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Roberts TD, Hutchinson DS, Wootten D, De Blasio MJ, Ritchie RH. Advances in incretin therapies for targeting cardiovascular disease in diabetes. J Mol Cell Cardiol 2025; 202:102-115. [PMID: 40086589 DOI: 10.1016/j.yjmcc.2025.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 02/12/2025] [Accepted: 03/11/2025] [Indexed: 03/16/2025]
Abstract
The global prevalence of obesity is skyrocketing at an alarming rate, with recent data estimating that one-in-eight people are now living with the disease. Obesity is a chronic metabolic disorder that shares underlying pathophysiology with other metabolically-linked diseases such as type 2 diabetes mellitus, cardiovascular disease and diabetic cardiomyopathy. There is a distinct correlation between type 2 diabetes status and the likelihood of heart failure. Of note, there is an apparent sexual dimorphism, with women disproportionately affected with respect to the degree of severity of the cardiac phenotype of diabetic cardiomyopathy that results from diabetes. The current pharmacotherapies available for the attenuation of hyperglycaemia in type 2 diabetes are not always effective, and have varying degrees of efficacy in the setting of heart failure. Insulin can worsen heart failure prognosis whereas metformin, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and more recently, glucagon-like peptide-1 receptor agonists (GLP-1RAs), have demonstrated cardioprotection with their administration. This review will highlight the advancement of incretin therapies for individuals with diabetes and heart failure and explore newly-reported evidence of the clinical usefulness of GLP-1R agonists in this distinct phenotype of heart failure.
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Affiliation(s)
- Timothy D Roberts
- Heart Failure Pharmacology Laboratory, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, VIC, Australia
| | - Dana S Hutchinson
- Metabolic G Protein-Coupled Receptor Laboratory, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, VIC, Australia
| | - Denise Wootten
- Metabolic G Protein-Coupled Receptor Laboratory, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, VIC, Australia; ARC Centre for Cryo-Electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia
| | - Miles J De Blasio
- Heart Failure Pharmacology Laboratory, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, VIC, Australia.
| | - Rebecca H Ritchie
- Heart Failure Pharmacology Laboratory, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, VIC, Australia.
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Shafiek MZ, Zaki HF, Mohamed AF, Ibrahim WW. Novel Trajectories Towards Possible Effects of Semaglutide for Amelioration of Reserpine-induced Fibromyalgia in Rats: Contribution of cAMP/PKA/p-CREB and M1/M2 Microglia Polarization. J Neuroimmune Pharmacol 2025; 20:43. [PMID: 40240584 PMCID: PMC12003577 DOI: 10.1007/s11481-025-10196-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Accepted: 03/20/2025] [Indexed: 04/18/2025]
Abstract
Fibromyalgia (FM) is a pain disorder characterized by pervasive musculoskeletal pain associated with exhaustion, depression, and irregular sleep patterns. Semaglutide, an innovative glucagon-like peptide-1 (GLP-1) agonist, has shown analgesic effects by modulating pain hypersensitivity in animal models of inflammatory pain. The objective of this study is to ascertain semaglutide's therapeutic potential against FM-like symptoms caused by reserpine. Reserpine (1 mg/kg/day; SC) was administered into rats for 3 consecutive days, then they were treated daily with semaglutide intraperitoneally in low (5 nmol/kg), intermediate (10 nmol/kg), or high doses (20 nmol/kg), respectively, for 14 consecutive days. Semaglutide alleviated reserpine induced histopathological and immunohistopathological changes in spinal cord of rats evidenced by a remarkable rise in immuno-expression of cluster of differentiation 163 (CD163) contrary to a significant diminution in CD86 level as compared with reserpine group. Semaglutide also had an analgesic effect and improved motor incoordination, and depression brought on by reserpine. Furthermore, it had an anti-inflammatory impact via stimulating cyclic adenosine monophosphate (cAMP)/ protein kinase A (PKA)/ cAMP response element (CRE)-binding protein (CREB) signaling pathway and shifting M1/M2 macrophage polarization towards the M2. Semaglutide's anti-inflammatory actions were manifested through inhibition of inducible nitric oxide synthase and reduction in dorsal root ganglia concentrations of tumor necrosis factor-α together with elevation in the levels of arginase-1 and interleukin-4.
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Affiliation(s)
- Mena Z Shafiek
- Department of Pharmacology and Toxicology, Faculty of Dentistry, Misr International University, Cairo, Egypt.
| | - Hala F Zaki
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
| | - Ahmed F Mohamed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
- Faculty of Pharmacy, King Salman International University (KSIU), South Sinai 46612, Sinai, Egypt
| | - Weam W Ibrahim
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
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3
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Liu T, Shi F, Guo Z, Li H, Qin D. Therapeutic Potential of the Novel GLP-1 Receptor Agonist Semaglutide in Alcohol Use Disorder. PHARMACOPSYCHIATRY 2025. [PMID: 40228539 DOI: 10.1055/a-2550-6470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/16/2025]
Abstract
Alcohol use disorder (AUD) is a prevalent neuropsychiatric disorder with serious health and social consequences. However, few licensed and successful pharmacotherapies exist for heterogeneous and complex disorders such as AUD, and these are poorly utilized. Preclinical and clinical findings suggest that the glucagon-like peptide-1 (GLP-1) system, a gut-brain peptide, is involved in the neurobiology of addictive behaviors. Additionally, the GLP-1 receptor (GLP-1R) has become a promising target for the treatment of AUD. Semaglutide, a novel GLP-1R agonist, has received clinical approval to treat type 2 diabetes in both subcutaneous and oral dosage forms. Studies have shown that it significantly reduces alcohol consumption and relapse of alcohol addiction in rats, suggesting its potential effectiveness for treating alcohol abuse in humans, particularly in overweight patients with AUDs. However, the use of semaglutide is associated with potential risks, such as gallbladder disease and clinical complications associated with delayed gastric emptying. This review evaluates the safety of semaglutide to inform its wider clinical application. Further extensive and in-depth studies on semaglutide are needed to reveal additional valuable clinical benefits.
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Affiliation(s)
- Tingting Liu
- School of Chemical Engineering, Changchun University of Technology, Changchun, China
| | - Fuqiang Shi
- School of Chemical Engineering, Changchun University of Technology, Changchun, China
| | - Zhihua Guo
- School of Chemical Engineering, Changchun University of Technology, Changchun, China
| | - Hongwu Li
- School of Chemical Engineering, Changchun University of Technology, Changchun, China
| | - Di Qin
- The Third Bethune Hospital of Jilin University, Changchun, China
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Gaddy A, Elrggal M, Madariaga H, Kelly A, Lerma E, Colbert GB. Diabetic Kidney Disease. Dis Mon 2025; 71:101848. [PMID: 39753456 DOI: 10.1016/j.disamonth.2024.101848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2025]
Abstract
Diabetic kidney disease is a leading cause of kidney failure worldwide and is easily detectable with screening examination. Diabetes causes hyperfiltration and activation of the renin-angiotensin aldosterone system by hemodynamic changes within the nephron, which perpetuates damaging physiology. Diagnosis is often clinical after detection of heavy proteinuria in a patient with diabetes,but can be confirmed by observation of histologic stages on kidney biopsy. Mainstays of treatment include angiotensin conversion or receptor blockade, mineralocorticoid receptor blockade, and tight glucose control. Newer agents favored in diabetic kidney disease are sodium glucose-cotransporters and glucagon-like peptide 1 receptor agonists, both for glycemic control and for various methods of reversing damaging physiology.
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Affiliation(s)
- Anna Gaddy
- Division of Nephrology, Medical College of Wisconsin, 8700 Watertown Plank Road Milwaukee, WI 53226, USA.
| | - Mohamed Elrggal
- Nephrology Department, Kidney and Urology Center, Alexandria, Egypt
| | | | - Adam Kelly
- Division of Nephrology, Medical College of Wisconsin, 8700 Watertown Plank Road Milwaukee, WI 53226, USA
| | - Edgar Lerma
- Section of Nephrology, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Gates B Colbert
- Division of Nephrology, Texas A&M University College of Medicine in Dallas, Dallas, TX 75246, USA
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Wang C, Wu Z, Zhou J, Cheng B, Huang Y. Semaglutide, a glucagon-like peptide-1 receptor agonist, inhibits oral squamous cell carcinoma growth through P38 MAPK signaling pathway. J Cancer Res Clin Oncol 2025; 151:103. [PMID: 40055197 PMCID: PMC11889073 DOI: 10.1007/s00432-025-06154-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Accepted: 02/26/2025] [Indexed: 03/12/2025]
Abstract
AIMS Researches have shown that diabetes mellitus (DM) can promote the risk and progression of oral squamous cell carcinoma (OSCC). Semaglutide, a glucagon-like peptide-1 receptor agonist, is currently employed to treat type 2 diabetes mellitus (T2DM) and obesity. This study intends to explore the potential effects and mechanism of Semaglutide on OSCC. METHODS The expression of GLP-1R in OSCC cells and tissues was evaluated by qRT-PCR, western blot and immunohistochemistry assays. Cell proliferation, invasion, migration and apoptosis abilities were determined by relevant experiments. Western blot was employed to verify the expression of relevant proteins and examine the effect of Semaglutide on the MAPK signaling pathway. The xenograft transplantation model of OSCC was established to examine the anti-cancer effects of Semaglutide in vivo and immunohistochemistry assays were performed on tumor tissues. RESULTS GLP-1R expression was elevated in OSCC cells and tissues as compared with that in normal. Semaglutide effectively inhibited the proliferation, migration and invasion of OSCC cells while concurrently promoting apoptosis. Moreover, Semaglutide specifically activated the P38 MAPK signaling pathway without significant influence on ERK1/2 or SAPK/JNK, and its pro-apoptotic effects in OSCC cells was related to P38 pathway activation. Animal experiments verified the inhibitory effect of Semaglutide on OSCC tumors in mice. CONCLUSIONS Semaglutide exerts inhibitory actions on OSCC and may induce apoptosis in OSCC cells via the P38 MAPK signaling pathway. This study has significant implications for the treatment of patients with diabetes who are also afflicted by OSCC.
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Affiliation(s)
- Can Wang
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, People's Republic of China
- Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510080, People's Republic of China
| | - Zhengzheng Wu
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, People's Republic of China
- Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510080, People's Republic of China
| | - Jiaying Zhou
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, People's Republic of China
- Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510080, People's Republic of China
| | - Bin Cheng
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, People's Republic of China.
- Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510080, People's Republic of China.
| | - Yulei Huang
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, People's Republic of China.
- Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510080, People's Republic of China.
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Xia L, Li H, Huang S, Shen L. Semaglutide vs. dulaglutide for glycemic and weight control in patients with type 2 diabetes mellitus: A systematic review and meta‑analysis. Biomed Rep 2025; 22:35. [PMID: 39781043 PMCID: PMC11704830 DOI: 10.3892/br.2024.1913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 11/04/2024] [Indexed: 01/11/2025] Open
Abstract
The present systematic review and meta-analysis aimed to evaluate the effectiveness of semaglutide and dulaglutide for glycemic control and weight loss in patients with type 2 diabetes mellitus (T2DM). A thorough literature search was conducted using several databases from inception until the end of July 2024. The primary outcome was the difference in glycated hemoglobin levels from the initial measurement between the groups. By contrast, the secondary outcome was the effect of the medications on body weight loss (change in body weight from baseline) during the treatment period. Appropriate statistical tests were employed to reach study endpoints. The results showed no statistically significant difference in glycemic control achievement between the two medications in patients with T2DM. Semaglutide demonstrated higher efficacy in inducing weight loss; however, sensitivity analysis indicated that the weight loss efficacy results should be interpreted cautiously. The study acknowledges the high heterogeneity and low quality among the studies included in the meta-analysis and the potential impact of individual studies on the outcome. Despite these limitations, the findings suggested that semaglutide may be a more favorable treatment option for patients with T2DM requiring weight management and glycemic control. Further research is needed to investigate the long-term benefits of glucagon-like peptide-1 receptor agonists and individual factors that may influence treatment response and outcomes.
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Affiliation(s)
- Lili Xia
- Department of Endocrinology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China
| | - Huihua Li
- Department of Endocrinology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China
| | - Shan Huang
- Department of Endocrinology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China
| | - Lisha Shen
- Department of Endocrinology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China
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Chun E, Siojo A, Rivera D, Reyna K, Legere H, Joseph R, Pojednic R. Weight loss and body composition after compounded semaglutide treatment in a real world setting. Diabetes Obes Metab 2025; 27:1536-1543. [PMID: 39776038 DOI: 10.1111/dom.16162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 12/09/2024] [Accepted: 12/18/2024] [Indexed: 01/11/2025]
Abstract
INTRODUCTION Clinical trials have shown efficacy of semaglutide for weight loss, but further study is needed in less controlled environments including impacts on body composition. MATERIALS AND METHODS This retrospective study included individuals who participated in a weight management programme at a commercial wellness studio receiving once-weekly compounded semaglutide/cyanocobalamin injections from June 2023 to January 2024. Once-weekly semaglutide/cyanocobalamin injected subcutaneously starting at 0.25 mg/0.125 mg and titrated to a maximum dose of 2.4 mg/0.24 mg. The primary endpoint was weight loss at 3 months, with secondary analyses including weight loss percentage, weight loss by body mass index (BMI) class and body composition changes including changes in total fat mass, lean body mass, skeletal muscle mass and trunk adiposity. RESULTS A total of 94 individuals were analysed (81F/13M), age in years mean (SD) = 46.57 (10.60). After 3 months, average weight loss was 4.11 (2.77) kg or 4.57% (2.96%). Individuals lost fat mass (2.67 (2.37) kg) and trunk fat mass (1.10 (1.36) kg), while also losing small amounts of lean mass (1.43 (1.41) kg) and skeletal muscle mass (0.88 (0.81) kg). As a proportion of total weight, fat mass decreased while lean muscle mass and skeletal muscle mass increased. DISCUSSION This study demonstrates that meaningful weight loss is achievable on semaglutide/cyanocobalamin outside of a closely controlled environment. In addition, body composition improved with losses in fat mass and gains in overall proportion of lean muscle and skeletal muscle.
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Affiliation(s)
- Elizabeth Chun
- Department of Statistics, Texas A&M University, College Station, Texas, USA
- Restore Hyper Wellness, Austin, Texas, USA
| | | | | | - Kirsten Reyna
- Restore Hyper Wellness, Austin, Texas, USA
- University of Connecticut, Storrs, Connecticut, USA
| | | | - Richard Joseph
- Restore Hyper Wellness, Austin, Texas, USA
- Division of Preventive Medicine, Mass General Brigham, Boston, Massachusetts, USA
| | - Rachele Pojednic
- Restore Hyper Wellness, Austin, Texas, USA
- Stanford Lifestyle Medicine, Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, California, USA
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Mather KJ, Mari A, Weerakkody G, Heise T, DeVries JH, Urva S, Coskun T, Milicevic Z, Haupt A, Thomas MK. Greater improvement in insulin sensitivity per unit weight loss associated with tirzepatide versus semaglutide: An exploratory analysis. Diabetes Obes Metab 2025; 27:1507-1514. [PMID: 39762971 DOI: 10.1111/dom.16159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 12/06/2024] [Accepted: 12/16/2024] [Indexed: 02/08/2025]
Abstract
AIMS To explore the relationship between weight loss and insulin sensitivity in response to tirzepatide or semaglutide. MATERIALS AND METHODS We conducted a post hoc exploratory analysis of a 28-week, double-blind, randomized trial in people with type 2 diabetes treated with metformin, randomized to tirzepatide 15 mg, semaglutide 1 mg or placebo. We evaluated the relationship between change in body weight and change in insulin sensitivity determined from hyperinsulinemic euglycemic clamp (M value), or from mixed-meal tolerance testing (Matsuda index). RESULTS Tirzepatide was associated with a greater improvement than semaglutide in insulin sensitivity assessed using hyperinsulinemic euglycemic clamps (p < 0.001). With tirzepatide, improvements in insulin sensitivity were associated with percent change in weight (R = -0.656, p < 0.0001). With semaglutide, change in insulin sensitivity was less strongly correlated with percent change in weight (R = -0.268, p = 0.0820; p = 0.0242 vs. tirzepatide). In regression analyses, the slope of the relationship between change in M value and change in weight was statistically different between semaglutide and tirzepatide (p = 0.0461). These relationships were also assessed using the Matsuda index as the metric of insulin sensitivity, and using change in fat mass as the determinant of change in insulin sensitivity. CONCLUSIONS Improvement in insulin sensitivity was proportional to weight and fat loss, with greater strength of association with tirzepatide. In regression analysis, tirzepatide was associated with greater improvement in insulin sensitivity per unit weight loss than semaglutide. The greater improvement in insulin sensitivity following treatment with tirzepatide was not simply attributable to greater weight or fat loss.
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Affiliation(s)
| | - Andrea Mari
- Institute of Neuroscience, National Research Council, Padova, Italy
| | | | | | | | - Shweta Urva
- Eli Lilly and Company, Indianapolis, Indiana, USA
| | - Tamer Coskun
- Eli Lilly and Company, Indianapolis, Indiana, USA
| | | | - Axel Haupt
- Eli Lilly and Company, Indianapolis, Indiana, USA
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Siamashvili M, Davis SN. Evaluating semaglutide + LAI-287 (IcoSema) for the treatment of diabetes mellitus type II. Expert Opin Pharmacother 2025; 26:1-7. [PMID: 39629799 DOI: 10.1080/14656566.2024.2436593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 11/27/2024] [Indexed: 12/17/2024]
Abstract
INTRODUCTION A stepwise coordinated multiple therapeutic targeted approach to the treatment of type 2 diabetes includes starting with lifestyle modification, oral antihyperglycemic agents, non-insulin injectables (Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and both short and long-acting insulins. Ultra-long-acting insulins offer more convenient administration. As in any chronic disease, the introduction of a novel medication must balance safety, efficacy, financial cost, as well as improved patient convenience and adherence. AREAS COVERED This manuscript describes IcoSema - a new investigational fixed-ratio combination of basal insulin icodec and the GLP-1 RA semaglutide. The key trials from the clinical development process of insulin icodec, semaglutide, and IcoSema are reviewed with important endpoints highlighted. EXPERT OPINION Once-weekly IcoSema offers glycemic efficacy that is non-inferior to glargine+aspart, similar risk of hypoglycemia, significant reduction in body weight, the convenience of use, and favorable safety profile with most adverse events being gastrointestinal.
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Affiliation(s)
- Maka Siamashvili
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Stephen N Davis
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
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Samanta A, Bordbar DD, Weng CY, Chancellor JR. Glucagon-like Peptide-1 Receptor Agonists in the Management of Diabetic Retinopathy. Int Ophthalmol Clin 2025; 65:23-26. [PMID: 39710901 DOI: 10.1097/iio.0000000000000541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2024]
Abstract
Glucagon-like peptide-1 (GLP-1) receptor agonists are a family of drugs, most well known by the third-generation once-weekly subcutaneous semaglutide, that act on the incretin pathway of metabolic, hormonal signaling to modulate pancreatic insulin release, gastric emptying, energy intake, and subjective feelings of satiety. This class of drugs' efficacy and safety in the treatment of type 2 diabetes and obesity have been demonstrated across multiple large randomized controlled trials. These data have propelled GLP-1 receptor agonists to ubiquity in diabetic management and weight loss therapy, leading them to be frequently encountered in ophthalmic practice. The effect of GLP-1 receptor agonists like semaglutide on diabetic retinopathy (DR) is at this point unclear; some studies indicate a worsening of DR with the initiation of GLP-1 agonists, especially semaglutide. Overall, the macrovascular reduction of cardiovascular and stroke risks from GLP-1 receptor agonists should be prioritized over the potential microvascular progression of DR, as long as the patient is regularly followed by ophthalmology.
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Affiliation(s)
- Anindya Samanta
- Cullen Eye Institute, Baylor College of Medicine, Houston, TX
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Fink-Jensen A, Wörtwein G, Klausen MK, Holst JJ, Hartmann B, Thomsen M, Ptito M, Beierschmitt A, Palmour RM. Effect of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide on alcohol consumption in alcohol-preferring male vervet monkeys. Psychopharmacology (Berl) 2025; 242:63-70. [PMID: 38884652 PMCID: PMC11742737 DOI: 10.1007/s00213-024-06637-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 05/20/2024] [Indexed: 06/18/2024]
Abstract
RATIONALE Glucagon-like peptide-1 (GLP-1) receptor agonists reduce alcohol consumption in rodents and non-human primates. Semaglutide is a new long-acting GLP-1 receptor agonist, widely used in the clinic against type 2 diabetes and obesity. It is also reported to reduce alcohol intake in rodents. OBJECTIVES This study investigates the possible inhibitory effect of semaglutide on alcohol intake in alcohol-preferring African green monkeys. METHODS We performed a vehicle-controlled study on male monkeys that had demonstrated a preference for alcohol. In the monkeys selected for voluntary alcohol drinking, alcohol consumption was measured for ten days at baseline (Monday to Friday for two weeks). During this period, the monkeys had access to alcohol 4 h per day and free access to water 24 h per day. After two weeks of baseline measurements, the monkeys were randomized to semaglutide or vehicle. Each group consisted of ten monkeys, and the two groups were balanced with respect to baseline alcohol intake. Following the baseline period, the monkeys were treated with escalating doses of semaglutide (up to 0.05 mg/kg) or vehicle subcutaneously twice weekly for two weeks during which period alcohol was not available. After uptitration, the monkeys had access to alcohol 4 h daily for 20 days (Monday to Friday for 4 weeks), and alcohol consumption was measured. During this alcohol exposure period, treatment with semaglutide (0.05 mg/kg twice weekly) or vehicle continued for three weeks followed by a one-week washout period. RESULTS Compared to the vehicle, semaglutide significantly reduced alcohol intake. There were no signs of emetic events or changes in water intake. CONCLUSIONS These data demonstrate for the first time the potent effect of semaglutide in reducing voluntary alcohol intake in non-human primates and further substantiate the need for clinical trials investigating the effect of semaglutide in patients with alcohol-use disorder.
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Affiliation(s)
- Anders Fink-Jensen
- Laboratory of Neuropsychiatry, Mental Health Centre Copenhagen, Mental Health Services in the Capital Region of Denmark, University of Copenhagen, Hovedvejen 17, Frederiksberg, DK-2000, Denmark.
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
| | - Gitta Wörtwein
- Laboratory of Neuropsychiatry, Mental Health Centre Copenhagen, Mental Health Services in the Capital Region of Denmark, University of Copenhagen, Hovedvejen 17, Frederiksberg, DK-2000, Denmark
- Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Mette Kruse Klausen
- Laboratory of Neuropsychiatry, Mental Health Centre Copenhagen, Mental Health Services in the Capital Region of Denmark, University of Copenhagen, Hovedvejen 17, Frederiksberg, DK-2000, Denmark
| | - Jens Juul Holst
- Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Bolette Hartmann
- Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Morgan Thomsen
- Laboratory of Neuropsychiatry, Mental Health Centre Copenhagen, Mental Health Services in the Capital Region of Denmark, University of Copenhagen, Hovedvejen 17, Frederiksberg, DK-2000, Denmark
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Maurice Ptito
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- School of Optometry, Université de Montréal, Montréal (Qc), Canada
| | - Amy Beierschmitt
- Behavioural Science Foundation, St. Kitts, Saint Kitts and Nevis
| | - Roberta M Palmour
- Behavioural Science Foundation, St. Kitts, Saint Kitts and Nevis
- Faculty of Medicine and Health Sciences, McGill University, Montréal (Qc), Canada
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Joshi N, Baloch KM, Rukh S, Khan AM, Muskan F, Kumari V, Khan H, Zeeshan M, Azam G, Khalid S, Anwar IB, Ahmed IF, Nishat SM, Gandhi F. Unlocking the potential of glucagon-like peptide-1 receptor agonists in revolutionizing type 2 diabetes management: a comprehensive review. Ann Med Surg (Lond) 2024; 86:7255-7264. [PMID: 39649934 PMCID: PMC11623894 DOI: 10.1097/ms9.0000000000002712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 10/25/2024] [Indexed: 12/11/2024] Open
Abstract
Diabetes mellitus (DM) is a long-term metabolic disorder caused by inadequate production and resistance to insulin. The prevalence of DM is rapidly increasing, with type 2 diabetes (T2D) accounting for more than 90% of cases. Despite new treatments, many patients with T2D do not meet their glycemic targets due to clinical inertia. This review provides an overview of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in the management of T2D. The review synthesizes data from clinical trials and meta-analyses on the efficacy, safety, and cost-effectiveness of GLP-1 RAs. It also discusses the mechanisms of action, classification, and barriers to adherence and persistence in therapy. GLP-1 RAs improve glycemic control by lowering A1C levels and promoting weight loss. They have cardioprotective effects and may reduce endothelial inflammation, oxidative stress, and blood pressure. Adherence to GLP-1 RAs is better with once-weekly injections, though gastrointestinal side effects and cost can affect persistence. Semaglutide and liraglutide have shown significant weight reduction, with semaglutide being particularly effective. GLP-1 RAs are cost-effective due to reduced healthcare costs associated with fewer hospitalizations and lower mortality rates. Safety concerns include gastrointestinal issues, pancreatitis, and rare cases of diabetic retinopathy and thyroid C-cell tumors. For clinical practice, GLP-1 RAs represent a valuable option not only for glycemic control but also for weight management and cardiovascular protection. Incorporating GLP-1 RAs into treatment plans can improve patient outcomes, and optimizing dosing regimens and addressing barriers such as cost and side effects are crucial to enhancing patient adherence and long-term treatment success.
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Affiliation(s)
- Nandan Joshi
- Department of Internal Medicine, Surat Municipal Institute of Medical Education and Research, Surat, India
| | - Kanwal Mir Baloch
- Department of Internal Medicine, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan
| | - Shah Rukh
- Department of Internal Medicine, Jinnah Sindh Medical University, Karachi, Pakistan
| | - Abdul Moiz Khan
- Department of Internal Medicine, Sahiwal Medical College, Sahiwal, Pakistan
| | - Fnu Muskan
- Department of Internal Medicine, Khairpur Medical College, Khairpur, Pakistan
| | - Verkha Kumari
- Department of Internal Medicine, Liaquat National Hospital and Medical College, Karachi, Pakistan
| | - Hasher Khan
- Department of Internal Medicine, Dow Medical College, Karachi, Pakistan
| | - Mohd Zeeshan
- Department of Internal Medicine, Career Institute of Medical Sciences and Hospital, Lucknow, India
| | - Ghufran Azam
- Department of Internal Medicine, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan
| | - Saif Khalid
- Department of Internal Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Insa Binte Anwar
- Department of Internal Medicine, Liaquat National Hospital and Medical College, Karachi, Pakistan
| | - Iqra Furqan Ahmed
- Department of Internal Medicine, Liaquat National Hospital and Medical College, Karachi, Pakistan
| | - Syeed Mahmud Nishat
- Department of Internal Medicine, Shaheed Suhrawardy Medical College, Dhaka, Bangladesh
| | - Fenil Gandhi
- Department of Family Medicine, PGY2, Lower Bucks Hospital, Bristol, PA, USA
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Tian X, Wang W, Zhang L, Wang L, Zhang K, Ge X, Luo Z, Zhao Y, Zhai X, Li C. Acupuncture and Drug Combination Therapy for Abnormal Glucose Metabolism: Exploring Synergistic Enhancement and Reduced Toxicity Mechanisms. Diabetes Metab Syndr Obes 2024; 17:4525-4537. [PMID: 39624791 PMCID: PMC11611509 DOI: 10.2147/dmso.s492626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 11/16/2024] [Indexed: 01/03/2025] Open
Abstract
This review examines the impact of combining acupuncture with drug therapy on abnormal glucose metabolism and investigates their underlying mechanisms. Conditions like diabetes pose significant health risks due to irregular glucose metabolism. Traditional drug treatments often encounter challenges related to side effects and drug resistance. Acupuncture, as a non-pharmacological intervention, is thought to enhance glucose metabolism and mitigate medication side effects. We selected the relevant studies of acupuncture or electroacupuncture combined with drugs in the treatment of abnormal glucose metabolism in the past five years, and the results indicate that the combination of acupuncture or electroacupuncture and drug therapy markedly enhances glucose metabolism and mitigates medication-related side effects such as gastrointestinal discomfort and hypoglycemia. Overall, this review underscores the synergistic benefits of acupuncture and drug therapy in improving treatment efficacy and reducing adverse effects, offering promising new approaches for managing abnormal glucose metabolism. Our review provides evidence for the potential benefits of combining acupuncture with drug therapy for abnormal glucose metabolism, which could lead to improved treatment outcomes and reduced side effects for patients with type 2 diabetes mellitus.
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Affiliation(s)
- Xinyi Tian
- School of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China
| | - Wenjun Wang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China
| | - Lu Zhang
- Graduate School, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China
| | - Liuqing Wang
- Institute of Chinese Medical History and Literatures, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China
| | - Kaiqi Zhang
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China
| | - Xiaolei Ge
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China
| | - Zhengrong Luo
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China
| | - Yaqian Zhao
- School of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China
| | - Xu Zhai
- Graduate School, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China
| | - Chunjing Li
- School of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China
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14
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Kamal N, Lee K, Aleppo G. Newer Outpatient Diabetes Therapies and Technologies. Med Clin North Am 2024; 108:923-951. [PMID: 39084842 DOI: 10.1016/j.mcna.2024.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
New diabetes drugs such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and glucose-dependent insulinotropic peptide/GLP-1 RAs have emerged to show hemoglobin A1c (HbA1c) reduction, weight loss, and cardiovascular benefits. Similarly, sodium-glucose cotransporter 2 inhibitors' benefits span from HbA1c decrease to cardiovascular and renoprotective effects. Diabetes technology has expanded to include type 2 diabetes mellitus, with literature supporting its use in T2DM on any insulin regimen. Connected insulin pens and insulin delivery devices have opened new solutions to insulin users and automated insulin delivery systems have become the standard of care therapy for type 1 diabetes mellitus.
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Affiliation(s)
- Nevin Kamal
- Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, 645 North Michigan Avenue, Suite 530, Chicago, IL, USA
| | - Kristen Lee
- Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, 645 North Michigan Avenue, Suite 530, Chicago, IL, USA
| | - Grazia Aleppo
- Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, 645 North Michigan Avenue, Suite 530, Chicago, IL, USA.
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Trott M, Arnautovska U, Siskind D. GLP-1 receptor agonists and weight loss in schizophrenia - past, present, and future. Curr Opin Psychiatry 2024; 37:363-369. [PMID: 38847529 DOI: 10.1097/yco.0000000000000952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
PURPOSE OF REVIEW People with schizophrenia experience three to five times higher prevalence of diabetes and obesity than the general population, contributing to a 20-year reduced lifespan. The impacts of weight gain extend beyond physical health, affecting people's self-esteem, quality of life, and triggering treatment nonadherence, leading to relapse and deteriorations in health. Clinical guidelines recommend patients with antipsychotic-induced weight gain are treated with cognitive behaviour therapy and lifestyle changes; however, effective treatments for obesity in schizophrenia are critically lacking. Glucagon-like peptide-1 receptor agonists (GLP-RAs) have shown large effects in weight loss in the general population; however, effects are less clear in people with schizophrenia. This review aims to assess the clinical trials that have been completed, are in progress, and directions for future trials. RECENT FINDINGS To date, six clinical trials have been completed, four of which have published their findings. Three further trials are currently in progress. SUMMARY Results from completed trials suggest that GLP-1RAs decrease weight in people with schizophrenia, however effect sizes are mostly smaller than studies based on the general population. Future trials could focus on dual or triple agonist agents, and/or explore the effects of GLP-1 s at antipsychotic medication commencement, to potentially prevent antipsychotic weight gain.
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Affiliation(s)
- Mike Trott
- Faculty of Medicine, The University of Queensland, Brisbane
- Queensland Centre for Mental Health Research, Wacol
- Metro South Addiction and Mental Health Service, Brisbane, Queensland, Australia
| | - Urska Arnautovska
- Faculty of Medicine, The University of Queensland, Brisbane
- Queensland Centre for Mental Health Research, Wacol
- Metro South Addiction and Mental Health Service, Brisbane, Queensland, Australia
| | - Dan Siskind
- Faculty of Medicine, The University of Queensland, Brisbane
- Queensland Centre for Mental Health Research, Wacol
- Metro South Addiction and Mental Health Service, Brisbane, Queensland, Australia
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16
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Anson M, Henney AE, Broadwell N, Zhao SS, Ibarburu GH, Lip GYH, Wilding JPH, Cuthbertson DJ, Alam U. Incidence of new onset type 2 diabetes in adults living with obesity treated with tirzepatide or semaglutide: real world evidence from an international retrospective cohort study. EClinicalMedicine 2024; 75:102777. [PMID: 39246719 PMCID: PMC11377141 DOI: 10.1016/j.eclinm.2024.102777] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 07/20/2024] [Accepted: 07/22/2024] [Indexed: 09/10/2024] Open
Abstract
Background Tirzepatide, a novel dual agonist of glucagon-like-peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), has demonstrated greater magnitude of weight loss compared to semaglutide in a phase 3 clinical trial. However, the effect of tirzepatide on incidence of type 2 diabetes (T2D) in individuals with overweight and obesity, and the effect on major adverse cardiovascular outcomes in individuals with pre-existing T2D, remains unknown. Methods We performed a retrospective cohort study of anonymised electronic medical records using the TriNetX network (TriNetX LLC, Cambridge, MA, USA) a global federated database. The data used in this study was collected on 5th June 2024. Two cohorts of individuals were generated: 1) without pre-existing T2D and, 2) with T2D. We adopted an active comparator new user design on new initiations of either tirzepatide or semaglutide therapy. Analysis began from the index event which was defined as individuals on respective therapy for 6 months only. Analysis of outcomes was conducted off-drug, in individuals without a pre-existing history of the disease of interest. Individuals were followed up for 12 months post the index event. Primary outcome for cohort 1 was incidence of T2D, and for cohort 2 was composite: all-cause mortality, cerebral infarction, acute coronary syndrome, and heart failure. Secondary outcomes for cohort 1 were change in HbA1c and body weight and for cohort 2: incidence of micro- and macrovascular complications, suicidal ideation and/or attempt, and all-cause mortality. We propensity score matched (1:1) for potential confounders: baseline demographics, socioeconomic circumstances, HbA1c, weight, relevant co-morbidities, and anti-obesity, hypoglycaemic and cardioprotective agents. Findings The study population without T2D consisted of 13,846 individuals, equally split between tirzepatide and semaglutide users. Tirzepatide was associated with both lower risk for incident T2D (HR 0.73, 95% CI 0.58-0.92, p < 0.001) and greater weight loss (-7.7 kg, [95% CI -6.8, -8.5 kg], p < 0.001), compared to semaglutide (-4.8 kg, [95% CI -3.9, -5.6 kg], p < 0.001). In individuals with pre-existing T2D (n = 8446), tirzepatide was associated with lower risk of the composite outcome (HR 0.54, 95% CI 0.38-0.76, p < 0.001), cerebral infarction (HR 0.45, 95% CI 0.24-0.84, p = 0.010) and all-cause mortality (HR 0.33, 95% CI 0.15-0.73, p = 0.004) compared to semaglutide. Interpretation Tirzepatide is associated with significantly reduced risk of developing T2D and major adverse cardiovascular events in individuals living with obesity and T2D respectively. Randomised controlled trials investigating the utility of dual incretin agonists in the primary prevention of T2D and cardiovascular disease in higher risk populations are now required. Funding Nil.
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Affiliation(s)
- Matthew Anson
- Diabetes & Endocrinology Research, Institute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, UK
| | - Alex E Henney
- Diabetes & Endocrinology Research, Institute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, UK
| | | | - Sizheng S Zhao
- Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biological Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | | | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK
- Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - John P H Wilding
- Diabetes & Endocrinology Research, Institute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, UK
| | - Daniel J Cuthbertson
- Diabetes & Endocrinology Research, Institute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, UK
| | - Uazman Alam
- Diabetes & Endocrinology Research, Institute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, UK
- Visiting Fellow, Centre for Biomechanics and Rehabilitation Technologies, Staffordshire University, Stoke-on-Trent, UK
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17
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Alenzi S, Alzahrani A, Aljaloud A, Alanazi K, Alarfaj SJ. The effectiveness of 0.5 mg and 1mg of semaglutide in patients with type two diabetes and predictors of response: a retrospective cohort study. Front Endocrinol (Lausanne) 2024; 15:1395651. [PMID: 39205685 PMCID: PMC11349510 DOI: 10.3389/fendo.2024.1395651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Accepted: 07/08/2024] [Indexed: 09/04/2024] Open
Abstract
Background Semaglutide is a glucagon-like peptide-1 receptor agonists (GLP-1-RAs) approved for the treatment of type 2 diabetes mellitus (T2DM) at doses up to 1 mg. The results from randomized control trials and real-world studies revealed that weekly semaglutide was associated with significant improvements in HbA1c and body weight. To our knowledge, no study assessed the effectiveness of using semaglutide for patients with T2DM in the Saudi population. We aim to assess the effectiveness of once weekly SC 0.5 and 1 mg of semaglutide on HbA1c and weight reduction in patients with T2DM in the Saudi population within 12 months of use, evaluate the predictors of response, and compare the effect of the two doses. Method This is a retrospective cohort study conducted at Security Force Hospital in Riyadh, Saudi Arabia. Using electronic medical records of patients with type two diabetes who received semaglutide 0.5 or 1 mg for a total duration of at least 12 months of use. Results Within the study period of semaglutide use, HbA1c significantly decreased from baseline by -2.1% (-2.3 to -1.91, 95% CI) (P <0.001). While the mean change in weight was -6.19 kg (-6.66 to -5.72, 95% CI) (P<0.001). Moreover, BMI, FBG, total cholesterol, LDL, and TG all decreased significantly from baseline (p<0.001). When comparing the sub-groups of 0.5 and 1 mg doses, although results were numerically favorable of 1 mg, there were no statistically significant differences in HbA1c % (-2.1 ± 1.8 vs. -2.1 ± 1.9, p-value= 0.934, respectively), and weight (-6.1 ± 5 vs. -6.2 ± 4.4 kg, p-value=0.837, respectively). Significant predictors of HbA1c reduction were the duration of DM, baseline HbA1c, and insulin therapy. While the significant predictor for weight reduction was insulin therapy. Conclusion This study is document the effectiveness of once-weekly SC semaglutide on glycemic control and weight loss in real-world practice. We recommend a starting goal dose of 0.5 mg and gradual increase of dose based individual patient response. further studies are needed to assess the effectiveness and tolerability of various semagltude doses.
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Affiliation(s)
- Sara Alenzi
- Department of Pharmacy Practice, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Abdullah Alzahrani
- Department of Pharmaceutical Services, Security Forces Hospital Program, Riyadh, Saudi Arabia
| | - Afnan Aljaloud
- Department of Pharmaceutical Services, Security Forces Hospital Program, Riyadh, Saudi Arabia
| | - Kamayel Alanazi
- Department of Pharmaceutical Services, Security Forces Hospital Program, Riyadh, Saudi Arabia
| | - Sumaiah J. Alarfaj
- Department of Pharmacy Practice, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
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Golubic R, Kennet J, Parker V, Robertson D, Luo D, Hansen L, Jermutus L, Ambery P, Ryaboshapkina M, Surakala M, Laker RC, Venables M, Koulman A, Park A, Evans M. Dual glucagon-like peptide-1 and glucagon receptor agonism reduces energy intake in type 2 diabetes with obesity. Diabetes Obes Metab 2024; 26:2634-2644. [PMID: 38562018 DOI: 10.1111/dom.15579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 03/14/2024] [Accepted: 03/17/2024] [Indexed: 04/04/2024]
Abstract
AIMS To establish which components of energy balance mediate the clinically significant weight loss demonstrated with use of cotadutide, a glucagon-like peptide-1 (GLP-1)/glucagon receptor dual agonist, in early-phase studies. MATERIALS AND METHODS We conducted a phase 2a, single-centre, randomized, placebo-controlled trial in overweight and obese adults with type 2 diabetes. Following a 16-day single-blind placebo run-in, participants were randomized 2:1 to double-blind 42-day subcutaneous treatment with cotadutide (100-300 μg daily) or placebo. The primary outcome was percentage weight change. Secondary outcomes included change in energy intake (EI) and energy expenditure (EE). RESULTS A total of 12 participants (63%) in the cotadutide group and seven (78%) in the placebo group completed the study. The mean (90% confidence interval [CI]) weight change was -4.0% (-4.9%, -3.1%) and -1.4% (-2.7%, -0.1%) for the cotadutide and placebo groups, respectively (p = 0.011). EI was lower with cotadutide versus placebo (-41.3% [-66.7, -15.9]; p = 0.011). Difference in EE (per kJ/kg lean body mass) for cotadutide versus placebo was 1.0% (90% CI -8.4, 10.4; p = 0.784), assessed by doubly labelled water, and -6.5% (90% CI -9.3, -3.7; p < 0.001), assessed by indirect calorimetry. CONCLUSION Weight loss with cotadutide is primarily driven by reduced EI, with relatively small compensatory changes in EE.
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Affiliation(s)
- Rajna Golubic
- Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
- Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK
| | - Jane Kennet
- Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
| | - Victoria Parker
- Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
| | - Darren Robertson
- Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
| | - Dan Luo
- Statistics, Biometrics Oncology, Oncology R&D, AstraZeneca, Gaithersburg, Maryland, USA
| | - Lars Hansen
- Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA
| | - Lutz Jermutus
- Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
| | - Phil Ambery
- Late Clinical Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Maria Ryaboshapkina
- Translational Science and Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | | | - Rhianna C Laker
- Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA
| | | | - Albert Koulman
- MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
| | - Adrian Park
- Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
| | - Mark Evans
- Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
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Niu K, Fan M, Gao W, Chen C, Dai G. Adverse events in different administration routes of semaglutide: a pharmacovigilance study based on the FDA adverse event reporting system. Front Pharmacol 2024; 15:1414268. [PMID: 38887555 PMCID: PMC11180901 DOI: 10.3389/fphar.2024.1414268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 05/13/2024] [Indexed: 06/20/2024] Open
Abstract
Background With the continuously increasing incidence of type 2 diabetes, glucagon-like peptide-1 (GLP-1) receptor agonists, known for their dual benefits of effectively controlling blood glucose levels while also reducing weight and lowering cardiovascular disease risks, have been widely employed in the treatment of this condition. In recent years, semaglutide has garnered significant attention as the only injectable and orally administered glucagon-like peptide-1 receptor agonist (GLP-1RA). However, it is important to note that different routes of administration may lead to varying adverse events in patients. The aim of this study is to compare the adverse event profiles of semaglutide across different routes of administration by analyzing the adverse event reporting system of the U.S. Food and Drug Administration (FDA). The findings from this analysis will provide valuable insights for clinical practice and drug surveillance. Methods Data was extracted from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, specifically focusing on the period from the fourth quarter of 2017 to the fourth quarter of 2023. A comparative analysis was conducted using disproportionality analysis, reporting odds ratio (ROR), and stratified analysis methods to assess and compare the signals of adverse events (AE) and the time to onset of adverse reactions associated with different routes of administration of semaglutide from 2017 to 2023. Results A total of 22,287 adverse reaction records related to semaglutide were identified in the FAERS database. A comparative analysis was performed on 16,346 records of subcutaneous administration and 2,496 records of oral administration. Different routes of administration can lead to varying adverse reaction outcomes. Compared to oral administration, subcutaneous injection is more likely to result in adverse events related to the endocrine system. Oral administration is more likely to induce adverse events in the gastrointestinal system. Additionally, it significantly accelerates the onset of adverse reactions. The comparative analysis of all relevant results indicates that semaglutide can lead to different adverse reaction events depending on the route of administration. Furthermore, there are significant differences in the time of onset for these adverse reactions. Conclusion Semaglutide exhibits variations in adverse reaction events and the time of onset across different routes of administration. Therefore, when selecting the route of administration for semaglutide, clinicians should consider the risk of adverse events and weigh them against the clinical benefits. Based on these considerations, appropriate guidance and recommendations can be provided to patients.
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Affiliation(s)
- Kaibin Niu
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Maoxia Fan
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Wulin Gao
- Department of Geriatric Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Chen Chen
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Guohua Dai
- Department of Geriatric Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
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20
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Huang X, Wu M, Lin J, Mou L, Zhang Y, Jiang J. Gastrointestinal safety evaluation of semaglutide for the treatment of type 2 diabetes mellitus: A meta-analysis. Medicine (Baltimore) 2024; 103:e38236. [PMID: 38787986 PMCID: PMC11124640 DOI: 10.1097/md.0000000000038236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 04/24/2024] [Indexed: 05/26/2024] Open
Abstract
BACKGROUND Semaglutide, as an innovative weekly formulation, has attracted much attention. Nevertheless, the predominant occurrence of gastrointestinal adverse events (GIAEs) poses a noteworthy challenge linked to the use of this medication, substantially affecting its clinical applicability and the overall well-being of patients. Therefore, this systematic review aims to comprehensively discuss the GIAEs, providing a basis for clinical therapeutic decisions. METHODS We systematically searched 4 independent databases for randomized controlled trials investigating the application of semaglutide in managing type 2 diabetes mellitus. The search period spanned from the inception of the databases to December 2023. We conducted a comprehensive meta-analysis, employing Review Manager 5.4.1 software, to systematically analyze and evaluate potential biases. Our primary emphasis was on assessing the gastrointestinal safety profile of semaglutide. RESULTS The outcomes unveiled a noteworthy rise in the collective occurrence of GIAEs across all dosage groups of semaglutide in comparison with the control group (P < .05). Upon further analysis, it was observed that semaglutide showed a heightened occurrence of GIAEs in contrast to the placebo. However, statistically significant distinction was not observed when compared to the reduction of conventional doses or the transition to other types of glucagon-like peptide-1 receptor agonist. Additionally, an extended treatment duration with semaglutide (>30 weeks) demonstrated an association with a certain degree of decrease in the incidence of gastrointestinal events. Funnel plot assessment for publication bias demonstrated high-quality inclusion of studies with no apparent publication bias. CONCLUSION The frequency of GIAEs in using semaglutide was observed to be elevated in comparison to the control group. However, it was comparable to other glucagon-like peptide-1 receptor agonist or low-dose treatment regimens. Additionally, an extended treatment duration played a role in decreasing the frequency of GIAEs. These findings provide valuable insights for clinical practice. Nonetheless, further research is crucial to explore supplementary data indicators, informing clinical practices and better serving the interests of patients.
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Affiliation(s)
- Xiaoyan Huang
- Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Fujian, China
| | - Miaohui Wu
- School of Pharmacy, Fujian Medical University, Fujian, China
| | - Jiaojiao Lin
- Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Fujian, China
| | - Lunpan Mou
- Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Fujian, China
| | - Yaping Zhang
- Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Fujian, China
| | - Jianjia Jiang
- Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Fujian, China
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Natale F, Luisi E, Franzese R, Mollo N, Solimene A, Caso VM, Corvino A, Golino P, Cimmino G. Semaglutide in Cardiometabolic Diseases: SELECTing the Target Population. J Cardiovasc Dev Dis 2024; 11:145. [PMID: 38786967 PMCID: PMC11122593 DOI: 10.3390/jcdd11050145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 05/01/2024] [Accepted: 05/04/2024] [Indexed: 05/25/2024] Open
Abstract
Cardiovascular diseases remain the main cause of death and disability worldwide. Despite the tremendous improvement in pharmacological, minimally invasive and rehabilitative strategies, global deaths due to cardiovascular diseases are still increasing. Additional risk factors have been recently proposed, and thanks to scientific progress, novel drugs for the control of the main risk factors focusing on the cardiometabolic pathways have been identified. Glucagon-like peptide-1 (GLP-1) receptor agonists represent an innovative step in the management of patients affected by type 2 diabetes mellitus. In addition to their significant efficacy on glycemic homeostasis, some members of this class of drugs have indications in the treatment of obesity. Furthermore, accumulated evidence in the literature has finally suggested a protective role in cardiovascular health. The possible role of GLP-1R agonist drugs (GLP-1RAs) on the mechanisms underlying chronic inflammation and the almost ubiquitous distribution of GLP-1 receptors could explain the enormous versatility of these drugs. Semaglutide is a GLP-1RA recently proven to be effective in cardiovascular outcomes. In the present article, we will review the available data on semaglutide in light of the most recent publications to better characterize the target population achieving cardiovascular benefits.
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Affiliation(s)
- Francesco Natale
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy; (F.N.); (P.G.)
| | - Ettore Luisi
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy; (F.N.); (P.G.)
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Rosa Franzese
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy; (F.N.); (P.G.)
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Noemi Mollo
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy; (F.N.); (P.G.)
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Achille Solimene
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy; (F.N.); (P.G.)
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Valentina Maria Caso
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
- Pharmacy Unit, Monaldi Hospital, 80131 Naples, Italy
| | | | - Paolo Golino
- Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy; (F.N.); (P.G.)
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
| | - Giovanni Cimmino
- Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy
- Cardiology Unit, AOU Luigi Vanvitelli, 80138 Naples, Italy
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Balcázar-Valencia CM, García-Ramos AF, Osorio-Toro LM, Ordoñez-Guzmán YA, Buitrago-Gómez N, Cabarcas-López WF, Vizcaino-Guerrero CJ, Daza-Arana JE, Ramírez-Rincón A, Restrepo-Erazo K. Semaglutide Effects on Metabolic Outcomes in Diabetes Mellitus Patients - Real World Study. Diabetes Metab Syndr Obes 2024; 17:1667-1673. [PMID: 38616987 PMCID: PMC11016261 DOI: 10.2147/dmso.s443115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 01/11/2024] [Indexed: 04/16/2024] Open
Abstract
Purpose Diabetes is a public health problem that requires strategies to impact glycemic control and reduce the risk of long-term medical complications. Pharmacological management is a necessary treatment for this disease. Therefore, semaglutide is an essential tool to achieve the treatment targets. The present study aimed to evaluate the semaglutide effects on a cohort with type 2 diabetes mellitus (T2DM) in Colombia. Materials and Methods The cohort included 49 patients with T2DM that have been treated in a specialized care center. Their glycemic outcomes, weight, renal function, and adverse events were evaluated through a 3-, 6- and 12-month follow-up. Results Significant differences were observed in the outcome evaluation: reduction of glycated hemoglobin levels (MD -2.74 CI -1.95 to -3.52 in 6 months), fasting plasma glucose levels, body weight (MD -7.11 CI -5.97 to -8.24), and the albumin-to-creatinine ratio. The results were maintained throughout the treatment period. The adverse event rate was 16.3%, predominating gastrointestinal events. Conclusion This real-world evidence shows the efficacy of semaglutide in achieving treatment goals in patients with T2DM.
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Affiliation(s)
| | - Andrés Felipe García-Ramos
- Specialization in Internal Medicine, Faculty of Health, Universidad Santiago de Cali, Santiago de Cali, Colombia
- Research and Education Department, Clínica de Occidente S.A., Santiago de Cali, Colombia
- Specialization in Endocrinology, Faculty of Health Sciences, Universidad Pontificia Bolivariana, Medellín, Colombia
- Specialization in Internal Medicine, Faculty of Health, Universidad del Valle, Santiago de Cali, Colombia
| | - Luis Miguel Osorio-Toro
- Specialization in Internal Medicine, Faculty of Health, Universidad Santiago de Cali, Santiago de Cali, Colombia
- Research and Education Department, Clínica de Occidente S.A., Santiago de Cali, Colombia
- Genetics, Physiology and Metabolism Research Group (GEFIME), Faculty of Health Sciences, Universidad Santiago de Cali, Santiago de Cali, Colombia
| | | | - Nathalia Buitrago-Gómez
- Specialization in Endocrinology, Faculty of Health Sciences, Universidad Pontificia Bolivariana, Medellín, Colombia
| | | | | | - Jorge Enrique Daza-Arana
- Specialization in Internal Medicine, Faculty of Health, Universidad Santiago de Cali, Santiago de Cali, Colombia
- Health and Movement Research Group, Faculty of Health Sciences, Universidad Santiago de Cali, Santiago de Cali, Colombia
| | - Alex Ramírez-Rincón
- Specialization in Endocrinology, Faculty of Health Sciences, Universidad Pontificia Bolivariana, Medellín, Colombia
| | - Katherine Restrepo-Erazo
- Specialization in Internal Medicine, Faculty of Health, Universidad Santiago de Cali, Santiago de Cali, Colombia
- Specialization in Endocrinology, Faculty of Health, Universidad Nacional de Colombia, Bogotá D.C., Colombia
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23
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Wester A, Shang Y, Toresson Grip E, Matthews AA, Hagström H. Glucagon-like peptide-1 receptor agonists and risk of major adverse liver outcomes in patients with chronic liver disease and type 2 diabetes. Gut 2024; 73:835-843. [PMID: 38253482 PMCID: PMC11041618 DOI: 10.1136/gutjnl-2023-330962] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 01/13/2024] [Indexed: 01/24/2024]
Abstract
OBJECTIVE Phase II trials suggest glucagon-like peptide-1 receptor (GLP1) agonists resolve metabolic dysfunction-associated steatohepatitis but do not affect fibrosis regression. We aimed to determine the long-term causal effect of GLP1 agonists on the risk of major adverse liver outcomes (MALO) in patients with any chronic liver disease and type 2 diabetes. DESIGN We used observational data from Swedish healthcare registers 2010-2020 to emulate a target trial of GLP1 agonists in eligible patients with chronic liver disease and type 2 diabetes. We used an inverse-probability weighted marginal structural model to compare parametric estimates of 10-year MALO risk (decompensated cirrhosis, hepatocellular carcinoma, liver transplantation or MALO-related death) in initiators of GLP1 agonists with non-initiators. We randomly sampled 5% of the non-initiators to increase computational efficiency. RESULTS GLP1 agonist initiators had a 10-year risk of MALO at 13.3% (42/1026) vs 14.6% in non-initiators (1079/15 633) in intention-to-treat analysis (risk ratio (RR)=0.91, 95% CI=0.50 to 1.32). The corresponding 10-year per-protocol risk estimates were 7.4% (22/1026) and 14.4% (1079/15 633), respectively (RR=0.51, 95% CI=0.14 to 0.88). The per-protocol risk estimates at 6 years were 5.4% (21/1026) vs 9.0% (933/15 633) (RR=0.60, 95% CI=0.29 to 0.90) and at 8 years 7.2% (22/1026) vs 11.7% (1036/15 633) (RR=0.61, 95% CI=0.21 to 1.01). CONCLUSION In patients with chronic liver disease and type 2 diabetes who adhered to therapy over time, GLP1 agonists may result in lower risk of MALO. This suggests that GLP1 agonists are promising agents to reduce risk of chronic liver disease progression in patients with concurrent type 2 diabetes, although this needs to be corroborated in randomised trials.
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Affiliation(s)
- Axel Wester
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Ying Shang
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Emilie Toresson Grip
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
- Quantify Research, Stockholm, Sweden
| | - Anthony A Matthews
- Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Hannes Hagström
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
- Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden
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Tobaiqy M, Elkout H. Psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide: a pharmacovigilance analysis of individual case safety reports submitted to the EudraVigilance database. Int J Clin Pharm 2024; 46:488-495. [PMID: 38265519 PMCID: PMC10960895 DOI: 10.1007/s11096-023-01694-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 12/18/2023] [Indexed: 01/25/2024]
Abstract
BACKGROUND Semaglutide, liraglutide and tirzepatide are glucagon-like peptide-1 (GLP-1) receptor agonists that are effective for weight reduction. Recent reports of patients experiencing suicidal thoughts and other psychiatric adverse events while using GLP-1 agonists have raised concerns about the potential risk of self-harm and led the European Medicines Agency to investigate these medications. AIM To identify and analyse the psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide. METHOD All individual case safety reports for semaglutide, liraglutide, and tirzepatide reported to the EudraVigilance database from 01/01/2021 to 30/05/2023 were analysed. Descriptive statistics were used to explore study population characteristics. RESULTS During the study period, 31,444 adverse event reports were identified: semaglutide (n = 13,956; 44.4%), liraglutide (n = 16,748; 53.2%), and tirzepatide (n = 740; 2.3%). There were 372 reports with psychiatric adverse event reports (n = 372; 1.18%) with a total of 481 adverse events. Women accounted for 65% (n = 242) of these reports. Depression was the most commonly reported adverse event (n = 187; 50.3%), followed by anxiety (n = 144; 38.7%) and suicidal ideation (n = 73; 19.6%). Nine deaths (8 with liraglutide and 1 with semaglutide) and 11 life-threatening outcomes (4 associated with liraglutide and 7 with semaglutide) were reported. The fatal outcomes occurred primarily among men (8 out of 9) resulting from completed suicidal attempts and depression. CONCLUSION Psychiatric adverse events comprised only 1.2% of the total reports for semaglutide, liraglutide, and tirzepatide. However, the severity and fatal outcomes of some of these reports warrant further investigation.
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Affiliation(s)
- Mansour Tobaiqy
- Department of Pharmacology, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia.
| | - Hajer Elkout
- Department of Family and Community Medicine, Medical Faculty, University of Tripoli, Tripoli, 13275, Libya
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Gaw CE, Hays HL, Kemp CA, Kistamgari S, Spiller HA, Rine NI, Rhodes AL, Zhu M, Smith GA. Glucagon-Like Peptide-1 Receptor Agonist Cases Reported to United States Poison Centers, 2017-2022. J Med Toxicol 2024; 20:193-204. [PMID: 38421490 PMCID: PMC10959851 DOI: 10.1007/s13181-024-00999-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 02/12/2024] [Accepted: 02/14/2024] [Indexed: 03/02/2024] Open
Abstract
INTRODUCTION Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of medications for management of diabetes and obesity. The objective of this study is to characterize the epidemiology of GLP-1RA cases reported to US poison centers. METHODS We analyzed cases involving a GLP-1RA reported to the National Poison Data System during 2017-2022. RESULTS There were 5,713 single-substance exposure cases reported to US poison centers involving a GLP-1RA. Most cases were among females (71.3%) and attributable to therapeutic errors (79.9%). More than one-fifth (22.4%) of cases were evaluated in a healthcare facility, including 0.9% admitted to a critical care unit and 4.1% admitted to a non-critical care unit. Serious medical outcomes were described in 6.2% of cases, including one fatality. The rate of cases per one million US population increased from 1.16 in 2017 to 3.49 in 2021, followed by a rapid increase of 80.9% to 6.32 in 2022. Trends for rates of serious medical outcomes and admissions to a healthcare facility showed similar patterns with 129.9% and 95.8% increases, respectively, from 2021 to 2022. CONCLUSIONS Most GLP-1RA cases reported to US poison centers were associated with no or minimal effects and did not require referral for medical treatment; however, a notable minority of individuals experienced a serious medical outcome or healthcare facility admission. The rate of reported cases increased during the study period, including an 80.9% increase from 2021 to 2022. Opportunities exist to improve provider and patient awareness of the adverse effects of these medications.
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Affiliation(s)
- Christopher E Gaw
- Center for Injury Research and Policy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, 700 Children's Drive, 43205, Columbus, OH, USA
- Division of Emergency Medicine, Nationwide Children's Hospital, Columbus, OH, USA
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Hannah L Hays
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
- Section of Toxicology, Nationwide Children's Hospital, Columbus, OH, USA
- Central Ohio Poison Center, Nationwide Children's Hospital, Columbus, OH, USA
| | - Cydney A Kemp
- Center for Injury Research and Policy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, 700 Children's Drive, 43205, Columbus, OH, USA
- Campbell University School of Osteopathic Medicine, Lillington, NC, USA
| | - Sandhya Kistamgari
- Center for Injury Research and Policy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, 700 Children's Drive, 43205, Columbus, OH, USA
| | - Henry A Spiller
- Central Ohio Poison Center, Nationwide Children's Hospital, Columbus, OH, USA
| | - Natalie I Rine
- Central Ohio Poison Center, Nationwide Children's Hospital, Columbus, OH, USA
| | - Allison L Rhodes
- Division of General Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Motao Zhu
- Center for Injury Research and Policy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, 700 Children's Drive, 43205, Columbus, OH, USA
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
| | - Gary A Smith
- Center for Injury Research and Policy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, 700 Children's Drive, 43205, Columbus, OH, USA.
- Division of Emergency Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA.
- Child Injury Prevention Alliance, Columbus, OH, USA.
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Laeeq T, Ahmed M, Sattar H, Zeeshan MH, Ali MB. Role of SGLT2 Inhibitors, DPP-4 Inhibitors, and Metformin in Pancreatic Cancer Prevention. Cancers (Basel) 2024; 16:1325. [PMID: 38611003 PMCID: PMC11011099 DOI: 10.3390/cancers16071325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 03/08/2024] [Accepted: 03/27/2024] [Indexed: 04/14/2024] Open
Abstract
Pancreatic carcinoma is a highly aggressive tumor that usually presents when it has already metastasized. Therapeutic options for cure remain scarce and rely on combination chemotherapy with limited sustainability. Diabetes is considered an important risk factor for the development of pancreatic cancer due to the production of proinflammatory cytokines, which result in increased cell proliferation. More than half of patients diagnosed with pancreatic cancer eventually develop diabetes due to the destruction of insulin-producing cells. The interlinkage of both diseases might identify a possible preventative strategy for reducing the incidence of pancreatic carcinoma. This study reviewed the recent literature on the association between pancreatic cancer risk and SGLT2 inhibitors, GLP-1 RA, DPP-4 inhibitors, and biguanides. There are mixed data regarding the relationship between GLP-1 RA and DPP-4 inhibitors and pancreatic cancer, with some trials suggesting that they might increase the risk. In contrast, studies have mostly revealed that SGLT2 inhibitors have an antiproliferative effect on various tumors, such as liver, pancreatic, prostate, bowel, lung, and breast carcinoma, which might be due to their mechanism of blockage of reabsorption of glucose by cells, lowering the amount of available glucose for the growth of tumor cells. Metformin, the first-line agent for diabetes, has also been shown to be associated with decreasing pancreatic cancer risk and improving prognosis in those who already have the disease. Dedicated trials are needed to further delineate the association of antidiabetic drugs with the risk of pancreatic cancer in the general population, as previous studies have mostly focused on diabetic patients.
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Affiliation(s)
- Tooba Laeeq
- Internal Medicine, University of Nevada, 4505 S Maryland Pkwy, Las Vegas, NV 89154, USA
| | - Maheen Ahmed
- Internal Medicine, Dow University of Health Sciences, Mission Rd., New Labour Colony, Karachi 74200, Pakistan; (M.A.); (M.H.Z.)
| | - Hina Sattar
- Internal Medicine, Dow University of Health Sciences, Mission Rd., New Labour Colony, Karachi 74200, Pakistan; (M.A.); (M.H.Z.)
| | - Muhammad Hamayl Zeeshan
- Internal Medicine, Dow University of Health Sciences, Mission Rd., New Labour Colony, Karachi 74200, Pakistan; (M.A.); (M.H.Z.)
| | - Meher Binte Ali
- Internal Medicine, University of Maryland Medical Center, 827 Linden Ave., Baltimore, MD 21201, USA
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Pinto SFT, Santos HA, Sarmento BFCC. New insights into nanomedicines for oral delivery of glucagon-like peptide-1 analogs. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2024; 16:e1952. [PMID: 38500351 DOI: 10.1002/wnan.1952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Revised: 01/23/2024] [Accepted: 02/21/2024] [Indexed: 03/20/2024]
Abstract
Type 2 diabetes mellitus (T2DM) is a metabolic disorder that arises when the body cannot respond fully to insulin, leading to impaired glucose tolerance. Currently, the treatment embraces non-pharmacological actions (e.g., diet and exercise) co-associated with the administration of antidiabetic drugs. Metformin is the first-line treatment for T2DM; nevertheless, alternative therapeutic strategies involving glucagon-like peptide-1 (GLP-1) analogs have been explored for managing the disease. GLP-1 analogs trigger insulin secretion and suppress glucagon release in a glucose-dependent manner thereby, reducing the risk of hyperglycemia. Additionally, GLP-1 analogs have an extended plasma half-life compared to the endogenous peptide due to their high resistance to degradation by dipeptidyl peptidase-4. However, GLP-1 analogs are mainly administered via subcutaneous route, which can be inconvenient for the patients. Even considering an oral delivery approach, GLP-1 analogs are exposed to the harsh conditions of the gastrointestinal tract (GIT) and the intestinal barriers (mucus and epithelium). Hereupon, there is an unmet need to develop non-invasive oral transmucosal drug delivery strategies, such as the incorporation of GLP-1 analogs into nanoplatforms, to overcome the GIT barriers. Nanotechnology has the potential to shield antidiabetic peptides against the acidic pH and enzymatic activity of the stomach. In addition, the nanoparticles can be coated and/or surface-conjugated with mucodiffusive polymers and target intestinal ligands to improve their transport through the intestinal mucus and epithelium. This review focuses on the main hurdles associated with the oral administration of GLP-1 and GLP-1 analogs, and the nanosystems developed to improve the oral bioavailability of the antidiabetic peptides. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.
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Affiliation(s)
- Soraia Filipa Tavares Pinto
- Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal
- Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Porto, Portugal
| | - Hélder Almeida Santos
- Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
- W.J. Kolff Institute for Biomedical Engineering and Materials Science, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Bruno Filipe Carmelino Cardoso Sarmento
- Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal
- Instituto Universitário de Ciências da Saúde (IUCS-CESPU), Gandra, Portugal
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Blüher M, Rosenstock J, Hoefler J, Manuel R, Hennige AM. Dose-response effects on HbA 1c and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial. Diabetologia 2024; 67:470-482. [PMID: 38095657 PMCID: PMC10844353 DOI: 10.1007/s00125-023-06053-9] [Citation(s) in RCA: 33] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 08/17/2023] [Indexed: 01/25/2024]
Abstract
AIMS/HYPOTHESIS The aim of this study was to assess the dose-response effects of the subcutaneous glucagon receptor/glucagon-like peptide-1 receptor dual agonist survodutide (BI 456906) on HbA1c levels and bodyweight reduction. METHODS This Phase II, multicentre, randomised, double-blind, parallel-group, placebo-controlled study, conducted in clinical research centres, assessed survodutide in participants aged 18-75 years with type 2 diabetes, an HbA1c level of 53-86 mmol/mol (7.0-10.0%) and a BMI of 25-50 kg/m2 on a background of metformin therapy. Participants were randomised via interactive response technology to receive survodutide (up to 0.3, 0.9, 1.8 or 2.7 mg once weekly [qw; dose group (DG) 1-4, respectively] or 1.2 or 1.8 mg twice weekly [DG 5 and 6, respectively]), placebo or semaglutide (up to 1.0 mg qw). Participants and all those involved in the trial conduct/analysis were blinded; the semaglutide arm was open-label. The primary endpoint was absolute change from baseline in HbA1c after 16 weeks' treatment. The key secondary endpoint was relative change from baseline in bodyweight after 16 weeks' treatment. RESULTS A total of 413 participants were randomised (DG1, n=50; DG2, n=50; DG3, n=52; DG4, n=50; DG5, n=51; DG6, n=50; semaglutide, n=50; placebo, n=60). The full analysis set comprised 411 treated participants (DG6, n=49; placebo, n=59). Adjusted mean (95% CI) HbA1c decreased from baseline (mean ± SD 64.7±9.2 mmol/mol [8.07±0.84%] after 16 weeks' treatment: DG1 (n=41), -9.92 mmol/mol (-12.27, -7.56; -0.91% [-1.12, -0.69]); DG2 (n=46), -15.95 mmol/mol (-18.27, -13.63; -1.46% [-1.67, -1.25]); DG3 (n=36), -18.72 mmol/mol (-21.15, -16.29; -1.71% [-1.94, -1.49]); DG4 (n=33), -17.01 mmol/mol (-19.59, -14.43; -1.56% [-1.79, -1.32]); DG5 (n=44), -17.84 mmol/mol (-20.18, -15.51; -1.63% [-1.85, -1.42]); DG6 (n=36), -18.38 mmol/mol (-20.90, -15.87; -1.68% [-1.91, -1.45]). The mean reduction in HbA1c was similar with low-dose survodutide (DG2: -15.95 mmol/mol [-1.46%]; n=46) and semaglutide (-16.07 mmol/mol [-1.47%]; n=45). Mean (95% CI) bodyweight decreased dose-dependently up to -8.7% (-10.1, -7.3; DG6, n=37); survodutide ≥1.8 mg qw produced greater bodyweight reductions than semaglutide (-5.3% [-6.6, -4.1]; n=45). Adverse events (AEs) were reported for 77.8% of survodutide-treated participants (mainly gastrointestinal), 52.5% receiving placebo and 52.0% receiving semaglutide. CONCLUSIONS/INTERPRETATION Survodutide reduced HbA1c levels and bodyweight after 16 weeks' treatment in participants with type 2 diabetes. Dose-related gastrointestinal AEs could be mitigated with slower dose escalations. TRIAL REGISTRATION ClinicalTrials.gov NCT04153929 and EudraCT 2019-002390-60. FUNDING Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
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Affiliation(s)
- Matthias Blüher
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München, University of Leipzig and University Hospital Leipzig, Leipzig, Germany.
| | | | - Josef Hoefler
- Staburo GmbH, Munich, Germany, on behalf of Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany
| | - Raymond Manuel
- Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA
| | - Anita M Hennige
- Boehringer Ingelheim International GmbH, Biberach an der Riß, Germany.
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Ntentakis DP, Correa VSMC, Ntentaki AM, Delavogia E, Narimatsu T, Efstathiou NE, Vavvas DG. Effects of newer-generation anti-diabetics on diabetic retinopathy: a critical review. Graefes Arch Clin Exp Ophthalmol 2024; 262:717-752. [PMID: 37728754 DOI: 10.1007/s00417-023-06236-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 08/30/2023] [Accepted: 09/07/2023] [Indexed: 09/21/2023] Open
Abstract
Diabetic retinopathy (DR) is the leading etiology of blindness in the working population of the USA. Its long-term management relies on effective glycemic control. Seven anti-diabetic classes have been introduced for patients with type 2 diabetes (T2D) in the past two decades, with different glucose-lowering and cardiovascular benefits. Yet, their effects specifically on DR have not been studied in detail. A systematic review of the literature was conducted to investigate this topic, focusing on the available clinical data for T2D. Published studies were evaluated based on their level of statistical evidence, as long as they incorporated at least one endpoint or adverse event pertaining to retinal health. Fifty nine articles met our inclusion criteria and were grouped per anti-diabetic class as follows: alpha-glucosidase inhibitors (1), peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists (8), amylin analogs (1), glucagon-like peptide-1 (GLP-1) receptor agonists (28), dipeptidyl peptidase 4 (DPP-4) inhibitors (9), and sodium glucose co-transporter-2 (SGLT-2) inhibitors (9), plus one retrospective study and two meta-analyses evaluating more than one of the aforementioned anti-diabetic categories. We also reviewed publicly-announced results of trials for the recently-introduced class of twincretins. The available data indicates that most drugs in the newer anti-diabetic classes are neutral to DR progression; however, there are subclasses differences in specific drugs and T2D populations. In particular, there is evidence suggesting there may be worse diabetic macular edema with PPAR-gamma agonists, potential slight DR worsening with semaglutide (GLP-1 receptor agonist), and potential slight increase in the incidence of retinal vein occlusion in elderly and patients with advanced kidney disease receiving SGLT-2 inhibitors. All these warrant further investigation. Longer follow-up and systematic assessment of at least one DR-related endpoint are highly recommended for all future trials in the T2D field, to ultimately address this topic.
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Affiliation(s)
- Dimitrios P Ntentakis
- Ines and Fredrick Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Main Campus, 243 Charles Street, Harvard Medical School, Boston, MA, 02114, USA
| | - Victor San Martin Carvalho Correa
- Ines and Fredrick Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Main Campus, 243 Charles Street, Harvard Medical School, Boston, MA, 02114, USA
| | - Anastasia Maria Ntentaki
- Ines and Fredrick Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Main Campus, 243 Charles Street, Harvard Medical School, Boston, MA, 02114, USA
| | - Eleni Delavogia
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Toshio Narimatsu
- Ines and Fredrick Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Main Campus, 243 Charles Street, Harvard Medical School, Boston, MA, 02114, USA
| | - Nikolaos E Efstathiou
- Ines and Fredrick Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Main Campus, 243 Charles Street, Harvard Medical School, Boston, MA, 02114, USA
| | - Demetrios G Vavvas
- Ines and Fredrick Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Main Campus, 243 Charles Street, Harvard Medical School, Boston, MA, 02114, USA.
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Igweokpala S, Sule NO, Douros A, Yu OHY, Filion KB. Incretin-based drugs and the risk of diabetic retinopathy among individuals with type 2 diabetes: A systematic review and meta-analysis of observational studies. Diabetes Obes Metab 2024; 26:721-731. [PMID: 38031234 DOI: 10.1111/dom.15367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 10/20/2023] [Accepted: 10/30/2023] [Indexed: 12/01/2023]
Abstract
AIM The results from the SUSTAIN-6 trial generated some uncertainty regarding the association between incretin-based drugs [dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)] and the risk of diabetic retinopathy. Our objective was to synthesize the available evidence from observational studies regarding the use of incretin-based drugs and the risk of diabetic retinopathy among individuals with type 2 diabetes. MATERIALS AND METHODS We systemically searched Cochrane Library, Embase and Medline to identify observational studies of interest. Risk of bias was assessed using the ROBINS-I tool. Data from included studies were pooled using the DerSimonian and Laird random-effect model with the Hartung-Knapp extension. RESULTS We included 14 studies in the systematic review, with 10 examining DPP-4 inhibitors and seven examining GLP-1 RAs. Nine studies investigated incident diabetic retinopathy, six investigated diabetic retinopathy progression and two investigated both outcomes. Seven studies were at moderate risk of bias, four at serious risk of bias and three at critical risk of bias. Data pooled across studies showed no association between the use of DPP-4 inhibitors (risk ratio: 0.98, 95% confidence interval: 0.83, 1.17) or GLP-1 RAs (risk ratio: 0.87, 95% confidence interval: 0.56, 1.34) and the risk of diabetic retinopathy. CONCLUSION This study suggests that the use of incretin-based drugs is not associated with the risk of diabetic retinopathy among individuals with type 2 diabetes. However, these findings should be interpreted with caution considering the limited quality of some of the available evidence.
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Affiliation(s)
- Samuel Igweokpala
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
- Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
| | - Naheemot Olaoluwa Sule
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
- Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
| | - Antonios Douros
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
- Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
- Department of Medicine, McGill University, Montreal, Quebec, Canada
- Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Oriana H Y Yu
- Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
- Division of Endocrinology and Metabolism, Jewish General Hospital/McGill University, Montreal, Quebec, Canada
| | - Kristian B Filion
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
- Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
- Department of Medicine, McGill University, Montreal, Quebec, Canada
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Tan L, Wang Z, Okoth K, Toulis KA, Denniston AK, Singh BM, Crowe FL, Sainsbury C, Wang J, Nirantharakumar K. Associations of antidiabetic drugs with diabetic retinopathy in people with type 2 diabetes: an umbrella review and meta-analysis. Front Endocrinol (Lausanne) 2024; 14:1303238. [PMID: 38239984 PMCID: PMC10795175 DOI: 10.3389/fendo.2023.1303238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 12/06/2023] [Indexed: 01/22/2024] Open
Abstract
Background Diabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions regarding the administration of antidiabetic drugs do not sufficiently incorporate the risk of DR due to the inconclusive evidence from preceding meta-analyses. This umbrella review aimed to systematically evaluate the effects of antidiabetic drugs on DR in people with type 2 diabetes. Methods A systematic literature search was undertaken in Medline, Embase, and the Cochrane Library (from inception till 17th May 2022) without language restrictions to identify systematic reviews and meta-analyses of randomized controlled trials or longitudinal studies that examined the association between antidiabetic drugs and DR in people with type 2 diabetes. Two authors independently extracted data and assessed the quality of included studies using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist, and evidence assessment was performed using the GRADE (Grading of recommendations, Assessment, Development and Evaluation). Random-effects models were applied to calculate relative risk (RR) or odds ratios (OR) with 95% confidence intervals (CI). This study was registered with PROSPERO (CRD42022332052). Results With trial evidence from 11 systematic reviews and meta-analyses, we found that the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or dipeptidyl peptidase-4 inhibitors (DPP-4i) was not statistically associated with the risk of DR, compared to either placebo (RR: GLP-1 RA, 0.98, 0.89-1.08; SGLT-2i, 1.00, 95% CI 0.79-1.27; DPP-4i, 1.17, 0.99-1.39) or other antidiabetic drugs. Compared to other antidiabetic drugs, meglitinides (0.34, 0.01-8.25), SGLT-2i (0.73, 0.10-5.16), thiazolidinediones (0.92, 0.67-1.26), metformin (1.15, 0.81-1.63), sulphonylureas (1.24, 0.93-1.65), and acarbose (4.21, 0.44-40.43) were not statistically associated with the risk of DR. With evidence from longitudinal studies only, insulin was found to have a higher risk of DR than other antidiabetic drugs (OR: 2.47, 95% CI: 2.04-2.99). Conclusion Our results indicate that antidiabetic drugs are generally safe to prescribe regarding the risk of DR among people with type 2 diabetes. Further robust and large-scale trials investigating the effects of insulin, meglitinides, and acarbose on DR are warranted. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=332052, identifier CRD42022332052.
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Affiliation(s)
- Luyuan Tan
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Zhaonan Wang
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Kelvin Okoth
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Konstantinos A. Toulis
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Alastair K. Denniston
- Academic Unit of Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
- National Institute for Health and Care Research Birmingham Biomedical Research Centre, Birmingham, United Kingdom
| | - Baldev M. Singh
- Wolverhampton Diabetes Centre, New Cross Hospital, The Royal Wolverhampton National Health Service Trust, Wolverhampton, United Kingdom
- Research Institute in Healthcare Sciences, Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton, United Kingdom
| | - Francesca L. Crowe
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Christopher Sainsbury
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
| | - Jingya Wang
- Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
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Ehrhardt NM, Aroda VR, Galindo RJ, Peters AL, Shubrook JH. Use of Continuous Glucose Monitoring and Glucagon-Like Peptide 1 Receptor Agonist Therapy to Achieve Individualized Treatment Goals in Insulin-Treated People With Type 2 Diabetes: A Case Series and Expert Opinion. Clin Diabetes 2023; 42:341-350. [PMID: 38666194 PMCID: PMC11040021 DOI: 10.2337/cd23-0047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/28/2024]
Affiliation(s)
| | - Vanita R. Aroda
- Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
| | - Rodolfo J. Galindo
- Diabetes Research Institute, University of Miami Health System, Miami, FL
| | - Anne L. Peters
- Keck School of Medicine of the University of Southern California, Los Angeles, Los Angeles, CA
| | - Jay H. Shubrook
- College of Osteopathic Medicine, Touro University California, Vallejo, CA
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Goldney J, Sargeant JA, Davies MJ. Incretins and microvascular complications of diabetes: neuropathy, nephropathy, retinopathy and microangiopathy. Diabetologia 2023; 66:1832-1845. [PMID: 37597048 PMCID: PMC10474214 DOI: 10.1007/s00125-023-05988-3] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 07/17/2023] [Indexed: 08/21/2023]
Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1RAs, incretin mimetics) and dipeptidyl peptidase-4 inhibitors (DPP-4is, incretin enhancers) are glucose-lowering therapies with proven cardiovascular safety, but their effect on microvascular disease is not fully understood. Both therapies increase GLP-1 receptor agonism, which is associated with attenuation of numerous pathological processes that may lead to microvascular benefits, including decreased reactive oxygen species (ROS) production, decreased inflammation and improved vascular function. DPP-4is also increase stromal cell-derived factor-1 (SDF-1), which is associated with neovascularisation and tissue repair. Rodent studies demonstrate several benefits of these agents in the prevention or reversal of nephropathy, retinopathy and neuropathy, but evidence from human populations is less clear. For nephropathy risk in human clinical trials, meta-analyses demonstrate that GLP-1RAs reduce the risk of a composite renal outcome (doubling of serum creatinine, eGFR reduction of 30%, end-stage renal disease or renal death), whereas the benefits of DPP-4is appear to be limited to reductions in the risk of albuminuria. The relationship between GLP-1RAs and retinopathy is less clear. Many large trials and meta-analyses show no effect, but an observed increase in the risk of retinopathy complications with semaglutide therapy (a GLP-1RA) in the SUSTAIN-6 trial warrants caution, particularly in individuals with baseline retinopathy. Similarly, DPP-4is are associated with increased retinopathy risk in both trials and meta-analysis. The association between GLP-1RAs and peripheral neuropathy is unclear due to little trial evidence. For DPP-4is, one trial and several observational studies show a reduced risk of peripheral neuropathy, with others reporting no effect. Evidence in other less-established microvascular outcomes, such as microvascular angina, cerebral small vessel disease, skeletal muscle microvascular disease and autonomic neuropathies (e.g. cardiac autonomic neuropathy, gastroparesis, erectile dysfunction), is sparse. In conclusion, GLP-1RAs are protective against nephropathy, whereas DPP-4is are protective against albuminuria and potentially peripheral neuropathy. Caution is advised with DPP-4is and semaglutide, particularly for patients with background retinopathy, due to increased risk of retinopathy. Well-designed trials powered for microvascular outcomes are needed to clarify associations of incretin therapies and microvascular diseases.
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Affiliation(s)
- Jonathan Goldney
- Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, UK.
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and University of Leicester, Leicester, UK.
| | - Jack A Sargeant
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and University of Leicester, Leicester, UK
- Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Melanie J Davies
- Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, UK
- NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and University of Leicester, Leicester, UK
- Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester, UK
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Ochani RK, Shaikh A, Batra S, Pikale G, Surani S. Diabetes among Muslims during Ramadan: A narrative review. World J Clin Cases 2023; 11:6031-6039. [PMID: 37731557 PMCID: PMC10507567 DOI: 10.12998/wjcc.v11.i26.6031] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 07/21/2023] [Accepted: 08/09/2023] [Indexed: 09/08/2023] Open
Abstract
Fasting during the month of Ramadan is one of the five fundamental principles of Islam, and it is obligatory for healthy Muslim adults and adolescents. During the fasting month, Muslims usually have two meals a day, suhur (before dawn) and iftar (after dusk). However, diabetic patients may face difficulties when fasting, so it is important for medical staff to educate them on safe fasting practices. Prolonged strict fasting can increase the risk of hypoglycemia and diabetic ketoacidosis, but with proper knowledge, careful planning, and medication adjustment, diabetic Muslim patients can fast during Ramadan. For this review, a literature search was conducted using PubMed and Google Scholar until May 2023. Articles other than the English language were excluded. Current strategies for managing blood sugar levels during Ramadan include a combination of patient education on nutrition, regular monitoring of blood glucose, medications, and insulin therapy. Insulin therapy can be continued during fasting if properly titrated to the patients' needs, and finger prick blood sugar levels should be assessed regularly. If certain symptoms such as hypoglycemia, hyperglycemia, dehydration, or acute illness occur, or blood glucose levels become too high (> 300 mg/dL) or too low (< 70 mg/dL), the fast should be broken. New insulin formulations such as pegylated insulin and medications like tirzepatide, a dual agonist of gastric-inhibitory peptideand glucagonlike-peptide 1 receptors, have shown promise in managing blood sugar levels during Ramadan. Non-insulin-dependent medications like sodium-glucose-cotransporter-2 inhibitors, including the Food and Drug Administration-approved ertugliflozin, are also being used to provide additional cardiovascular benefits in patients with type 2 diabetes.
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Affiliation(s)
- Rohan Kumar Ochani
- Internal Medicine, SUNY Upstate Medical University Hospital, Syracuse, NY 13210, United States
| | - Asim Shaikh
- Medicine, Aga Khan University, Sindh, Karachi 74500, Pakistan
| | - Simran Batra
- Internal Medicine, Dow University of Health Sciences, Sindh, Karachi 74200, Pakistan
| | - Gauri Pikale
- Internal Medicine, Chicago Medical School at Rosalind Franklin University, Chicago, IL 60064, United States
| | - Salim Surani
- Medicine and Pharmacology, Texas A and M University, College Station, TX 77843, United States
- Medicine, Aga Khan University, Nairobi 00100, Kenya
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Nagendra L, Bg H, Sharma M, Dutta D. Semaglutide and cancer: A systematic review and meta-analysis. Diabetes Metab Syndr 2023; 17:102834. [PMID: 37531876 DOI: 10.1016/j.dsx.2023.102834] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 07/24/2023] [Accepted: 07/25/2023] [Indexed: 08/04/2023]
Abstract
BACKGROUND French national health care insurance system database has suggested 1-3 years use of glucagon like peptide-1 receptor agonists (GLP1RA) (exenatide, liraglutide and dulaglutide) may be linked with increased occurrence of thyroid cancer. Similar data on semaglutide is not-available. Hence, we undertook this systematic review to look at the safety of semaglutide focussing on different cancers. METHODS Databases were searched for randomized controlled trials (RCTs) and real-world studies involving patients receiving semaglutide in the intervention-arm. Primary outcome was to evaluate the occurrence of pancreatic and thyroid cancers. Secondary outcomes were to the evaluate occurrence of any other malignancies or severe adverse-events. RESULTS Data from 37 RCTs and 19 real-world studies having 16,839 patients in placebo-control group, 16,550 patients in active-control group and 13,330 patients in real-world studies were analysed. Compared to placebo, occurrence of pancreatic cancer [OR 0.25 (95%CI: 0.03-2.24); P = 0.21], thyroid cancer [OR 2.04 (95%CI: 0.33-12.61); P = 0.44; I2 = 0%] and all neoplasms (benign, malignant and otherwise unspecified) [OR 0.95 (95%CI:0.62-1.45); P = 0.82; I2 = 0%] was similar in the semaglutide group. Compared to active controls, occurrence of pancreatic cancer [OR 0.40 (95%CI:0.09-1.87); P = 0.26; I2 = 0%], thyroid cancer [OR 1.19 (95%CI:0.15-9.66); P = 0.87; I2 = 0%] and all neoplasms (benign, malignant and otherwise unspecified) [OR 0.91 (95% CI: 0.44-1.89); P = 0.79; I2 = 0%] were similar in the semaglutide group. Real-world data analysis revealed single case each of pancreatic cancer and B-cell lymphoma. CONCLUSION Semaglutide use in RCTs and real-world studies was not associated with an increased risk of any types of cancer, and this conclusion is supported by a high grade of evidence.
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Affiliation(s)
- Lakshmi Nagendra
- Department of Endocrinology, JSS Academy of Higher Education and Research, Mysore, India.
| | - Harish Bg
- Department of Anaesthesiology, JSS Academy of Higher Education and Research, Mysore, India.
| | - Meha Sharma
- Department of Rheumatology, Center for Endocrinology Diabetes Arthritis & Rheumatism (CEDAR) Superspeciality Healthcare, Dwarka, New Delhi, India.
| | - Deep Dutta
- Department of Endocrinology, Center for Endocrinology Diabetes Arthritis & Rheumatism (CEDAR) Superspeciality Healthcare, Dwarka, New Delhi, India.
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Rossing P, Bain SC, Bosch-Traberg H, Sokareva E, Heerspink HJL, Rasmussen S, Mellbin LG. Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis. Cardiovasc Diabetol 2023; 22:220. [PMID: 37620807 PMCID: PMC10463803 DOI: 10.1186/s12933-023-01949-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 08/02/2023] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects. This post hoc analysis investigated the association between major adverse cardiovascular events (MACE) and baseline kidney parameters and whether the effect of semaglutide on MACE risk was impacted by baseline kidney parameters in people with T2D at high cardiovascular risk. METHODS Participants from the SUSTAIN 6 and PIONEER 6 trials, receiving semaglutide or placebo, were categorised according to baseline kidney function (estimated glomerular filtration rate [eGFR] < 45 and ≥ 45-<60 versus ≥ 60 mL/min/1.73 m2) or damage (urine albumin:creatinine ratio [UACR] ≥ 30-≤300 and > 300 versus < 30 mg/g). Relative risk of first MACE by baseline kidney parameters was evaluated using a Cox proportional hazards model. The same model, adjusted with inverse probability weighting, and a quadratic spline regression were applied to evaluate the effect of semaglutide on risk and event rate of first MACE across subgroups. The semaglutide effects on glycated haemoglobin (HbA1c), body weight (BW) and serious adverse events (SAEs) across subgroups were also evaluated. RESULTS Independently of treatment, participants with reduced kidney function (eGFR ≥ 45-<60 and < 45 mL/min/1.73 m2: hazard ratio [95% confidence interval]; 1.36 [1.04;1.76] and 1.52 [1.15;1.99]) and increased albuminuria (UACR ≥ 30-≤300 and > 300 mg/g: 1.53 [1.14;2.04] and 2.52 [1.84;3.42]) had an increased MACE risk versus those without. Semaglutide consistently reduced MACE risk versus placebo across all eGFR and UACR subgroups (interaction p value [pINT] > 0.05). Semaglutide reduced HbA1c regardless of baseline eGFR and UACR (pINT>0.05); reductions in BW were affected by baseline eGFR (pINT<0.001) but not UACR (pINT>0.05). More participants in the lower eGFR or higher UACR subgroups experienced SAEs versus participants in reference groups; the number of SAEs was similar between semaglutide and placebo arms in each subgroup. CONCLUSIONS MACE risk was greater for participants with kidney impairment or damage than for those without. Semaglutide consistently reduced MACE risk across eGFR and UACR subgroups, indicating that semaglutide provides cardiovascular benefits in people with T2D and at high cardiovascular risk across a broad spectrum of kidney function and damage. TRIAL REGISTRATIONS NCT01720446; NCT02692716.
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37
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Patoulias D, Popovic DS, Stoian AP, Janez A, Sahebkar A, Rizzo M. Effect of semaglutide versus other glucagon-like peptide-1 receptor agonists on cardio-metabolic risk factors in patients with type 2 diabetes: A systematic review and meta-analysis of head-to-head, phase 3, randomized controlled trials. J Diabetes Complications 2023; 37:108529. [PMID: 37301063 DOI: 10.1016/j.jdiacomp.2023.108529] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 05/26/2023] [Accepted: 06/04/2023] [Indexed: 06/12/2023]
Abstract
INTRODUCTION Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a cornerstone treatment for type 2 diabetes mellitus (T2DM). The aim of the present meta-analysis was to assess whether semaglutide exerts greater effects on glycemia and other cardio-metabolic risk factors compared to other GLP-1RAs. METHODS PubMed and Cochrane Library databases, along with grey literature sources, were searched form inception to 8th February 2023, in order to retrieve head-to-head, phase 3 randomized controlled trials (RCTs) assessing the effect of semaglutide versus other GLP-1RAs on glycemia and other cardio-metabolic risk factors in T2DM. RESULTS We finally pooled data from 5 RCTs in a total of 3760 randomized participants. Semaglutide compared to other GLP-1RAs provided a significantly greater reduction in HbA1c levels by 0.44 %, in fasting plasma glucose by 0.48 mmol/L, in body weight by 2.53 kg and in body mass index by 0.91 kg/m2. Subjects receiving semaglutide experienced significantly greater odds for achieving target and optimal HbA1c, along with significantly greater odds for weight loss >5 % and 10 %. However, subjects randomized to semaglutide also experienced significantly greater odds for gastrointestinal adverse events and treatment discontinuation. CONCLUSION Semaglutide is more effective than rest GLP-1RAs, in terms of improvement in glycemia and other cardio-metabolic risk factors, among individuals with T2DM.
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Affiliation(s)
- Dimitrios Patoulias
- Outpatient Department of Cardiometabolic Medicine, Second Department of Cardiology, Aristotle University of Thessaloniki, General Hospital "Hippokration", Thessaloniki, Greece.
| | - Djordje S Popovic
- Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Center of Vojvodina, Medical Faculty, University of Novi Sad, Novi Sad, Serbia
| | - Anca Pantea Stoian
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Andrej Janez
- Department of Endocrinology, Diabetes and Metabolic Diseases, Medical Center, University of Ljubljana Medical Faculty, Ljubljana, Slovenia
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Manfredi Rizzo
- School of Medicine, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, Italy
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Sherwin M, Hamburger J, Katz D, DeMaria S. Influence of semaglutide use on the presence of residual gastric solids on gastric ultrasound: a prospective observational study in volunteers without obesity recently started on semaglutide. Can J Anaesth 2023; 70:1300-1306. [PMID: 37466909 DOI: 10.1007/s12630-023-02549-5] [Citation(s) in RCA: 58] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 05/30/2023] [Accepted: 06/22/2023] [Indexed: 07/20/2023] Open
Abstract
PURPOSE Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have become increasingly popular as both diabetic and weight loss therapies. One effect of this class of medication is delayed gastric emptying, which may impact the risk of aspiration during anesthesia delivery. METHODS In this prospective study, we used gastric ultrasound to evaluate the presence of solid gastric contents in both supine and lateral positions after an eight-hour fast in those taking GLP-1RA compared with controls. Participants underwent a second ultrasound evaluation two hours later after drinking 12 fluid ounces of water (approximately 350 mL). RESULTS Twenty adults voluntarily enrolled, giving a total of ten participants in each group. In the supine position, 70% of semaglutide participants and 10% of control participants had solids present on gastric ultrasound (risk ratio [RR], 3.50; 95% confidence interval [CI], 1.26 to 9.65; P = 0.02.) In the lateral position, 90% of semaglutide participants and 20% of control participants had solids identified on gastric ultrasound (RR, 7.36; 95% CI, 1.13 to 47.7; P = 0.005). Two hours after drinking clear liquids, the two groups did not differ in the lateral position, but in the supine position, 90% of control group participants were rated as empty compared with only 30% of semaglutide group participants (P = 0.02). CONCLUSIONS This study provides preliminary evidence that GLP-1RAs may affect gastric emptying and residual gastric contents following an overnight fast and two hours after clear liquids, which may have implications for aspiration risk during anesthetic care.
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Affiliation(s)
- Marc Sherwin
- Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L., Levy Place, Box 1010, New York, NY, 10029, USA
| | - Joshua Hamburger
- Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L., Levy Place, Box 1010, New York, NY, 10029, USA
| | - Daniel Katz
- Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L., Levy Place, Box 1010, New York, NY, 10029, USA
| | - Samuel DeMaria
- Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L., Levy Place, Box 1010, New York, NY, 10029, USA.
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Chen H, Li XZ, Chen JQ, Ren TS, Zhang YS, Wang YN, Zhao QC. Comparative efficacy and safety of glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes: A network meta-analysis. Medicine (Baltimore) 2023; 102:e34122. [PMID: 37417602 PMCID: PMC10328610 DOI: 10.1097/md.0000000000034122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 06/06/2023] [Accepted: 06/07/2023] [Indexed: 07/08/2023] Open
Abstract
INTRODUCTION This study aimed to evaluate the clinical efficacy and safety of 4 weekly formulations of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on glycemic control, including glycemic control, by using a network meta-analysis (NMA). METHODS PubMed, EMBASE, and Cochrane Library Central Register of Controlled Trials were searched from inception until June 10, 2022. Randomized clinical trials (RCTs) enrolling participants with diabetes mellitus type 2 and a follow-up of at least 12 weeks were included, for which 4 eligible GLP-1RAs Exenatide, Dulaglutide, Semaglutide, Loxenatide were compared with either each other or placebo. The primary outcome is the change of hemoglobin A1c level. Secondary outcomes including additional glycemic control indicators and adverse events (AE). Frequentist random-effect NMA were conducted for effect comparison. This meta-analysis was registered on PROSPERO, CRD42022342241. RESULTS The NMA synthesized evidence from 12 studies covering 6213 patients and 10 GLP-1RA regimens. A pairwise comparison of glycosylated hemoglobin type A1C (HbA1c) lowering effects showed that once-weekly GLP-1 receptor agonists were significantly better than placebo, and their glucose-lowering intensity was Semaglutide 2.0mg, Semaglutide 1.0mg, Dulaglutide 4.5mg, and Semaglutide 0.5mg, Dulaglutide 3.0mg, PEX168 200ug, Dulaglutide 1.5mg, PEX168 100ug and Dulaglutide 0.75mg. The GLP-1RA regimen has a comparable safety profile for hypoglycemia. And with the exception of PEX168, all other long-acting GLP-1RA drugs had lower rates of diarrhea, nausea and vomiting than placebo. CONCLUSION Regimens of GLP-1RAs had differential glycemic control. The efficacy and safety of Semaglutide 2.0mg in comprehensively lowering blood sugar showed the best performance.
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Affiliation(s)
- Han Chen
- Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, People’s Republic of China
| | - Xin-Zhu Li
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
| | - Jia-Qing Chen
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
| | - Tian-Shu Ren
- Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, People’s Republic of China
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
| | - Ying-Shi Zhang
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
| | - Yi-Nuo Wang
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
| | - Qing-Chun Zhao
- Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, People’s Republic of China
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China
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Mourougavelou V, Chowdhury TA. Management of hyperglycaemia in people with obesity. Clin Med (Lond) 2023; 23:364-371. [PMID: 38614651 PMCID: PMC10541039 DOI: 10.7861/clinmed.2023-0135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2023]
Abstract
Diabetes and obesity are closely interlinked. Obesity is a major risk factor for the development of type 2 diabetes mellitus and appears to be an important risk factor for diabetic micro- and macrovascular complications. Management of hyperglycaemia in people with diabetes is important to reduce diabetes-related complications. Previously, there was a significant tension between management of hyperglycaemia and mitigating weight gain. Older drugs, such as sulfonylureas, glitazones, and insulin, although effective antihyperglycaemic agents, tend to induce weight gain. There is now an increasing recognition in people with obesity and diabetes that the focus should be on aiding weight loss, initially with improvements in diet and physical activity, possibly with the use of low-calorie diet programmes. Subsequent addition of metformin and newer agents, such as sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 analogues, will aid glucose control and weight reduction, and offer cardiovascular and renal protection. These drugs are now much higher in the therapeutic pathway in many national and international guidelines. Bariatric surgery may also be an effective way to manage hyperglycaemia or induce remission in individuals with both obesity and diabetes.
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Liarakos AL, Koliaki C. Novel Dual Incretin Receptor Agonists in the Spectrum of Metabolic Diseases with a Focus on Tirzepatide: Real Game-Changers or Great Expectations? A Narrative Review. Biomedicines 2023; 11:1875. [PMID: 37509514 PMCID: PMC10377278 DOI: 10.3390/biomedicines11071875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 06/24/2023] [Accepted: 06/29/2023] [Indexed: 07/30/2023] Open
Abstract
The prevalence of metabolic diseases including type 2 diabetes (T2D), obesity and non-alcoholic fatty liver disease (NAFLD) increases globally. This highlights an unmet need for identifying optimal therapies for the management of these conditions. Tirzepatide is a novel dual incretin receptor agonist (twincretin) that activates both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. The aim of this narrative review was to examine the impact of novel twincretins, focusing on tirzepatide, on the management of a wide spectrum of metabolic diseases. Data from preclinical and clinical trials have shown that twincretins significantly reduce blood glucose levels in T2D, and tirzepatide is the first agent of this class that has been approved for the management of T2D. Additionally, the beneficial impact of tirzepatide on weight reduction has been corroborated in several studies, showing that this agent can achieve substantial and sustained weight loss in obese patients with or without T2D. Data also suggest that tirzepatide could be a promising drug for hepatic steatosis reduction in individuals with NAFLD. The remarkable effects of tirzepatide on glycaemic control, weight loss and liver-related outcomes have posed new research questions that are likely to lead to further advancements in the treatment of T2D, obesity and related metabolic disorders.
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Affiliation(s)
| | - Chrysi Koliaki
- First Propaedeutic Department of Internal Medicine and Diabetes Center, Laiko General Hospital, Medical Faculty, National Kapodistrian University of Athens, 11527 Athens, Greece
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Kalinkova M, Kadiyska T, Handjieva-Darlenska T. Pharmacogenetics of Glucagon-like-peptide-1 receptor in diabetes management. PHARMACIA 2023; 70:383-390. [DOI: 10.3897/pharmacia.70.e104481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder, primarily characterized by a decrease in insulin secretion and typically accompanied by insulin resistance. When untreated, T2DM is leading to an inevitable long-term complication. However, the novel treatment of T2DM like for example Glucagon-like Peptide-1 receptor agonists (GLP-1 RAs) give new perspectives for the patients to achieve a better glycemic control and additional metabolic improvements. Pharmacogenetics is a field in pharmacotherapy, which investigates the individual response to the medical treatment, according to polymorphic variations in the receptors of the drugs. This review aims to summarize current scientific evidence on the pharmacogenetics of the GLP-1 RA /liraglutide/ and the possible implementation in the treatment of T2D.
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Liarakos AL, Tentolouris A, Kokkinos A, Eleftheriadou I, Tentolouris N. Impact of Glucagon-like peptide 1 receptor agonists on peripheral arterial disease in people with diabetes mellitus: A narrative review. J Diabetes Complications 2023; 37:108390. [PMID: 36610322 DOI: 10.1016/j.jdiacomp.2022.108390] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 12/12/2022] [Accepted: 12/25/2022] [Indexed: 12/31/2022]
Abstract
Peripheral arterial disease (PAD) is a common macrovascular complication of diabetes mellitus (DM). Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) are among the latest class of antidiabetic medications that stimulate insulin synthesis and secretion and have been used for the management of type 2 DM. Apart from the effect on glycaemic control, GLP-1RAs also have a robust impact on weight reduction and have shown favorable effects on cardiovascular morbidity and mortality in cardiovascular outcome trials (CVOTs). The aim of this review was to examine the impact of GLP1-RAs on PAD among people with DM based on CVOTs, randomized controlled trials, observational studies as well as systematic reviews and meta-analyses. Data from retrospective studies and meta-analyses have shown superiority of these agents in comparison with other antidiabetic medications such as sodium-glucose cotransporter type 2 inhibitors and dipeptidyl peptidase-4 inhibitors in terms of PAD-related events. Nevertheless, data from CVOTs regarding the impact of GLP-1RAs on PAD are scarce and hence, safe conclusions regarding their effects cannot be drawn. Further prospective studies are needed to examine the impact of GLP-1RAs on PAD-related incidents including major adverse limb events, lower limb amputations and revascularization procedures.
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Affiliation(s)
| | - Anastasios Tentolouris
- First Department of Propaedeutic Internal Medicine and Diabetes Center, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Alexandros Kokkinos
- First Department of Propaedeutic Internal Medicine and Diabetes Center, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Ioanna Eleftheriadou
- First Department of Propaedeutic Internal Medicine and Diabetes Center, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Nikolaos Tentolouris
- First Department of Propaedeutic Internal Medicine and Diabetes Center, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
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Effect of glucagon-like peptide-1 receptor agonists on glycemic control, and weight reduction in adults: A multivariate meta-analysis. PLoS One 2023; 18:e0278685. [PMID: 36696429 PMCID: PMC9876280 DOI: 10.1371/journal.pone.0278685] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 11/22/2022] [Indexed: 01/26/2023] Open
Abstract
AIMS To explore the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) on glycemic control and weight reduction in adults. METHODS Databases were searched from August 2021 to March 2022. Data were analyzed using mean difference (MD) values with 95% confidence intervals (CIs). Both random-and fixed-effect models were employed. Heterogeneity was explored using pre-specified subgroup analyses and meta-regression. Structural equation modeling fitting was used for the multivariate meta-analysis. RESULTS A total of 31 double-blind randomized controlled trials with 22,948 participants were included in the meta-analysis. The MD and 95% CI of the pooled GLP1-RA-induced change in the glycated hemoglobin level was -0.78% (-0.97%, -0.60%) in the random-effects model and -0.45% (-0.47%, -0.44%) in the fixed-effect model, with a high heterogeneity (I2 = 97%). The pooled body weight reduction was -4.05 kg (-5.02 kg, -3.09 kg) in the random-effects model and -2.04 kg (-2.16 kg, -1.92 kg) in the fixed-effect model (I2 = 98%). The standardized pooled correlation coefficient between HbA1c levels and body weight was -0.42. A negative correlation between glycemic control and weight reduction was obtained. CONCLUSION Long-acting GLP-1 RAs significantly reduced the glycated hemoglobin level and body weight in adults.
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Alem MM. Effect of low dose allopurinol on glycemic control and glycemic variability in patients with type 2 diabetes mellitus: A cross-sectional study. Heliyon 2022; 8:e11549. [PMID: 36406683 PMCID: PMC9667255 DOI: 10.1016/j.heliyon.2022.e11549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 04/06/2022] [Accepted: 11/03/2022] [Indexed: 11/11/2022] Open
Abstract
Background Type 2 diabetes mellitus (DM), gout, and asymptomatic hyperuricemia are inter-connected pathologies. Glycemic control (GC), involving a range of treatments is central to the management of DM, whereas allopurinol continues to be the most widely recommended urate lowering agent. Allopurinol has been shown to possess anti-oxidant properties: this study explores the potential effect of allopurinol on glucose homeostasis. Methods This is an observational study with a cross-sectional design performed on patients with type 2 diabetes mellitus (DM), recruited from centers in Saudi Arabia. Patients were divided into two groups; allopurinol users; (for gout or asymptomatic hyperuricemia) and a matching disease control group. Patient demographics, co-morbid conditions, biochemical tests, and pharmacological treatments were extracted from electronic records to investigate the effect of allopurinol therapy on Glycemic control (GC), as assessed by glycated haemoglobin (HbA1c as primary endpoint), and on parameters of glycaemic variability (GV) (secondary endpoints). Results A total of 194 patients with type 2 DM were recruited (97 in both groups). The two groups were matched for age, sex, and duration of DM: mean age: 59.4 years, 73% males, and 122 months in the allopurinol group vs 59.6 years, 73% males, and 113 months in the control group. Antidiabetic medications were matched between the two groups. In the allopurinol group, it was prescribed with a daily dose of 100 mg, for 77% of the patients, with median duration of 39.5 months. HbA1c values were; 6.90% (6.20, 7.80) in the allopurinol group vs 7.30% (6.60, 8.40) in the control group (P = 0.010). Parameters of GV were calculated from 3 consecutive fasting blood sugar (FBS) readings: variability independent of the mean (VIM) was 0.140 in the allopurinol group vs 0.987 in the control group (P < 0.001). Conclusion Concomitant low-dose allopurinol therapy in patients with type 2 DM was associated with modest but significant improvements in GC and GV.
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Shobako N, Goto C, Nakagawa T, Yamato T, Kondo S, Nakamura F, Nakazeko T, Hirano Y, Honda K. Hypotensive and HbA1c reducing effect of novel dietary intervention program “COMB meal program”: Two randomized clinical trials. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
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Shu Y, He X, Wu P, Liu Y, Ding Y, Zhang Q. Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system. Front Public Health 2022; 10:996179. [PMID: 36339230 PMCID: PMC9631444 DOI: 10.3389/fpubh.2022.996179] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Accepted: 09/30/2022] [Indexed: 01/26/2023] Open
Abstract
Background Semaglutide was approved for treatment of type 2 diabetes mellitus (T2DM) and chronic weight management in obesity or overweight adults. However, real-world data regarding its long-term gastrointestinal safety and tolerability in large sample population are incomplete. We evaluated semaglutide-associated gastrointestinal safety signals by data mining of the FDA pharmacovigilance database. Methods Reporting odds ratio (ROR) was employed to quantify the signals of semaglutide-related gastrointestinal adverse events (AEs) from 2018 to 2022. Serious and non-serious cases were compared by Mann-Whitney U test or Chi-squared (χ2) test, and signals were prioritized using a rating scale. Results We identified 5,442 cases of semaglutide-associated gastrointestinal AEs, with 45 signals detected, ranging from a ROR025 of 1.01 (hypoaesthesia oral) to 42.03 (eructation), among which 17 AEs were identified as new and unexpected signals. Patient age (p < 0.001) and body weight (p = 0.006) rather than sex (p = 0.251) might be associated with an increased risk of gastrointestinal AEs severity. Notably, the association between semaglutide and gastrointestinal disorders remained when stratified by age, body weight, sex and reporter type. One strong, 22 moderate and 22 weak clinical priority signals were defined. The median time-to-onset (TTO) for strong clinical priority signal was 23 days, while for moderate and weak, they were 6 and 7 days, respectively. All of the disproportionality signals had early failure type features, suggesting that the risk of gastrointestinal AEs occurrence gradually decreased over time. Conclusion Our study provided a deeper and broader understanding of semaglutide's gastrointestinal safety profiles, which would help healthcare professionals to mitigate the risk of gastrointestinal AEs in clinical practice.
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Affiliation(s)
- Yamin Shu
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xucheng He
- Department of Pharmacy, Pengzhou Second People's Hospital, Pengzhou, China
| | - Pan Wu
- Department of Pharmacy, Chengfei Hospital, Chengdu, China
| | - Yanxin Liu
- Department of Pharmacy, Pengzhou People's Hospital, Pengzhou, China
| | - Yufeng Ding
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qilin Zhang
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China,*Correspondence: Qilin Zhang
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Alhindi Y, Avery A. The efficacy and safety of oral semaglutide for glycaemic management in adults with type 2 diabetes compared to subcutaneous semaglutide, placebo, and other GLP-1 RA comparators: A systematic review and network meta-analysis. Contemp Clin Trials Commun 2022; 28:100944. [PMID: 35812819 PMCID: PMC9260263 DOI: 10.1016/j.conctc.2022.100944] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 05/26/2022] [Accepted: 06/07/2022] [Indexed: 01/16/2023] Open
Abstract
Aim Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) indicated for glycaemic management in adults with type 2 diabetes (T2D). Oral semaglutide administration can help decrease glycated haemoglobin (HbA1c) and body weight in people with uncontrolled T2D. We evaluated the efficacy and safety of oral semaglutide compared to that of subcutaneous semaglutide, placebo, and other GLP-1 RAs in the treatment of T2D. Methods Randomised controlled trials of subcutaneous and oral semaglutide for glycaemic control in adults with T2D were selected from the Cochrane Central Register of Controlled Trials and PubMed. Mean differences (MDs) and risk ratios with 95% confidence intervals (CIs) were used to synthesise the results, and oral and subcutaneous semaglutide formulations were indirectly compared using mixed treatment comparisons. Results Twelve studies were included in this review (6840 participants). Oral semaglutide (14.0 mg) significantly reduced HbA1c (MD, −1.30% [95%CI: -1.44, −1.16], P < 0.05) and body weight (MD, −3.17 kg [95%CI: -3.89, −2.45], P < 0.05) compared to placebo (MD, HbA1c: -0.32% [95%CI: -0.49, −0.15], P < 0.05; MD body weight: -2.56 kg [95%CI: -3.41, −1.71], P < 0.05), liraglutide (1.2 mg), exenatide ER (2.0 mg), and dulaglutide (1.5 mg). Oral semaglutide was slightly less effective than subcutaneous semaglutide in reducing HbA1c levels (MD: -0.26% [95%CI: -0.44, −0.07], P < 0.05) and body weight (MD: -1.08 kg [95%CI: -2.04, −0.12], P < 0.05). Oral semaglutide increased the incidence of adverse events (nausea, diarrhoea, dyspepsia, and vomiting) compared to placebo, liraglutide (1.2 mg), exenatide (ER, 2.0 mg), and dulaglutide 1.5 mg but not compared to subcutaneous semaglutide. Conclusion Oral semaglutide was non-inferior to subcutaneous semaglutide and superior to placebo and another GLP-1 RA in reducing HbA1c and body weight. It was superior to subcutaneous semaglutide and inferior to other GLP-1 RA comparators and placebo in terms of the incidence of adverse events. Thus, oral semaglutide provides a convenient administration route for patients who prefer oral treatments over injectable therapies.
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Affiliation(s)
- Yousef Alhindi
- Division of Food, Nutrition & Dietetics, University of Nottingham, UK
- Division of Applied Medical Sciences, University of Hail, Saudi Arabia
- Corresponding author. Nottinghamshire, Nottingham, NG1 1AS, UK.
| | - Amanda Avery
- Division of Food, Nutrition & Dietetics, University of Nottingham, UK
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Chavda VP, Ajabiya J, Teli D, Bojarska J, Apostolopoulos V. Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review. Molecules 2022; 27:4315. [PMID: 35807558 PMCID: PMC9268041 DOI: 10.3390/molecules27134315] [Citation(s) in RCA: 81] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 06/28/2022] [Accepted: 07/04/2022] [Indexed: 02/07/2023] Open
Abstract
The prevalence of obesity and diabetes is an increasing global problem, especially in developed countries, and is referred to as the twin epidemics. As such, advanced treatment approaches are needed. Tirzepatide, known as a 'twincretin', is a 'first-in-class' and the only dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptor agonist, that can significantly reduce glycemic levels and improve insulin sensitivity, as well as reducing body weight by more than 20% and improving lipid metabolism. This novel anti-diabetic drug is a synthetic peptide analog of the human GIP hormone with a C20 fatty-diacid portion attached which, via acylation technology, can bind to albumin in order to provide a dose of the drug, by means of subcutaneous injection, once a week, which is appropriate to its a half-life of about five days. Tirzepatide, developed by Eli Lilly, was approved, under the brand name Mounjaro, by the United States Food and Drug Administration in May 2022. This started the 'twincretin' era of enormously important and appealing dual therapeutic options for diabetes and obesity, as well as advanced management of closely related cardiometabolic settings, which constitute the leading cause of morbidity, disability, and mortality worldwide. Herein, we present the key characteristics of tirzepatide in terms of synthesis, structure, and activity, bearing in mind its advantages and shortcomings. Furthermore, we briefly trace the evolution of this kind of medical agent and discuss the development of clinical studies.
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Affiliation(s)
- Vivek P. Chavda
- Department of Pharmaceutics and Pharmaceutical Technology, LM College of Pharmacy, Ahmedabad 380009, India
| | - Jinal Ajabiya
- Department of Pharmaceutics Analysis and Quality Assurance, LM College of Pharmacy, Ahmedabad 380009, India;
| | - Divya Teli
- Department of Pharmaceutical Chemistry, LM College of Pharmacy, Ahmedabad 380009, India;
| | - Joanna Bojarska
- Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, 116 Żeromskiego Street, 90-924 Lodz, Poland
| | - Vasso Apostolopoulos
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia
- Australian Institute for Musculoskeletal Science (AIMSS), Immunology Program, Melbourne, VIC 3030, Australia
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Semaglutide is precipitating a revolution in obesity care. TRANSLATIONAL METABOLIC SYNDROME RESEARCH 2022. [DOI: 10.1016/j.tmsr.2022.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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