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Teo V, Hodgkinson A, Weinman J, Chamley M, Yap KZ. A validation study of the Intentional Nonadherence Scale among people with type 2 diabetes in the United Kingdom. Diabet Med 2025; 42:e70040. [PMID: 40186412 PMCID: PMC12080987 DOI: 10.1111/dme.70040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Revised: 03/25/2025] [Accepted: 03/26/2025] [Indexed: 04/07/2025]
Abstract
AIM To examine the psychometric properties of the Intentional Nonadherence Scale (INAS) among people with type 2 diabetes mellitus (PwT2D) in the United Kingdom. METHODS This validation study recruited 260 PwT2D at diabetes intermediate care team clinics in London. Thirty of them participated in the test-retest reliability analysis in 2-4 weeks, while 124 were followed up in 3-6 months for the predictive validity analysis. The psychometric evaluation also comprised internal reliability, structural validity and construct validity that assessed the relationship between the INAS and other established measures, such as the Medication Adherence Report Scale-5 (MARS-5), Beliefs about Medicine Questionnaire (BMQ)-specific, Brief Illness Perception Questionnaire (BIPQ), Patient Health Questionnaire-2 (PHQ-2) and glycated haemoglobin (HbA1c). RESULTS Exploratory factor analysis revealed four factors, namely 'Resisting illness', 'Resisting medication', 'Testing treatment' and 'Sensitivity to medication'. All INAS factors demonstrated high internal reliability (Cronbach's alpha = 0.92-0.96). Their test-retest reliability varied between <0.001 and 0.92. Construct validity was demonstrated by its relationship with other measures, including its negative correlations with medication adherence and positive correlations with medication concerns. Significant correlations were also found with HbA1c, as well as with PwT2D's perceptions of diabetes consequences, treatment control, identity and emotional responses to diabetes. 'Testing Treatment' showed a trend towards statistical significance with adherence in 3-6 months (coefficient = -0.34, p = 0.09). CONCLUSIONS The INAS performed well on a number of psychometric properties in this study. It may be a helpful tool for clinicians in identifying specific drivers of intentional nonadherence among PwT2D.
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Affiliation(s)
- Vivien Teo
- Institute of Pharmaceutical Sciences, King's College LondonLondonUK
- Department of PharmacyNational University of SingaporeSingaporeSingapore
| | - Anna Hodgkinson
- Lambeth Diabetes Intermediate Care TeamGuy's and St Thomas' NHS Foundation TrustLondonUK
| | - John Weinman
- Institute of Pharmaceutical Sciences, King's College LondonLondonUK
| | - Mark Chamley
- Lambeth Diabetes Intermediate Care TeamGuy's and St Thomas' NHS Foundation TrustLondonUK
| | - Kai Zhen Yap
- Department of PharmacyNational University of SingaporeSingaporeSingapore
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Saran A, Raisinghani R, Paliwal S, Sharma S. GLP-1R agonists: recent advances, current gaps, and future challenges. Mol Divers 2025:10.1007/s11030-025-11195-6. [PMID: 40301134 DOI: 10.1007/s11030-025-11195-6] [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: 02/06/2025] [Accepted: 04/11/2025] [Indexed: 05/01/2025]
Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) emerged as a promising class of drugs and have been shown to be effective as a key regulator in managing glucose metabolism-associated diseases such as type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), cardiovascular effects, nephrological complications, diabetes, non-alcoholic fatty liver (NAFLD), as well as to control obesity. A few drugs included in GLP-1RA class are liraglutide, exenatide, and semaglutide. Most recent drug that is available in both oral and subcutaneous forms is semaglutide. Available, withdrawn, and investigational GLP-RAs are listed in this paper. This review article will also explore common side effects and safety profiles of both long-acting and short-acting GLP-1 RAs. Additionally, it will highlight the recent advances and ongoing challenges in the field of drug discovery related to GLP-1 receptor agonists.
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Affiliation(s)
- Anukriti Saran
- Department of Bioscience and Biotechnology, Banasthali Vidyapith, Banasthali, Rajasthan, 304022, India.
| | - Riya Raisinghani
- Department of Bioscience and Biotechnology, Banasthali Vidyapith, Banasthali, Rajasthan, 304022, India
| | - Sarvesh Paliwal
- Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, 304022, India
| | - Swapnil Sharma
- Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, 304022, India
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Tanashat M, Al-Ajlouni YA, Abuelazm M, Altobaishat O, Manasrah A, Turkmani M, Khan U, Abouzid M. The Efficacy and Safety of GLP-1 RAs in the Modification of Cardiovascular Morbidity in Patients with Obesity Without Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials Involving 32,884 Patients. Am J Cardiovasc Drugs 2025:10.1007/s40256-025-00726-z. [PMID: 40246808 DOI: 10.1007/s40256-025-00726-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/18/2025] [Indexed: 04/19/2025]
Abstract
BACKGROUND Although the cardioprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are well documented in patients with diabetes mellitus, their impact on cardiovascular outcomes in patients with obesity without diabetes remains under debate. Therefore, we conducted this systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the effects of GLP-1 RAs on cardiovascular outcomes in patients with obesity without diabetes. METHODS We systematically searched PubMed, Web of Science, SCOPUS, and Cochrane databases through December 26, 2023. We pooled dichotomous data using risk ratios (RRs) and continuous data using mean differences with 95% confidence intervals (CIs). We evaluated the quality of each study using the Cochrane RoB2 method, and the study protocol was registered on PROSPERO ID: CRD42024498538. RESULTS We included 19 RCTs with a total of 32,884 patients. Of these, 15 had a low overall risk of bias, two raised concerns, and two had a high risk of bias. There was no difference between GLP-1 RAs and placebo regarding cardiovascular mortality (RR 0.85; 95% CI 0.71-1.01; p = 0.07). However, compared with placebo, GLP-1 RAs significantly decreased the incidence of all-cause mortality (RR 0.82; 95% CI 0.72-0.93; p < 0.0001), non-cardiovascular mortality (RR 0.77; 95% CI 0.63-0.95; p = 0.01), and myocardial infarction (RR 0.73; 95% CI 0.62-0.86; p < 0.0001). Additionally, patients receiving GLP-1 RAs experienced significant overall weight loss (- 8.53 kg; 95% CI - 12.38 to - 4.68; p < 0.0001) and improvements in lipid profiles, including lower levels of total cholesterol (- 0.77 %; 95% CI - 1.03 to - 0.50; p < 0.0001), triglycerides (- 6.78 %; 95% CI - 8.11 to - 5.46; p < 0.0001), low-density lipoproteins (- 2.85 %; 95% CI - 3.74 to - 1.96; p < 0.0001), and very low-density lipoproteins (- 4.47 %; 95% CI - 5.56 to - 3.38; p < 0.0001). GLP-1 RAs also significantly increased the incidence of any adverse events (RR 1.11; 95% CI 1.05-1.16; p < 0.0001), with no difference regarding the incidence of serious adverse events. However, gastrointestinal adverse events were significantly more frequent in patients receiving GLP-1 RAs, with a higher risk of any gastrointestinal adverse events (RR 2.83; 95% CI 1.86-4.3; p < 0.001), nausea (RR 2.70; 95% CI 2.18-3.33; p < 0.001), diarrhea (RR 1.97; 95% CI 1.68-2.31; p < 0.001), vomiting (RR 3.85; 95% CI 3.32-4.48; p < 0.001), and constipation (RR 2.35; 95% CI 1.94-2.85; p < 0.001) than in those receiving placebo. CONCLUSION In obese patients without diabetes, GLP-1 RAs demonstrated substantial benefits in reducing cardiovascular risks, including all-cause mortality and myocardial infarction, and effectively promoted weight loss and improved lipid profiles and blood pressure control. However, their use is accompanied by a higher incidence of gastrointestinal adverse effects and heterogeneity in outcomes, highlighting the need for individualized treatment approaches. REGISTRATION PROSPERO identifier number: CRD42024498538.
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Affiliation(s)
| | | | | | - Obieda Altobaishat
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Almothana Manasrah
- Department of Internal Medicine, United Health Services - Wilson Medical Center, Johnson city, NY, USA
| | - Mustafa Turkmani
- Faculty of Medicine, Michigan State University, East Lansing, MI, USA.
- Department of Internal Medicine, McLaren Health Care, Oakland, MI, USA.
| | - Ubaid Khan
- Division of Cardiology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Mohamed Abouzid
- Department of Physical Pharmacy and Pharmacokinetics, Faculty of Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3 St., 60-806, Poznan, Poland.
- Doctoral School, Poznan University of Medical Sciences, 60-812, Poznan, Poland.
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Merzeban DH, El Amin Ali AM, Hammad RO, Elmahdi MH, Sofi MA, Mahmoud RH, Metwally SM, El Ebiary AM. Differential effects of liraglutide naltrexone/bupropion, and caloric restriction on metabolic parameters and beta-cell regeneration in type 2 diabetic rat model: role of beta arrestin 1. J Mol Histol 2024; 56:50. [PMID: 39704859 DOI: 10.1007/s10735-024-10326-x] [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: 09/24/2024] [Accepted: 11/30/2024] [Indexed: 12/21/2024]
Abstract
Traditional antidiabetic treatments often carry the risk of beta-cell exhaustion, highlighting the need for therapies that promote beta-cell regeneration. This study investigates the comparative effects of Liraglutide, naltrexone/bupropion (NTX + BUP), and caloric restriction on metabolic control and beta-cell regeneration in a rat model of obese type 2 diabetes. Fifty male albino rats were randomized into five groups: normal control, diabetic control, diabetic + caloric restriction (50%), diabetic + NTX + BUP (4 mg/45 mg /kg/day orally), and diabetic + liraglutide (0.3 mg/kg/day, S.C). Body weight, BMI, serum glucose, insulin, lipid profile, atherogenic indices, beta-arrestin-1 levels, pancreatic histopathology, and immunohistochemical staining for insulin and Ki67 were assessed. All interventions significantly improved body weight, BMI, glycemic control, lipid profiles (except HDL), and atherogenic indices compared to the diabetic control group. NTX + BUP and caloric restriction resulted in greater weight loss compared to liraglutide. Of note, liraglutide significantly decreased β-arrestin-1 levels compared to both NTX + BUP and caloric restriction. Furthermore, liraglutide and caloric restriction significantly increased anti-insulin antibodies and Ki67 indicating beta-cell regeneration, while NTX + BUP showed insignificant effects. Thus we can conclude that, while NTX + BUP demonstrates efficacy in improving metabolic parameters in obese type 2 diabetic rats, it shows limitations in promoting beta-cell regeneration compared to liraglutide and caloric restriction.
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Affiliation(s)
- Dina H Merzeban
- The Departments of Medical Physiology, Faculty of Medicine, Fayoum University, Fayoum, Egypt.
| | - Amani M El Amin Ali
- The Departments of Medical Physiology, Faculty of Medicine, Fayoum University, Fayoum, Egypt
| | - Reem O Hammad
- The Departments of Medical Physiology, Faculty of Medicine, Fayoum University, Fayoum, Egypt
| | - Mohamed H Elmahdi
- The Departments of Anatomical Pathology, Faculty of Medicine, Fayoum University, Fayoum, Egypt
| | - Marwa A Sofi
- The Departments of Histology, Faculty of Medicine, Fayoum University, Fayoum, Egypt
| | - Rania H Mahmoud
- The Departments of Biochemistry and Molecular Biology, Fayoum University, Fayoum, Egypt
| | - Sayed M Metwally
- The Departments of Pharmacology and Toxicology, Faculty of Pharmacy, Fayoum University, Fayoum, Egypt
| | - Ahmed M El Ebiary
- The Departments of Medical Physiology, Faculty of Medicine, Fayoum University, Fayoum, Egypt
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Bykova A, Serova M, Chashkina M, Kosharnaya R, Salpagarova Z, Andreev D, Giverts I. Glucagon-like Peptide-1 Receptor Agonists in the Context of Pathophysiology of Diverse Heart Failure with Preserved Ejection Fraction Phenotypes: Potential Benefits and Mechanisms of Action. Card Fail Rev 2024; 10:e14. [PMID: 39507374 PMCID: PMC11539042 DOI: 10.15420/cfr.2024.06] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 06/26/2024] [Indexed: 11/08/2024] Open
Abstract
This review examines the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on different heart failure phenotypes with preserved ejection fraction (HFpEF). Traditional heart failure treatment modalities have shown limited success in improving outcomes for patients with HFpEF, but new evidence suggests that GLP-1RAs could be beneficial. The positive effects of GLP-1RAs are likely due to their ability to reduce systemic inflammation, enhance metabolism and directly affect the cardiovascular system, addressing critical aspects of HFpEF pathology. However, the exact impact of GLP-1RAs on clinical outcomes for different HFpEF phenotypes is still unclear. This review highlights both the potential benefits and the current limitations of GLP-1RA therapy, suggesting a careful approach for their application in clinical practice.
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Affiliation(s)
- Aleksandra Bykova
- Department of Cardiology, Functional and Ultrasound Diagnostics of NV Sklifosovsky Institute for Clinical Medicine, IM Sechenov First Moscow State Medical University (Sechenov University)Moscow, Russia
- Department of Medical Informatics, Scientific Research Institute for System Analysis of the Russian Academy of SciencesMoscow, Russia
| | - Maria Serova
- Department of Cardiology, Functional and Ultrasound Diagnostics of NV Sklifosovsky Institute for Clinical Medicine, IM Sechenov First Moscow State Medical University (Sechenov University)Moscow, Russia
- Department of Surgical Treatment of Complex Rhythm Disorders and Pacing, City Clinical Hospital No 1 Named after NI Pirogov, Moscow State Healthcare InstitutionMoscow, Russia
| | - Maria Chashkina
- Department of Cardiology, Functional and Ultrasound Diagnostics of NV Sklifosovsky Institute for Clinical Medicine, IM Sechenov First Moscow State Medical University (Sechenov University)Moscow, Russia
| | - Raisa Kosharnaya
- Department of Cardiology and Vascular Surgery, Endocrinology Research CentreMoscow, Russia
| | | | - Denis Andreev
- Department of Cardiology, Functional and Ultrasound Diagnostics of NV Sklifosovsky Institute for Clinical Medicine, IM Sechenov First Moscow State Medical University (Sechenov University)Moscow, Russia
| | - Ilya Giverts
- Department of Internal Medicine, Maimonides Medical CenterNew York, NY, US
- Cardiovascular Research Center, Massachusetts General Hospital BostonMA, US
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Tamayo-Trujillo R, Ruiz-Pozo VA, Cadena-Ullauri S, Guevara-Ramírez P, Paz-Cruz E, Zambrano-Villacres R, Simancas-Racines D, Zambrano AK. Molecular mechanisms of semaglutide and liraglutide as a therapeutic option for obesity. Front Nutr 2024; 11:1398059. [PMID: 38742021 PMCID: PMC11090168 DOI: 10.3389/fnut.2024.1398059] [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: 03/08/2024] [Accepted: 04/12/2024] [Indexed: 05/16/2024] Open
Abstract
Obesity, a chronic global health problem, is associated with an increase in various comorbidities, such as cardiovascular disease, type 2 diabetes mellitus, hypertension, and certain types of cancer. The increasing global prevalence of obesity requires research into new therapeutic strategies. Glucagon-like peptide-1 receptor agonists, specifically semaglutide and liraglutide, designed for type 2 diabetes mellitus treatment, have been explored as drugs for the treatment of obesity. This minireview describes the molecular mechanisms of semaglutide and liraglutide in different metabolic pathways, and its mechanism of action in processes such as appetite regulation, insulin secretion, glucose homeostasis, energy expenditure, and lipid metabolism. Finally, several clinical trial outcomes are described to show the safety and efficacy of these drugs in obesity management.
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Affiliation(s)
- Rafael Tamayo-Trujillo
- Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador
| | - Viviana A. Ruiz-Pozo
- Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador
| | - Santiago Cadena-Ullauri
- Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador
| | - Patricia Guevara-Ramírez
- Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador
| | - Elius Paz-Cruz
- Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador
| | | | - Daniel Simancas-Racines
- Centro de Investigación de Salud Pública y Epidemiología Clínica (CISPEC), Universidad UTE, Quito, Ecuador
| | - Ana Karina Zambrano
- Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador
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Wang T, Ding J, Cheng X, Yang Q, Hu P. Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease. Front Pharmacol 2024; 15:1396656. [PMID: 38720777 PMCID: PMC11076696 DOI: 10.3389/fphar.2024.1396656] [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: 03/06/2024] [Accepted: 04/11/2024] [Indexed: 05/12/2024] Open
Abstract
Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of cardiovascular mortality and is increasingly prevalent in our population. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can safely and effectively lower glucose levels while concurrently managing the full spectrum of ASCVD risk factors and improving patients' long-term prognosis. Several cardiovascular outcome trials (CVOTs) have been carried out to further investigate the cardiovascular benefits of GLP-1RAs. Analyzing data from CVOTs can provide insights into the pathophysiologic mechanisms by which GLP-1RAs are linked to ASCVD and define the use of GLP-1RAs in clinical practice. Here, we discussed various mechanisms hypothesized in previous animal and preclinical human studies, including blockade of the production of adhesion molecules and inflammatory factors, induction of endothelial cells' synthesis of nitric oxide, protection of mitochondrial function and restriction of oxidative stress, suppression of NOD-like receptor thermal protein domain associated protein three inflammasome, reduction of foam cell formation and macrophage inflammation, and amelioration of vascular smooth muscle cell dysfunction, to help explain the cardiovascular benefits of GLP-1RAs in CVOTs. This paper provides an overview of the clinical research, molecular processes, and possible therapeutic applications of GLP-1RAs in ASCVD, while also addressing current limitations in the literature and suggesting future research directions.
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Affiliation(s)
- Tianyu Wang
- Department of The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Juncan Ding
- Department of The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xinyi Cheng
- Department of The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Qiang Yang
- Department of The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Pengfei Hu
- Department of Cardiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
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Alsheikh A, Alshehri A, Alzahrani S, Jammah AA, Alqahtani F, Alotaibi M, Aldahash R, Alhozali AM, Alsabaan F, Almehthel M, Aljuhani N, Aldabeis A, Alamri M, Maghawry W, Alzaman N, Alshaikh A, M Alnozha O, Issak ER, Alsifri S. Evaluating the Clinical Effectiveness and Safety of Semaglutide in Individuals with Uncontrolled Type 2 Diabetes. Real-World Evidence from Saudi Arabia: The Observational, Multicenter, 15-Month EVOLUTION Study. Diabetes Ther 2024; 15:473-485. [PMID: 38110660 PMCID: PMC10838866 DOI: 10.1007/s13300-023-01516-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 11/23/2023] [Indexed: 12/20/2023] Open
Abstract
INTRODUCTION This study aimed to assess the safety and effectiveness of semaglutide, administered either by weekly subcutaneous (SC) injection or orally, in real-life practice in Saudi Arabia in individuals with type 2 diabetes mellitus (T2DM). METHODS A retrospective chart review study was conducted at 18 Saudi Arabia centers. An accredited centralized institutional review board approved the study. Medical records were included for individuals of any age ≥ 18 years with uncontrolled T2DM. The primary outcome measure was the laboratory glycated hemoglobin (HbA1c) level. Secondary measures included fasting blood glucose (FBG), weight, and hypoglycemia. All variables were checked after 6 and 12 months of semaglutide initiation. RESULTS The analysis of this study included 1223 patients with uncontrolled T2DM (HbA1c > 7%). The mean (SD) baseline HbA1c was 10.02% (1.17). HbA1c was reduced by an average of 3.02% (0.84) and 3.17% (0.84) at 6 and 12 months, respectively. Results of a repeated measure analysis of variance (ANOVA) indicated significant differences in HbA1c (p value < 0.001). HbA1c levels at 6 and 12 months were significantly lower, 7.00% (0.70) and 6.85% (0.69), than at baseline, 10.02% (1.17). About 193 patients (56.4%) of the 295 patients having HbA1c < 9% achieved HbA1c of 5.7% or less. The frequency of hypoglycemia events was 4.60 (1.10) in the 3 months before semaglutide was initiated. The frequency of hypoglycemia events in the last 3 months was 2.30 (0.80) events and 0.80 (0.50) events at 6-month and 12-month follow-up visits, respectively. The percent reduction in body mass index (BMI) was an average of 13.07% (1.53) and 19.89% (4.07) at 6 and 12 months, respectively. Lipid profile and blood pressure were improved at 6 and 12 months. CONCLUSION Semaglutide, administered either by SC injection or orally, provided substantial glycemic and weight-loss benefits in adults with T2DM.
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Affiliation(s)
- Abdulrahman Alsheikh
- King Abdulaziz University Hospital, Jeddah, Saudi Arabia
- Dr. Suliman Fakeeh Hospital, Jeddah, Saudi Arabia
| | | | | | - Anwar A Jammah
- King Saud University Medical City, Riyadh, Saudi Arabia
- Alhammadi Hospital, Riyadh, Saudi Arabia
| | | | - Metib Alotaibi
- Alhammadi Hospital, Riyadh, Saudi Arabia
- Dr Suliman Alhabeeb Hospital, Alolya, Riyadh, Saudi Arabia
| | - Raed Aldahash
- Dr Suliman Alhabeeb Hospital, Alolya, Riyadh, Saudi Arabia
- King Abdallah Medical City, National Guard, Riyadh, Saudi Arabia
| | - Amani M Alhozali
- King Abdulaziz University Hospital, Jeddah, Saudi Arabia
- International Medical Center, Jeddah, Saudi Arabia
| | | | | | | | | | - Moneer Alamri
- Southern Armed Forces Hospital, Khamis Mushait, Saudi Arabia
| | | | - Naweed Alzaman
- Department of Medicine, College of Medicine, Taibah University, Madinah, Saudi Arabia
- Madina Medical Center, Madinah, Saudi Arabia
| | | | - Omar M Alnozha
- Department of Medicine, College of Medicine, Taibah University, Madinah, Saudi Arabia
- Saudi German Hospital, Madinah, Saudi Arabia
| | - Emad R Issak
- Department of Internal Medicine, Ain Shams University, Cairo, Egypt.
| | - Saud Alsifri
- Alhada Armed Forces Hospital, Taif, Saudi Arabia
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Martinka E, Dravecká I, Tkáč I. Switching from Multiple Insulin Injections to a Fixed Combination of Degludec and Liraglutide in Patients with Type 2 Diabetes Mellitus: Results from the Simplify Study After 6 Months. Diabetes Ther 2023:10.1007/s13300-023-01435-z. [PMID: 37402960 PMCID: PMC10363096 DOI: 10.1007/s13300-023-01435-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 06/12/2023] [Indexed: 07/06/2023] Open
Abstract
INTRODUCTION This study aimed to evaluate the effectiveness and safety of switching from basal bolus insulin treatment (BBIT) to a fixed combination of insulin degludec and liraglutide (IDegLira) in patients with type 2 diabetes mellitus (T2DM) who had preserved insulin secretion but inadequate glucose control. The study also aimed to assess the feasibility of implementing this therapeutic approach in common clinical practice settings. METHODS This was a non-randomized, open-label, multicenter, prospective, single-arm study involving 234 patients with T2DM who were receiving BBIT. Inclusion criteria were duration of diabetes mellitus > 60 months, stable total daily dose of insulin (TDDI) ranging from > 20 to < 70 IU/day (approx. > 0.3 to < 0.7 IU/kg body weight/day), C-peptide levels > 10% above the lower limit, HbA1c levels > 7% and < 10% (Diabetes Control and Complications Trial), and body mass index > 25 kg/m2. The primary endpoints were changes in glycated hemoglobin (HbA1c) and body weight at week 28 after treatment switching. Secondary endpoints included changes in the 7-point glycemic profile, hypoglycemia frequency, blood pressure, blood lipids, liver enzymes, insulin dose, and a patient questionnaire focusing on treatment satisfaction, concerns and impact on daily activities. A subgroup of 55 patients underwent continuous glucose monitoring (CGM) with the evaluation of CGM-derived parameters, such as time in range (TIR), time above range (TAR), time below range (TBR), hypoglycemia, and glucose variability. RESULTS A significant decrease in HbA1c (8.6% vs. 7.6%; p < 0.0001) and body weight (97.8 vs. 94.0 kg; p < 0.0001) was observed at week 28 after treatment switching. Significant improvements were also seen in all measurements of the 7-point glycemic profile (p < 0.0001), reduction in the number of hypoglycemia episodes per patient, and the proportion of patients with at least one hypoglycemia event (p < 0.001). Furthermore, there was a significant decrease in daily insulin dose (55.6 vs. 32.7 IU/day; p < 0.0001), as well as improvements in blood pressure, blood lipids, and liver enzymes (gamma glutamyl transferase and alanine aminotransferase). The subgroup of patients who underwent CGM showed a significant increase in TIR (57.9% vs. 69.0%; p < 0.01) and a decrease in TAR (40.1% vs. 28.8%; p < 0.01), while TBR, hypoglycemia (number of episodes per patient and proportion of patients), and glucose variability did not change significantly. CONCLUSION The results of this study suggest that switching from BBIT to IDegLira in patients with T2DM and preserved insulin secretion can simplify treatment without compromising glycemic control. The switch to IDegLira was associated with significant improvements in various glucose control parameters, including HbA1c, glycemic profile, hypoglycemia, insulin doses, and CGM-derived parameters TIR and TAR. Additionally, it led to significant reductions in body weight, blood pressure, lipid profile, and liver enzyme levels. Switching to IDegLira may be considered a safe and beneficial approach in clinical practice settings, offering metabolic and individual advantages.
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Affiliation(s)
- Emil Martinka
- National Institute of Endocrinology and Diabetology, Ľubochňa, Slovakia.
| | - Ingrid Dravecká
- Department of Internal Medicine 1, Faculty of Medicine, P.J. Šafárik University-L. Pasteur University Hospital, Košice, Slovakia
| | - Ivan Tkáč
- Department of Internal Medicine 4, Faculty of Medicine, P.J. Šafárik University-L. Pasteur University Hospital, Košice, Slovakia
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Arvanitakis K, Koufakis T, Popovic D, Maltese G, Mustafa O, Doumas M, Giouleme O, Kotsa K, Germanidis G. GLP-1 Receptor Agonists in Obese Patients with Inflammatory Bowel Disease: from Molecular Mechanisms to Clinical Considerations and Practical Recommendations for Safe and Effective Use. Curr Obes Rep 2023; 12:61-74. [PMID: 37081371 DOI: 10.1007/s13679-023-00506-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/09/2023] [Indexed: 04/22/2023]
Abstract
PURPOSE OF REVIEW To discuss current literature and provide practical recommendations for the safe and effective use of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in people with inflammatory bowel disease (IBD) and type 2 diabetes (T2D) and/or obesity. The molecular mechanisms that justify the potential benefits of GLP-1 RA in IBD and the links between IBD, obesity, and cardiovascular disease are also discussed. RECENT FINDINGS Preliminary data suggest that GLP-1 RA can modulate crucial pathways in the pathogenesis of IBD, such as chronic inflammation circuits, intestinal tight junctions, and gut microbiome dysbiosis, setting the stage for human trials to investigate the role of these agents in the treatment of IBD among people with or without diabetes and obesity. However, gastrointestinal side effects related to GLP-1 RA need appropriate clinical management to mitigate risks and maximize the benefits of therapy in people with IBD. GLP-1 RA originally emerged as drugs for the treatment of hyperglycemia and are currently licensed for the management of T2D and/or overweight/obesity. However, their wealth of pleiotropic actions soon raised expectations that they might confer benefits on non-metabolic disorders. Future studies are expected to clarify whether GLP-1 RA deserve an adjunct place in the arsenal of drugs against IBD.
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Affiliation(s)
- Konstantinos Arvanitakis
- Division of Gastroenterology and Hepatology, First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece
- Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636, Thessaloniki, Greece
| | - Theocharis Koufakis
- Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
| | - Djordje Popovic
- Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre of Vojvodina, Medical Faculty, University of Novi Sad, Novi Sad, Serbia
| | - Giuseppe Maltese
- Department of Diabetes and Endocrinology, Epsom & St Helier University Hospitals, Surrey, SM5 1AA, UK
- Unit for Metabolic Medicine, Cardiovascular Division, Faculty of Life Sciences & Medicine, King's College, London, UK
| | - Omar Mustafa
- Department of Diabetes, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
- King's College London, London, UK
| | - Michael Doumas
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Olga Giouleme
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Kalliopi Kotsa
- Division of Endocrinology and Metabolism and Diabetes Centre, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
| | - Georgios Germanidis
- Division of Gastroenterology and Hepatology, First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636, Thessaloniki, Greece.
- Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636, Thessaloniki, Greece.
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11
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Cigrovski Berkovic M, Strollo F. Semaglutide-eye-catching results. World J Diabetes 2023; 14:424-434. [PMID: 37122431 PMCID: PMC10130900 DOI: 10.4239/wjd.v14.i4.424] [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: 12/15/2022] [Revised: 02/08/2023] [Accepted: 03/20/2023] [Indexed: 04/12/2023] Open
Abstract
Semaglutide is a glucagon-like peptide-1 receptor agonist used either orally every day or subcutaneously once a week for the treatment of type 2 diabetes mellitus and, more recently, at higher doses, for the treatment of obesity. Both diseases are reaching epidemic proportions and often coexist, posing patients with a high risk for cardiovascular disease and death. Therefore, an agent such as semaglutide, which offers clinically significant weight loss and cardiovascular benefits, is essential and will be increasingly used in high-risk patients. However, during the SUSTAIN clinical trial program (Semaglutide Unabated Sustainability in treat-ment of type 2 diabetes), a safety issue concerning the progression and worsening of diabetic retinopathy emerged. The existing explanation so far mainly supports the role of the magnitude and speed of HbA1c reduction, a phenomenon also associated with insulin treatment and bariatric surgery. Whether and to which extent the effect is direct is still a matter of debate and an intriguing topic to investigate for suitable preventative and rehabilitative purposes. In this minireview, we will summarize the available data and suggest guidelines for a comprehensive semaglutide clinical utilization until new evidence becomes available.
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Affiliation(s)
| | - Felice Strollo
- Department of Endocrinology and Metabolism, IRCCS San Raffaele Pisana, Rome 00163, Italy
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12
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Jobanputra R, Sargeant JA, Almaqhawi A, Ahmad E, Arsenyadis F, Webb DR, Herring LY, Khunti K, Davies MJ, Yates T. The effects of weight-lowering pharmacotherapies on physical activity, function and fitness: A systematic review and meta-analysis of randomized controlled trials. Obes Rev 2023; 24:e13553. [PMID: 36721366 DOI: 10.1111/obr.13553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 12/16/2022] [Accepted: 01/11/2023] [Indexed: 02/02/2023]
Abstract
Weight-lowering pharmacotherapies provide an option for weight management; however, their effects on physical activity, function, and cardiorespiratory fitness are not fully understood. We conducted a systematic review and meta-analysis of randomized controlled trials to investigate the effect of licensed weight loss pharmacotherapies on physical activity, physical function, and cardiorespiratory fitness in individuals with obesity. Fourteen trials met our prespecified inclusion criteria: Five investigated liraglutide, four semaglutide, three naltrexone/bupropion, and two phentermine/topiramate. All 14 trials included a self-reported measure of physical function, with the pooled findings suggesting an improvement favoring the pharmacotherapy intervention groups (SMD: 0.27; 95% CI: 0.22 to 0.32) and effects generally consistent across different therapies. Results were also consistent when stratified by the two most commonly used measures: The Short-Form 36-Item Questionnaire (SF-36) (0.24; 0.17 to 0.32) and the Impact of Weight on Quality Of Life-Lite (IWQOL-Lite) (0.29; 0.23 to 0.35). Meta-regression confirmed a significant association between pharmacotherapy induced weight loss and improved physical function for IWQOL-Lite (p = 0.003). None of the studies reported a physical activity outcome, and only one study reported objectively measured cardiorespiratory fitness. Improvements in self-reported physical function were observed with weight loss therapy, but the effect on physical activity or objectively measured physical function and fitness could not be determined.
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Affiliation(s)
- Rishi Jobanputra
- Diabetes Research Centre, University of Leicester, Leicester, UK.,National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK.,Department of Health Sciences, University of Leicester, Leicester, UK
| | - Jack A Sargeant
- Diabetes Research Centre, University of Leicester, Leicester, UK.,National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
| | - Abdullah Almaqhawi
- Diabetes Research Centre, University of Leicester, Leicester, UK.,National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK.,Department of Family and Community Medicine, College Of Medicine, King Faisal University, Dammam, Saudi Arabia
| | - Ehtasham Ahmad
- Diabetes Research Centre, University of Leicester, Leicester, UK.,National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
| | - Franciskos Arsenyadis
- Diabetes Research Centre, University of Leicester, Leicester, UK.,National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
| | - David R Webb
- Diabetes Research Centre, University of Leicester, Leicester, UK.,National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
| | - Louisa Y Herring
- Diabetes Research Centre, University of Leicester, Leicester, UK.,National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester, UK.,National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK.,NIHR Applied Research Collaboration East Midlands, Leicester, UK
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester, Leicester, UK.,National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
| | - Thomas Yates
- Diabetes Research Centre, University of Leicester, Leicester, UK.,National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and the University of Leicester, Leicester, UK
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13
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Alkhezi OS, Alahmed AA, Alfayez OM, Alzuman OA, Almutairi AR, Almohammed OA. Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: A network meta-analysis of randomized clinical trials. Obes Rev 2023; 24:e13543. [PMID: 36579723 DOI: 10.1111/obr.13543] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 10/09/2022] [Accepted: 12/06/2022] [Indexed: 12/30/2022]
Abstract
Tirzepatide is a new glucagon-like peptide-1 receptor agonist (GLP-1RA) that has shown promising results for weight loss. A Bayesian network meta-analysis was conducted to compare the efficacy and safety of GLP-1RAs for obesity management. Embase and MEDLINE were searched looking for randomized clinical trials (RCTs) that evaluated the efficacy of GLP-1RAs for weight loss in patients without diabetes. The main efficacy outcomes evaluated were the mean change in actual and percentage weight loss and the proportion of patients with weight loss of ≥5%-20%. Main safety outcomes evaluated include nausea, vomiting, diarrhea, constipation, loss of appetite, pancreatitis, gallbladder-related disorders, and withdrawal due to adverse events. Seven RCTs with more than 12,300 patients were analyzed, including patients with body mass index (BMI) ≥ 30 kg/m2 , or BMI ≥ 27 kg/m2 with comorbidities. Weekly tirzepatide 10 and 15 mg resulted in more weight loss than weekly semaglutide 2.4 mg, daily semaglutide 0.4 mg, or liraglutide 3 mg. Tirzepatide and weekly semaglutide demonstrated comparable results but with significantly higher odds of achieving ≥5%-20% weight loss compared with liraglutide. GLP-1RAs triggered more gastrointestinal adverse events than placebo, with no in-between difference. Although all GLP-1RAs lead to significant weight reduction, tirzepatide was associated with better efficacy outcomes while having a comparable safety profile.
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Affiliation(s)
- Omar S Alkhezi
- Department of Pharmacy Services, Brigham and Women's Hospital, Boston, Massachusetts, USA
- Department of Pharmacy Practice, Unaizah College of Pharmacy, Qassim University, Qassim, Saudi Arabia
| | - Abdullah A Alahmed
- Department of Pharmacy Services, Brigham and Women's Hospital, Boston, Massachusetts, USA
- Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim, Saudi Arabia
| | - Osamah M Alfayez
- Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim, Saudi Arabia
| | - Osama A Alzuman
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | | | - Omar A Almohammed
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
- Pharmacoeconomics Research Unit, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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14
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Zhao L, Qiu Y, Zhang P, Wu X, Zhao Z, Deng X, Yang L, Wang D, Yuan G. Gut microbiota mediates positive effects of liraglutide on dyslipidemia in mice fed a high-fat diet. Front Nutr 2022; 9:1048693. [PMID: 36643973 PMCID: PMC9835552 DOI: 10.3389/fnut.2022.1048693] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 11/14/2022] [Indexed: 12/30/2022] Open
Abstract
Except for improving glycemic control, liraglutide, one of the glucagon-like peptide-1 receptor agonists, has exerted promising therapeutic effects for dyslipidemia. It has been proved that gut microbiota plays a dramatic role in regulating lipid metabolism. This study aims to explore whether liraglutide could improve dyslipidemia by modulating the gut microbiota in mice fed a high-fat diet (HFD). The C57BL/6 mice were fed a HFD to establish an animal model of dyslipidemia, and then administered with liraglutide or normal saline (NS) for 12 weeks. Indices of glucolipid metabolism were evaluated. Gut microbiota of the mice was analyzed by 16S rRNA gene sequencing. Compared with HFD group, liraglutide significantly alleviated weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels, meanwhile elevating high-density lipoprotein cholesterol (HDL) levels (all p < 0.05). The gut microbiota analysis revealed that liraglutide greatly reduced the relative abundance of Firmicutes and augmented that of Bacteroidetes, with a concomitant drop in the Firmicutes/Bacteroidetes ratio. Meanwhile, liraglutide dramatically changed the overall composition, promoted the growth of beneficial microbes (Akkermansia, Lactobacillus, Parabacteroides, Oscillospira, etc.), and inhibited the growth of harmful microbes (AF12, Shigella, Proteobacteria, Xenorhabdus, etc.). Especially, the relative abundance of Akkermansia increased the most after liraglutide treatment. Correlation analysis suggested that TC and LDL were positively correlated with some harmful bacteria, and negatively associated with beneficial bacteria. This study confirmed that liraglutide had a certain therapeutic effect on dyslipidemia in HFD-fed mice and could regulate the composition of the gut microbiota associated with lipid metabolism, especially Akkermansia. Thus, affecting gut microbiota might be a potential mechanism of liraglutide in attenuating dyslipidemia.
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Affiliation(s)
- Li Zhao
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China,*Correspondence: Li Zhao,
| | - Yue Qiu
- Department of Endocrinology and Metabolism, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu, China
| | - Panpan Zhang
- Department of Endocrinology, Taicang Hospital of Traditional Chinese Medicine, Taicang, Jiangsu, China
| | - Xunan Wu
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Zhicong Zhao
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Xia Deng
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Ling Yang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Dong Wang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Guoyue Yuan
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China,Guoyue Yuan,
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15
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Sang H, Wan Y, Ma Z, Zhang S, Zhao Q. Cost-effectiveness of empagliflozin for the treatment of heart failure with reduced ejection fraction in China. Front Cardiovasc Med 2022; 9:1022020. [PMID: 36465457 PMCID: PMC9708714 DOI: 10.3389/fcvm.2022.1022020] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 11/01/2022] [Indexed: 09/01/2023] Open
Abstract
AIM To determine the pharmacoeconomics of empagliflozin for the treatment of heart failure (HF) with reduced ejection fraction in China and to provide evidence-based reference for clinical rational drug selection and medical decision-making. RESEARCH DESIGN AND METHODS We used the Markov model to evaluate the cost-effectiveness of empagliflozin for the treatment of HF with reduced ejection fraction (HFrEF). We evaluated the cost-effectiveness of the standard treatment in addition to empagliflozin (empagliflozin group) vs. the cost-effectiveness of the standard treatment alone (standard treatment group). RESULTS We found that each additional quality-adjusted life year (QALY) in the empagliflozin group costed $3,842.20 more, which was less than China's gross domestic product (GDP) per capita in 2021 ($11,981). The steady-state mortality in the two groups was the key factor affecting the incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analysis revealed that when the willingness-to-pay (WTP) threshold was one time the GDP per capita in 2021 ($11,981) and three times the GDP per capita in 2021 ($35,943), the probability of the empagliflozin group being cost-effective was 85.8 and 91.6%, respectively. CONCLUSION Compared with the standard treatment alone, the addition of empagliflozin to the standard treatment was more cost-effective for the treatment of HFrEF in China.
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Affiliation(s)
- Haiqiang Sang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yiming Wan
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhenzhou Ma
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shengye Zhang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qiuping Zhao
- Department of Cardiology, Fuwai Central China Cardiovascular Hospital, Zhengzhou, China
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16
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Pinto G, Fragasso G. Aortic valve stenosis: drivers of disease progression and drug targets for therapeutic opportunities. Expert Opin Ther Targets 2022; 26:633-644. [DOI: 10.1080/14728222.2022.2118576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
- Giuseppe Pinto
- Departmen of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy
| | - Gabriele Fragasso
- Department of Clinical Cardiology, Heart Failure Clinic, IRCCS San Raffaele Scientific Institute, Milano
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17
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Mahapatra MK, Karuppasamy M, Sahoo BM. Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes. Rev Endocr Metab Disord 2022; 23:521-539. [PMID: 34993760 PMCID: PMC8736331 DOI: 10.1007/s11154-021-09699-1] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/27/2021] [Indexed: 11/22/2022]
Abstract
Semaglutide, a glucagon like peptide-1 (GLP-1) receptor agonist, is available as monotherapy in both subcutaneous as well as oral dosage form (first approved oral GLP-1 receptor agonist). It has been approved as a second line treatment option for better glycaemic control in type 2 diabetes and currently under scrutiny for anti-obesity purpose. Semaglutide has been proved to be safe in adults and elderly patients with renal or hepatic disorders demanding no dose modification. Cardiovascular (CV) outcome trials established that it can reduce various CV risk factors in patients with established CV disorders. Semaglutide is well tolerated with no risk of hypoglycaemia in monotherapy but suffers from gastrointestinal adverse effects. A large population affected with COVID-19 infection were diabetic; therefore use of semaglutide in diabetes as well as CV patients would be very much supportive in maintaining health care system during this pandemic situation. Hence, this peptidic drug can be truly considered as a quintessential of GLP-1 agonists for management of type 2 diabetes.
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Affiliation(s)
- Manoj Kumar Mahapatra
- Kanak Manjari Institute of Pharmaceutical Sciences, Rourkela, 769015, Odisha, India.
| | - Muthukumar Karuppasamy
- YaAn Pharmaceutical and Medical Communications, 6/691H1, Balaji Nagar, Sithurajapuram, Sivakasi, 626189, Tamilnadu, India
| | - Biswa Mohan Sahoo
- Roland Institute of Pharmaceutical Sciences, Berhampur, 760010, Odisha, India
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18
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Di Loreto C, Minarelli V, Nasini G, Norgiolini R, Del Sindaco P. Effectiveness in Real World of Once Weekly Semaglutide in People with Type 2 Diabetes: Glucagon-Like Peptide Receptor Agonist Naïve or Switchers from Other Glucagon-Like Peptide Receptor Agonists: Results from a Retrospective Observational Study in Umbria. Diabetes Ther 2022; 13:551-567. [PMID: 35230650 PMCID: PMC8886341 DOI: 10.1007/s13300-022-01218-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 02/01/2022] [Indexed: 12/28/2022] Open
Abstract
INTRODUCTION To complement results of the SUSTAIN program, this study assessed effectiveness and safety of once weekly subcutaneous semaglutide in people with type 2 diabetes (T2D) managed under routine care. METHODS This was a multicenter, observational, retrospective study including all patients treated with semaglutide. Changes in clinical outcomes from baseline to 6 and 12 months were assessed in patients who were glucagon-like peptide receptor agonist (GLP-1RA) naïve or switching from another GLP-1RA. Discontinuation rate was assessed. RESULTS Overall, 216 patients (mean age 64 years, 65.7% men) were evaluated: 135 (61.5%) naïve and 81 (38.5%) switchers from another GLP-1RA. In the naïve cohort, after 6 months from semaglutide initiation, levels of HbA1c significantly decreased by - 1.31% (p < 0.0001). All obesity indices improved, with mean reductions in body weight of - 3.92 kg, in BMI of - 1.43 kg/m2, and in waist circumference of - 5.03 cm. In the switcher cohort, statistically significant improvements in HbA1c (- 0.78%), body weight (- 2.64 kg), and waist circumference (- 3.03 cm) were obtained after 6 months. Reductions were sustained after 12 months in both cohorts (mean semaglutide dose: 0.86 mg in naïve and 0.96 mg in switcher cohort). Blood pressure and lipid profile mean levels decreased after 12 months from semaglutide initiation in both cohorts. No severe hypoglycemia occurred; 6.5% of patients discontinued semaglutide (2.8% due to gastrointestinal side effects). CONCLUSION Effectiveness and tolerability of semaglutide have been confirmed in the real world irrespective of diabetes duration and severity. As expected, more marked reductions in HbA1c and obesity indices were obtained in naïve patients, but it is noteworthy that relevant improvements were also obtained in patients already treated with GLP-1RAs.
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Affiliation(s)
- Chiara Di Loreto
- Diabetes Clinic, USL Umbria 1, Perugia Territorial Health Structure, Perugia, Italy.
| | - Viviana Minarelli
- Diabetes Clinic, USL Umbria 1, Città di Castello Hospital, Città di Castello, Italy
| | - Giovanni Nasini
- Diabetes Clinic, USL Umbria 1, Castiglione del Lago Hospital District, Castiglione del Lago, Italy
| | - Roberto Norgiolini
- Diabetes Clinic, USL Umbria 1, Città di Castello Hospital, Città di Castello, Italy
| | - Paola Del Sindaco
- Diabetes Clinic, USL Umbria 1, Perugia Territorial Health Structure, Perugia, Italy
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19
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Gembillo G, Cernaro V, Giuffrida AE, Russo G, Giandalia A, Siligato R, Longhitano E, Santoro D. Gender differences in new hypoglycemic drug effects on renal outcomes: a systematic review. Expert Rev Clin Pharmacol 2022; 15:323-339. [PMID: 35300556 DOI: 10.1080/17512433.2022.2055546] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 01/28/2022] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Lifetime diabetes risk is greater in women than in men. Women with diabetes mellitus (DM) have a greater prevalence of diabetic kidney disease (DKD) risk factors. The diagnosis of DM is often delayed in women, with poorer outcomes and with expected therapeutic goals missed. AREA COVERED A systematic literature review following PRISMA guidelines was conducted in the PubMed gateway of the MEDLINE database and Clinicaltrials.gov. The purpose of our research was to establish the sex differences on renal outcomes in users of the new hypoglycemic drugs: sodium-glucose transport protein 2 inhibitors (SGLT-2i), dipeptidyl peptidase-IV Inhibitors (DPP-IVi) and glucagon-like peptide-1 inhibitors (GLP-1i). EXPERT OPINION New hypoglycemic drugs represent promising tools in the treatment and prevention of severe complications of diabetes, cardiovascular diseases and chronic kidney disease. Even if renal outcomes are investigated in both randomized controlled trials and cardiovascular outcome trials, gender-based analysis is not always performed. Our systematic review demonstrated that the gap among sexes in DKD can be partially filled using new hypoglycemic drugs. Sexual dimorphism analysis could represent a keystone for the development of adequate gender-specific therapies.
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Affiliation(s)
- Guido Gembillo
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Messina Italy
- Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Italy
| | - Valeria Cernaro
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Messina Italy
| | - Alfio Edoardo Giuffrida
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Messina Italy
| | - Giuseppina Russo
- Department of Clinical and Experimental Medicine, University of Messina, Messina Italy
| | - Annalisa Giandalia
- Department of Clinical and Experimental Medicine, University of Messina, Messina Italy
| | - Rossella Siligato
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Messina Italy
| | - Elisa Longhitano
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Messina Italy
| | - Domenico Santoro
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Messina Italy
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20
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Tuculina M, Perlea P, Gheorghiță M, Cumpătă C, Dascălu I, Turcu A, Nicola A, Gheorghiță L, Diaconu O, Valea A, Ghemigian A, Carsote M. Diabetes mellitus: Plasticizers and nanomaterials acting as endocrine‑disrupting chemicals (Review). Exp Ther Med 2022; 23:288. [DOI: 10.3892/etm.2022.11217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 11/18/2021] [Indexed: 11/06/2022] Open
Affiliation(s)
- Mihaela Tuculina
- Department of Orthodontics, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Paula Perlea
- Department of Endodontology, Faculty of Dental Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Mircea Gheorghiță
- Department of Orthodontics, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Cristian Cumpătă
- Faculty of Dental Medicine, ‘Titu Maiorescu’ University of Bucharest, 031593 Bucharest, Romania
| | - Ionela Dascălu
- Department of Orthodontics, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Adina Turcu
- Department of Orthodontics, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Andreea Nicola
- Department of Orthodontics, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Lelia Gheorghiță
- Department of Orthodontics, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Oana Diaconu
- Department of Orthodontics, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Ana Valea
- Departement of Endocrinology, ‘Iuliu Hatieganu’ University of Medicine and Pharmacy, 400337 Cluj‑Napoca, Romania
| | - Adina Ghemigian
- Department of Endocrinology, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Mara Carsote
- Department of Endocrinology, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
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21
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Liu C, Liu Y, Xin Y, Wang Y. Circadian secretion rhythm of GLP-1 and its influencing factors. Front Endocrinol (Lausanne) 2022; 13:991397. [PMID: 36531506 PMCID: PMC9755352 DOI: 10.3389/fendo.2022.991397] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 11/22/2022] [Indexed: 12/04/2022] Open
Abstract
Circadian rhythm is an inherent endogenous biological rhythm in living organisms. However, with the improvement of modern living standards, many factors such as prolonged artificial lighting, sedentarism, short sleep duration, intestinal flora and high-calorie food intake have disturbed circadian rhythm regulation on various metabolic processes, including GLP-1 secretion, which plays an essential role in the development of various metabolic diseases. Herein, we focused on GLP-1 and its circadian rhythm to explore the factors affecting GLP-1 circadian rhythm and its potential mechanisms and propose some feasible suggestions to improve GLP-1 secretion.
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22
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Ding LN, Ding WY, Ning J, Wang Y, Yan Y, Wang ZB. Effects of Probiotic Supplementation on Inflammatory Markers and Glucose Homeostasis in Adults With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Front Pharmacol 2021; 12:770861. [PMID: 34955840 PMCID: PMC8706119 DOI: 10.3389/fphar.2021.770861] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 11/23/2021] [Indexed: 12/21/2022] Open
Abstract
Background: Several studies have revealed the effect of probiotic supplementation in patients with type 2 diabetes (T2DM) on the amelioration of low-grade inflammation, which plays an important role in the pathogenesis of T2DM. However, the effects of the clinical application of probiotics on inflammation in individuals with T2DM remain inconsistent. This study aims to investigate the comprehensive effects of probiotics on inflammatory markers in adults with T2DM. Methods: PubMed, Embase, Cochrane Library, and the Web of Science were searched to identify randomized controlled trials (RCTs) exploring the effect of probiotic supplementation on inflammatory markers in individuals with T2DM through March 11, 2021. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. We used a random-effects model to calculate the standardized mean difference (SMD) between the probiotic supplementation and control groups. Results: Seventeen eligible studies were selected with a total of 836 participants, including 423 participants in probiotic supplementation groups and 413 participants in control groups. Our study demonstrated that compared with the control condition, probiotic intake produced a beneficial effect in reducing the levels of plasma inflammation markers, including tumour necrosis factor-α (TNF-α) (SMD [95% CI]; −0.37 [−0.56, −0.19], p < 0.0001) and C-reactive protein (CRP) (SMD [95% CI]; −0.21 [−0.42, −0.01], p = 0.040), while it had no effect on the plasma interleukin-6 (IL-6) level (SMD [95% CI]; −0.07 [−0.27, 0.13], p = 0.520). In addition, our results support the notion that probiotic supplementation improves glycaemic control, as evidenced by a significant reduction in fasting blood glucose (FPG), HbA1c and HOMA-IR (SMD [95% CI]: −0.24 [−0.42, −0.05], p = 0.010; −0.19 [−0.37, −0.00], p = 0.040; −0.36 [−0.62, −0.10], p = 0.006, respectively). Conclusion: Our study revealed some beneficial effects of probiotic supplementation on improving inflammatory markers and glucose homeostasis in individuals with T2DM. Probiotics might be a potential adjuvant therapeutic approach for T2DM.
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Affiliation(s)
- Li-Na Ding
- Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.,Shandong Institute of Endocrine and Metabolic Diseases, Jinan, China
| | - Wen-Yu Ding
- Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.,Shandong Institute of Endocrine and Metabolic Diseases, Jinan, China
| | - Jie Ning
- Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.,Shandong Institute of Endocrine and Metabolic Diseases, Jinan, China
| | - Yao Wang
- Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.,Shandong Institute of Endocrine and Metabolic Diseases, Jinan, China
| | - Yan Yan
- Department of Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Zhi-Bin Wang
- Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.,Shandong Institute of Endocrine and Metabolic Diseases, Jinan, China
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23
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Jiang Y, Zheng R, Sang H. Cost-Effectiveness of Adding SGLT2 Inhibitors to Standard Treatment for Heart Failure With Reduced Ejection Fraction Patients in China. Front Pharmacol 2021; 12:733681. [PMID: 34858172 PMCID: PMC8631914 DOI: 10.3389/fphar.2021.733681] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 10/20/2021] [Indexed: 12/11/2022] Open
Abstract
Objective: To evaluate the economics and effectiveness of adding dapagliflozin or empagliflozin to the standard treatment for heart failure (HF) for patients with reduced ejection fraction (HFrEF) in China. Methods: A Markov model was developed to project the clinical and economic outcomes of adding dapagliflozin or empagliflozin to the standard treatment for 66-year-old patients with HFrEF. A cost-utility analysis was performed based mostly on data from the empagliflozin outcome trial in patients with chronic heart failure and a reduced ejection fraction (EMPEROR-Reduced) study and the dapagliflozin and prevention of adverse outcomes in heart failure (DAPA-HF) trial. The primary outcomes were measured via total and incremental costs and quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER). Results: In China, compared to the standard treatment, although adding dapagliflozin to the standard treatment in the treatment of HFrEF was more expensive ($4,870.68 vs. $3,596.25), it was more cost-effective (3.87 QALYs vs. 3.64 QALYs), resulting in an ICER of $5,541.00 per QALY. Similarly, adding empagliflozin was more expensive ($5,021.93 vs. $4,118.86) but more cost-effective (3.66 QALYs vs. 3.53 QALYs), resulting in an ICER of $6,946.69 per QALY. A sensitivity analysis demonstrated the robustness of the model in identifying cardiovascular death as a significant driver of cost-effectiveness. A probabilistic sensitivity analysis indicated that when the willingness-to-pay was $11,008.07 per QALY, the probability of the addition of dapagliflozin or empagliflozin being cost-effective was 70.5 and 55.2%, respectively. A scenario analysis showed that the cost of hospitalization, diabetes status, and time horizon had a greater impact on ICER. Conclusion: Compared with standard treatments with or without empagliflozin, adding dapagliflozin to the standard treatment in the treatment of HFrEF in China was extremely cost-effective.
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Affiliation(s)
- Yaohui Jiang
- Department Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Rujie Zheng
- Department Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Haiqiang Sang
- Department Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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24
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Abstract
Alterations of endothelial function, inflammatory activation, and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway are involved in the pathophysiology of heart failure. Metabolic alterations have been studied in the myocardium of heart failure (HF) patients; alterations in ketone body and amino acid/protein metabolism have been described in patients affected by HF, as well as mitochondrial dysfunction and other modified metabolic signaling. However, their possible contributions toward cardiac function impairment in HF patients are not completely known. Recently, sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have emerged as a new class of drugs designed to treat patients with type 2 diabetes (T2D), but have also been shown to be protective against HF-related events and CV mortality. To date, the protective cardiovascular effects of these drugs in patients with and without T2D are not completely understood and several mechanisms have been proposed. In this review, we discuss on vascular and metabolic effects of SGLT2i and GLP-1 in HF patients.
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25
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Stoicescu M, Calniceanu H, Țig I, Nemeth S, Tent A, Popa A, Brisc C, Ignat-Romanul I. Significant aspects and correlation between glycemic control and generalized chronic periodontitis in type 2 diabetes mellitus patients. Exp Ther Med 2021; 22:671. [PMID: 33986836 DOI: 10.3892/etm.2021.10103] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 03/12/2021] [Indexed: 12/17/2022] Open
Abstract
The purpose of this research was to assess the correlation between glycemic control and clinical periodontal characteristics in type 2 diabetics with generalized chronic periodontitis. A total of 182 patients with type 2 diabetes mellitus and generalized chronic periodontitis were included in our study. The clinical examination included full-mouth plaque accumulation, bleeding on probing (BoP), probing depth (PD), presence of suppuration (SUP), clinical attachment level (CAL) and number of remaining teeth. Blood analyses were conducted for glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG). The correlation between the extent of periodontitis, defined as the percentage of PD and CAL sites ≥5 mm, and glycemic control was also analyzed. In addition, clinical parameters were compared between two (<7 and ≥7%) glycemic subsets. The frequency of uncontrolled diabetic subjects (HbA1c ≥7%) was higher than that of the well-controlled subjects (HbA1c <7%), 57.15 vs. 42.85%. Among the clinical parameters evaluated, mean full-mouth plaque accumulation was significantly higher among patients without glucose control (74.2±25.2 vs. 62.5±28.7%, P<0.01), as well as mean PD (3.78±0.9 vs. 3.42±0.8 mm, P<0.01) and mean CAL (4.5±1.2 vs. 4.1±1.2 mm, P=0.02). The sites with PD ≥5 mm were statistically more prevalent among patients with HbA1c ≥7% compared with patients with HbA1c <7% (27.8±6.2 vs. 23.4±5.8%, P<0.01). The mean number of remaining teeth was statistically significantly lower in patients with HbA1c ≥7% compared with patients with HbA1c <7% (18.5±3.2 vs. 20.4±4.1, P<0.01). In conclusion, the severity and extension of generalized chronic periodontitis was higher in type 2 diabetes mellitus patients with poor glucose control compared with those with good glucose control.
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Affiliation(s)
- Manuela Stoicescu
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Horea Calniceanu
- Department of Periodontology, 'Victor Babes' University of Medicine and Pharmacy of Timisoara, 300041 Timisoara, Romania
| | - Ioan Țig
- Department of Dental Medicine, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Sebastian Nemeth
- Pharmacy Department, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
| | - Adriana Tent
- Department of Dental Medicine, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Adelina Popa
- Department of Orthodontics, 'Victor Babes' University of Medicine and Pharmacy of Timisoara, 300041 Timisoara, Romania
| | - Ciprian Brisc
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Ioana Ignat-Romanul
- Department of Dental Medicine, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
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26
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Ceauşu Z, Socea B, Costache M, Predescu D, Şerban D, Smarandache CG, Pacu I, Alexandru HH, Daviţoiu AM, Jacotă-Alexe F, Cîrstoveanu C, Dimitriu MC, Pleş L, Ceauşu M. Fibroblast involvement in cardiac remodeling and repair under ischemic conditions. Exp Ther Med 2021; 21:269. [PMID: 33603876 PMCID: PMC7851673 DOI: 10.3892/etm.2021.9700] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 11/24/2020] [Indexed: 12/20/2022] Open
Abstract
Cardiac fibroblasts play a main role in the physiological turnover of the extracellular matrix, as well as its pathological remodeling. A study was performed on a batch of 23 cases who died of various cardiac complications secondary to scarring myocardial infarctions. The aim of the study was to assess the fibroblast involvement in cardiac repair under ischemic conditions after myocardial infarction. Tissue myocardial samples from the left ventricle were taken from these cases for microscopy examination, in order to investigate the type and degree of fibrosis as well as the presence of cardiac interstitial fibroblasts. Multiple series of histological sections were also performed and examined, along with immunohistochemical analysis. The fibroblasts were diffusely distributed in the interstitium among the residual cardiomyocytes, showing variable expression of vimentin and smooth muscle actin. During cardiac remodeling, there was a successive interstitial deposition, first of reticulin fibers and then of collagen fibers, leading to interstitial fibrosis and myocardial replacement. There was a correlation between vimentin and smooth muscle actin expression and collagen deposition. Fibrosis with cardiac remodeling is based on maintaining proliferation capacity of the fibroblast and its capacity of protein synthesis in the extracellular matrix. Under hypoxic ischemic conditions, followed by myocardial infarction, the fibroblast switches phenotype and transdifferentiate into myofibroblast, contributing to the healing by secreting extracellular matrix proteins and collagen deposition, with subsequent cardiac remodeling and regulation of the micro-environment metabolism.
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Affiliation(s)
- Zenaida Ceauşu
- Department of Pathology, ‘Sf. Pantelimon’ Emergency Hospital, 021659 Bucharest, Romania
| | - Bogdan Socea
- Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Surgery, ‘Sf. Pantelimon’ Emergency Hospital, 021659 Bucharest, Romania
- Correspondence to: Dr Bogdan Socea, Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
| | - Mariana Costache
- Department of Pathology, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Pathology, University Emergency Hospital, 050098 Bucharest, Romania
| | - Dragoş Predescu
- Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Surgery, ‘Sf. Maria’ Hospital, 011172 Bucharest, Romania
| | - Dragoş Şerban
- Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Surgery, University Emergency Hospital, 050098 Bucharest, Romania
| | - Cătălin G. Smarandache
- Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Surgery, University Emergency Hospital, 050098 Bucharest, Romania
| | - Irina Pacu
- Department of Obstetrics and Gynecology, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Obstetrics and Gynecology, ‘Sf. Pantelimon’ Emergency Hospital, 021659 Bucharest, Romania
| | - Haradja Horaţiu Alexandru
- Department of Obstetrics and Gynecology, ‘Sf. Pantelimon’ Emergency Hospital, 021659 Bucharest, Romania
- PhD Fellowship, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Ana Maria Daviţoiu
- Department of Pediatrics, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Pediatrics, ‘Doctor Victor Gomoiu’ Emergency Children Clinical Hospital, 022102 Bucharest, Romania
| | - Florentina Jacotă-Alexe
- Department of Obstetrics and Gynecology, ‘Sf. Pantelimon’ Emergency Hospital, 021659 Bucharest, Romania
| | - Cătălin Cîrstoveanu
- Department of Pediatrics, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Pediatrics, ‘Maria Sklodowska Curie’ Emergency Children Clinical Hospital, 041451 Bucharest, Romania
| | - Mihai C.T. Dimitriu
- Department of Obstetrics and Gynecology, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Obstetrics and Gynecology, ‘Sf. Pantelimon’ Emergency Hospital, 021659 Bucharest, Romania
| | - Liana Pleş
- Department of Obstetrics and Gynecology, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Obstetrics and Gynecology, ‘Sf. Ioan’ Hospital-Bucur, 040294 Bucharest, Romania
| | - Mihai Ceauşu
- Department of Pathology, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
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27
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Cui J, Liu Y, Li Y, Xu F, Liu Y. Type 2 Diabetes and Myocardial Infarction: Recent Clinical Evidence and Perspective. Front Cardiovasc Med 2021; 8:644189. [PMID: 33718461 PMCID: PMC7943438 DOI: 10.3389/fcvm.2021.644189] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Accepted: 01/19/2021] [Indexed: 12/12/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) and its complications are seriously affecting public health worldwide. Myocardial infarction (MI) is the primary cause of death in patients with T2DM. T2DM patients without a history of coronary artery disease (CAD) have the same risk of major coronary events as those with CAD; T2DM patients with a history of MI have >40% risk of recurrence of MI. Thus, CAD in patients with T2DM needs to be treated actively to reduce the risk of MI. The cardiology community focused on the role of T2DM in the development of CAD and on the related issues of T2DM and MI with respect to comorbidities, prognosis, drug therapy, and heredity. In this mini review, the latest progress of clinical evidence-based research between T2DM and MI in recent years was reviewed, and the possible research directions in this field were considered and prospected.
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Affiliation(s)
- Jing Cui
- Cardiovascular Centre of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,National Clinical Research Centre for Chinese Medicine Cardiology, Beijing, China
| | - Yanfei Liu
- Institute of Clinical Pharmacology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Yiwen Li
- Cardiovascular Centre of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,National Clinical Research Centre for Chinese Medicine Cardiology, Beijing, China.,China Center for Evidence-Based Medicine of Chinese Medicine, Beijing, China
| | - Fengqin Xu
- National Clinical Research Centre for Chinese Medicine Cardiology, Beijing, China.,China Center for Evidence-Based Medicine of Chinese Medicine, Beijing, China
| | - Yue Liu
- Cardiovascular Centre of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,National Clinical Research Centre for Chinese Medicine Cardiology, Beijing, China.,China Center for Evidence-Based Medicine of Chinese Medicine, Beijing, China
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28
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Wang C, Ye D, Xie Z, Huang X, Wang Z, Shangguan H, Zhu W, Wang S. Assessment of Cardiovascular Risk Factors and Their Interactions in the Risk of Coronary Heart Disease in Patients with Type 2 Diabetes with Different Weight Levels, 2013-2018. Diabetes Metab Syndr Obes 2021; 14:4253-4262. [PMID: 34703258 PMCID: PMC8523514 DOI: 10.2147/dmso.s335017] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 10/07/2021] [Indexed: 12/29/2022] Open
Abstract
PURPOSE In addition to hyperglycemia and hyperlipidemia, obesity and hypertension are important cardiovascular risk factors for coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM). This study aims to explore the interaction of these risk factors. PATIENTS AND METHODS Data of hospitalized patients with T2DM from 2013 to 2018 were collected. A multivariate logistic regression model was established. Patients with normal weight and blood pressure were recruited as controls. The interaction on the risk of CHD was evaluated by relative excess risk due to interaction (RERI). RESULTS Among the 30,693 patients with T2DM, 7202 (23.5%) had CHD. In the low weight group, the prevalence of CHD in patients with hypertension was nearly four times higher than that in patients without hypertension (42.7% vs 11.3%, P < 0.01). The OR value of hypertension alone on CHD increased from 1.29 (95% CI 1.06-1.56) in the body mass index (BMI) 30.0-34.9 kg/m2 group to 1.35 (95% CI 1.11-1.62) in the BMI ≤ 18.5 kg/m2 group. Additive interaction was observed between hypertension and BMI in CHD risk, especially in the low weight group (RERI:2.2, 95% CI 0.9-3.5). BMI and CHD risk showed a smile curve relationship. The attributive proportion in the low weight group was higher than that in the severe obesity group, that is, 0.52 (95% CI 0.35-0.69) vs 0.18 (95% CI -0.59 to 0.95). CONCLUSION Maintaining normal weight and avoiding low weight are particularly important for patients with co-occurring diabetes and hypertension to prevent the risk of CHD.
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Affiliation(s)
- Chenchen Wang
- Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, People’s Republic of China
- School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China
| | - Demei Ye
- Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, People’s Republic of China
| | - Zuoling Xie
- Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, People’s Republic of China
- School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China
| | - Xi Huang
- Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, People’s Republic of China
| | - Zheng Wang
- School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China
| | - Haiyan Shangguan
- School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China
- Nanjing Central Hospital, Nanjing, 210008, People’s Republic of China
| | - Wenwen Zhu
- School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China
| | - Shaohua Wang
- Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, People’s Republic of China
- Correspondence: Shaohua Wang Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, People’s Republic of ChinaTel +86 25 83262810Fax +86 25 83285132 Email
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29
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Boda D. 2nd Special Issue: Tackling key immunological and immuno-dermatological pathways and their link to treatment options. Exp Ther Med 2020; 20:2339-2343. [PMID: 32793306 PMCID: PMC7418504 DOI: 10.3892/etm.2020.8977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 07/07/2020] [Indexed: 11/12/2022] Open
Affiliation(s)
- Daniel Boda
- Research Laboratory, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.,Department of Dermatology, 'Prof. N. Paulescu' National Institute of Diabetes, Nutrition and Metabolic Diseases, 79811 Bucharest, Romania
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