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Rezaee M, Nasehi MM, Aminzade Z, Karami H, Vahdani AM, Daroudi R, Effatpanah M, Ghamkhar L, Heidari-Foroozan M, Arab M, Shahali Z, Mehrizi R. Prescription patterns and the cost of antihyperglycemic drugs in patients with diabetes mellitus in Iran from 2014 to 2019. Diabetes Res Clin Pract 2025; 223:112078. [PMID: 40096947 DOI: 10.1016/j.diabres.2025.112078] [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: 10/15/2024] [Revised: 02/26/2025] [Accepted: 03/03/2025] [Indexed: 03/19/2025]
Abstract
INTRODUCTION Diabetes mellitus (DM) is characterized by high blood glucose levels and abnormalities in metabolism. In 2021, 15.14% of adult Iranians had DM. The purpose of this study is to provide policymakers with actionable insights to enhance resource allocation and improve diabetes care by evaluating the prescription patterns and costs of antidiabetic medications in Iran from 2014 to 2019 in 2.5 million patients. METHODS This descriptive-analytical study used data from Iran's Health Insurance prescriptions database, analyzing approximately 2.5 million diabetic patients from 2014 to 2019. Data included drug types, frequencies, costs, and patient demographics. RESULTS The analysis covered 20,233,608 prescriptions. Biguanides, sulfonylureas, and Insulin were the most commonly prescribed medications. Moreover, the 40-64 age group had the highest cost. Prescription patterns varied by age, with insulin in younger patients and Metformin in older ones. General practitioners, internal medicine specialists, and endocrinologists were the primary prescribers of anti-diabetic medications. Insulin Aspart incurred the highest costs, followed by Insulin glargine and metformin. The cost of females' antidiabetic medications was 1.66 times higher than those of males. CONCLUSION Insulin was the primary cost driver for antihyperglycemic medications. These cost disparities and variations in prescription patterns underscore the need for targeted interventions to improve diabetes care and manage resources effectively.
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Affiliation(s)
- Mehdi Rezaee
- Department of Orthopedics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohamad Mehdi Nasehi
- Pediatric Neurology Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Pediatric Neurology Department, Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Aminzade
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Endometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Karami
- National Center for Health Insurance Research, Tehran, Iran
| | - Amir Mohammad Vahdani
- Image Guided Surgery Lab, Research Center for Biomedical Technologies and Robotics, Advanced Medical Technologies and Equipment Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Rajabali Daroudi
- Department of Health Management, Policy and Economics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Effatpanah
- Pediatric Department, School of Medicine, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Leila Ghamkhar
- National Center for Health Insurance Research, Tehran, Iran
| | - Mahsa Heidari-Foroozan
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Arab
- National Center for Health Insurance Research, Tehran, Iran
| | - Zahra Shahali
- National Center for Health Insurance Research, Tehran, Iran
| | - Reza Mehrizi
- National Center for Health Insurance Research, Tehran, Iran; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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Lee SE, Park JH, Kim D, Lee HA, Kang YS, Yoon YS, Jeong YJ, Choi HS, Kim KA. Add-On Treatment with Gliclazide for Cancer Patients with Type 2 Diabetes Undergoing Cyclic Glucocorticoid-Containing Chemotherapy. Biomedicines 2025; 13:1101. [PMID: 40426928 PMCID: PMC12109127 DOI: 10.3390/biomedicines13051101] [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] [Subscribe] [Scholar Register] [Received: 04/03/2025] [Revised: 04/26/2025] [Accepted: 04/29/2025] [Indexed: 05/29/2025] Open
Abstract
Aims: Despite its high prevalence, studies on glucocorticoid-induced hyperglycemia are lacking. We examined the glucose profiles of patients with type 2 diabetes undergoing dexamethasone-containing chemotherapy using continuous glucose monitoring (CGM). We also investigated the effects of gliclazide on the management of hyperglycemia in these patients. Materials and Methods: Seventeen patients with type 2 diabetes who received cyclic chemotherapy with dexamethasone were enrolled in this study. During the first cycle, iPro2, a blinded CGM device, was applied for 7 days. If a patient's CGM data exhibited an increase of 20% or more in the mean glucose level after dexamethasone administration, they received the second cycle, unless they had already received sulfonylurea or their chemotherapy regimen had changed. During the second cycle, the patients were treated with gliclazide as an add-on to their routine diabetic medication. Results: Dexamethasone treatment significantly increased glucose levels, especially in patients with a longer diabetes duration (8.4 years vs. 1.2 years, p = 0.009). For the nine patients who proceeded to the second cycle, gliclazide treatment significantly ameliorated hyperglycemia. Time in range increased from 33.11% to 45.22% (p = 0.020), and time above range significantly decreased from 66.89% to 52.78% (p = 0.003). The glucose management indicators were 9.52% and 8.40% for pre- and post-gliclazide treatment, respectively. One patient visited the emergency department because of symptomatic hypoglycemia. Conclusions: Chemotherapy regimens containing dexamethasone result in high blood glucose levels even after the last dexamethasone dose in patients with pre-existing diabetes. Adding gliclazide could be beneficial in managing hyperglycemia during dexamethasone-containing chemotherapy.
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Affiliation(s)
- Seung Eun Lee
- Internal Medicine, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea; (S.E.L.); (D.K.); (H.-A.L.); (Y.S.K.); (Y.S.Y.); (Y.J.J.); (H.S.C.)
| | - Ju-Hyun Park
- Department of Statistics, Dongguk University, Seoul 04620, Republic of Korea;
| | - Dalyong Kim
- Internal Medicine, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea; (S.E.L.); (D.K.); (H.-A.L.); (Y.S.K.); (Y.S.Y.); (Y.J.J.); (H.S.C.)
| | - Hyun-A Lee
- Internal Medicine, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea; (S.E.L.); (D.K.); (H.-A.L.); (Y.S.K.); (Y.S.Y.); (Y.J.J.); (H.S.C.)
| | - Yun Seong Kang
- Internal Medicine, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea; (S.E.L.); (D.K.); (H.-A.L.); (Y.S.K.); (Y.S.Y.); (Y.J.J.); (H.S.C.)
| | - Young Soon Yoon
- Internal Medicine, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea; (S.E.L.); (D.K.); (H.-A.L.); (Y.S.K.); (Y.S.Y.); (Y.J.J.); (H.S.C.)
| | - Yun Jeong Jeong
- Internal Medicine, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea; (S.E.L.); (D.K.); (H.-A.L.); (Y.S.K.); (Y.S.Y.); (Y.J.J.); (H.S.C.)
| | - Han Seok Choi
- Internal Medicine, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea; (S.E.L.); (D.K.); (H.-A.L.); (Y.S.K.); (Y.S.Y.); (Y.J.J.); (H.S.C.)
| | - Kyoung-Ah Kim
- Internal Medicine, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea; (S.E.L.); (D.K.); (H.-A.L.); (Y.S.K.); (Y.S.Y.); (Y.J.J.); (H.S.C.)
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Araki A. Individualized treatment of diabetes mellitus in older adults. Geriatr Gerontol Int 2024; 24:1257-1268. [PMID: 39375857 PMCID: PMC11628902 DOI: 10.1111/ggi.14979] [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: 06/15/2024] [Revised: 08/05/2024] [Accepted: 08/27/2024] [Indexed: 10/09/2024]
Abstract
The population of older adults with diabetes mellitus is growing but heterogeneous. Because geriatric syndromes, comorbidity or multimorbidity, the complexity of glucose dynamics, and socioeconomic conditions are associated with the risk of severe hypoglycemia and mortality, these factors should be considered in individualized diabetes treatment. Because cognitive impairment and frailty have similar etiologies and risk factors, a common strategy can be implemented to address them through optimal glycemic control, management of vascular risk factors, diet, exercise, social participation, and support. To prevent frailty or sarcopenia, optimal energy intake, adequate protein and vitamin intake, and resistance or multi-component exercise are recommended. For hypoglycemic drug therapy, it is important to reduce hypoglycemia, to use sodium glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, taking into account the benefits for cardiovascular disease and the risk of adverse effects, and to simplify treatment to address poor adherence. Glycemic control goals for older adults with diabetes should be set according to three categories, based on cognitive function and activities of daily living, using the Dementia Assessment Sheet for Community-based Integrated Care System 8-items. This categorization can be used to determine treatment strategies for diabetes when combined with the Comprehensive Geriatric Assessment (CGA). Based on the CGA, frailty prevention, treatment simplification, and social participation or services should be implemented for patients in Category II and above. Measures against hypoglycemia and for the prevention of cardiovascular disease and chronic kidney disease should also be promoted. Treatment based on categorization and CGA by multidisciplinary professionals would be an individualized treatment for older adults with diabetes. Geriatr Gerontol Int 2024; 24: 1257-1268.
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Affiliation(s)
- Atsushi Araki
- Department of Diabetes, Metabolism, and EndocrinologyTokyo Metropolitan Institute for Geriatrics and GerontologyTokyoJapan
- Center for Comprehensive Care and Research for PrefrailtyTokyo Metropolitan Institute for Geriatrics and GerontologyTokyoJapan
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Cahyaningsih I, Asiri A, de Vos S, Bos JHJ, Schuiling-Veninga CCM, Taxis K, Denig P. Screening for Hypoglycaemia Risk and Medication Changes in Diabetes Patients Using Pharmacy Dispensing Data. J Clin Med 2024; 13:5855. [PMID: 39407915 PMCID: PMC11477424 DOI: 10.3390/jcm13195855] [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: 08/16/2024] [Revised: 09/07/2024] [Accepted: 09/26/2024] [Indexed: 10/20/2024] Open
Abstract
Background: To improve hypoglycaemia management in primary care, more insight is needed into the opportunities to screen for hypoglycaemia risk and subsequent treatment modification using routinely available data. Our primary aim was to assess the number of diabetes patients with an estimated high risk of hypoglycaemia and describe the treatment changes in these patients using pharmacy dispensing data. Additionally, our aim was to investigate patient characteristics associated with such treatment changes. Methods: A drug utilisation cohort study with a 1-year follow-up using the IADB.nl pharmacy database was conducted. Patients aged 35 years or older who received at least two glucose-lowering medication dispensings in 2019 were included. Hypoglycaemia risk was determined using a validated algorithm based on patient demographics and dispensing data. The hypoglycaemia risk score ranged between 0 and 1. The anniversary method was used to evaluate treatment changes after 1 year. Factors associated with treatment changes were assessed by multinomial logistic regression. Results: Around one-quarter (26.9%) of the 36,628 included patients had a hypoglycaemia score of 0.6 or more. After a 1-year follow-up, the majority of these patients (88.9%) experienced no diabetes treatment changes. De-intensification was observed for 8.8% and intensification for 2.3%. Having a high-risk score, being female, and being younger in age were associated with de-intensification. Conclusions: A substantial number of primary care patients using glucose-lowering medications appear at risk of hypoglycaemia, whereas few of them undergo medication de-intensification. Pharmacy dispensing data can be helpful in screening for diabetes patients in whom a review of treatment is indicated.
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Affiliation(s)
- Indriastuti Cahyaningsih
- Department of PharmacoTherapy, -Epidemiology, and -Economics, University of Groningen, 9713 AV Groningen, The Netherlands; (I.C.); (A.A.); (J.H.J.B.); (C.C.M.S.-V.); (K.T.)
- Department of Pharmacist Professional Education, Faculty of Medicine and Health Sciences, Universitas Muhammadiyah Yogyakarta, Yogyakarta 55183, Indonesia
| | - Amal Asiri
- Department of PharmacoTherapy, -Epidemiology, and -Economics, University of Groningen, 9713 AV Groningen, The Netherlands; (I.C.); (A.A.); (J.H.J.B.); (C.C.M.S.-V.); (K.T.)
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Stijn de Vos
- Department of PharmacoTherapy, -Epidemiology, and -Economics, University of Groningen, 9713 AV Groningen, The Netherlands; (I.C.); (A.A.); (J.H.J.B.); (C.C.M.S.-V.); (K.T.)
| | - Jens H. J. Bos
- Department of PharmacoTherapy, -Epidemiology, and -Economics, University of Groningen, 9713 AV Groningen, The Netherlands; (I.C.); (A.A.); (J.H.J.B.); (C.C.M.S.-V.); (K.T.)
| | - Catharina C. M. Schuiling-Veninga
- Department of PharmacoTherapy, -Epidemiology, and -Economics, University of Groningen, 9713 AV Groningen, The Netherlands; (I.C.); (A.A.); (J.H.J.B.); (C.C.M.S.-V.); (K.T.)
| | - Katja Taxis
- Department of PharmacoTherapy, -Epidemiology, and -Economics, University of Groningen, 9713 AV Groningen, The Netherlands; (I.C.); (A.A.); (J.H.J.B.); (C.C.M.S.-V.); (K.T.)
| | - Petra Denig
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, 9713 AV Groningen, The Netherlands
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Baccetti F, Crisafulli C, Andreozzi F, Mannino GC, Nicolucci A, Michelli A, Miranda C, Candido R, Di Bartolo P, Di Cianni G, Russo GT, Mannino D. Profiles of sulfonylurea use in Diabetes Mellitus type 2: an analysis of clinical practice over the last 10 years. Diabetes Res Clin Pract 2024; 214:111781. [PMID: 39002933 DOI: 10.1016/j.diabres.2024.111781] [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: 03/07/2024] [Revised: 06/17/2024] [Accepted: 07/08/2024] [Indexed: 07/15/2024]
Abstract
AIMS Describing the evolution over time in the use of sulfonylureas (SUs) and the characteristics of patients at first prescription and at interruption of treatment with SUs. METHODS Retrospective evaluation of data from the Italian Association of Diabetologists (AMD) Annals registry (2010-2020), about T2D patients who started treatment with SUs. The longitudinal probability of remaining on SUs was estimated by Kaplan Meier survival curves. RESULTS SU prescription decreased from 30.7 % (2010) to 12.9 % (2020). Patients started on SU were 68.2 ± 11.2 years old, mostly males (55.5 %), with diabetes duration = 10.1 ± 8.3 years, BMI = 29.7 ± 5.5 kg/m2, and HbA1c = 8.3 ± 1.7 % [67 mmol/mol]. After one year, the probability of staying on SU was 85.4 %, 75.9 % after two years, 68.2 % after 3 years, 56.6 % after 5 years. Patients who discontinued SUs had higher BMI and HbA1c, were younger, more often males and treated with insulin. Over time, the percentage of subjects switched to metformin, DPP4i, SGLT2i, and GLP1RA increased, whereas use of glinides, glitazones, acarbose and insulin declined. CONCLUSIONS These data suggest a consensus, slowly, but increasingly aligning with the current National indications of dismissing SUs for the treatment of T2D. The new drugs for diabetes should represent a preferable choice in all patients who do not have specific contraindications.
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Affiliation(s)
| | | | - Francesco Andreozzi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy; Research Centre for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Gaia Chiara Mannino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy.
| | - Antonio Nicolucci
- CORESEARCH-Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy
| | - Andrea Michelli
- Department of Internal Medicine, SC Diabetes and Center for Treatment of Diabetic Foot, Monfalcone, Gorizia, Italy
| | - Cesare Miranda
- Clinic of Endocrinology and Metabolic Diseases, Pordenone Hospital, Pordenone, Italy
| | - Riccardo Candido
- Diabetes Center, ASUGI University Hospital Giuliano Isontina, Trieste, Italy
| | - Paolo Di Bartolo
- Diabetes Unit, Local Healthcare Authority of Romagna, Ravenna, Italy
| | - Graziano Di Cianni
- ASL North-West Tuscany, Diabetes and Metabolic Diseases, Livorno Hospital, Livorno, Italy
| | - Giuseppina Tiziana Russo
- Department of Clinical and Experimental Medicine, University Hospital G. Martino, Messina, Italy
| | - Domenico Mannino
- Section of Endocrinology and Diabetes, Bianchi Melacrino Morelli Hospital, Reggio Calabria, Italy; AMD Annals Initiative, AMD Foundation, Rome, Italy
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Getahun BM, Gebeyehu MA, Getahun AM, Kassie YG. Severe hypoglycemia in a diabetic patient with pituitary apoplexy: a case report. J Med Case Rep 2024; 18:349. [PMID: 39085948 PMCID: PMC11293190 DOI: 10.1186/s13256-024-04642-9] [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: 04/04/2024] [Accepted: 06/15/2024] [Indexed: 08/02/2024] Open
Abstract
INTRODUCTION Hypoglycemia is a common occurrence in diabetic patients. But unlike non diabetic patients, its causes are frequently related to drugs they are receiving to control blood glucose. But this may not always be the case. Here we report a type 2 diabetic patient with severe hypoglycemia owing to acute hypopituitarism secondary to pituitary apoplexy. CASE PRESENTATION A 45 year old male diabetic patient from Ethiopia taking 2 mg of oral glimepiride daily who presented with change in mentation of 30 minutes and blood glucose recording of 38 mg/dl upon arrival to the emergency room. Brain magnetic resonance imaging showed pituitary macroadenoma with hemorrhage suggestive of pituitary apoplexy. Blood work up showed low adrenocorticotropic hormone, cortisol, and serum sodium levels. Subsequently transsphenoidal hypophysectomy was done. CONCLUSION The occurrence of hypoglycemia in a diabetic patient taking sulphonylurea monotherapy is common. But when it is severe enough to cause altered mentation, patients should be approached differently. In the presence of clinical clues suggesting cortisol deficiency, hypopituitarism can be a possible cause.
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Conroy LJ, McCann A, Zhang N, de Gaetano M. The role of nanosystems in the delivery of glucose-lowering drugs for the preemption and treatment of diabetes-associated atherosclerosis. Am J Physiol Cell Physiol 2024; 326:C1398-C1409. [PMID: 38525540 DOI: 10.1152/ajpcell.00695.2023] [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: 12/14/2023] [Revised: 03/19/2024] [Accepted: 03/19/2024] [Indexed: 03/26/2024]
Abstract
Diabetes is one of the most prevalent diseases worldwide. In recent decades, type-2 diabetes has become increasingly common, particularly in younger individuals. Diabetes leads to many vascular complications, including atherosclerosis. Atherosclerosis is a cardiovascular disease characterized by lipid-rich plaques within the vasculature. Plaques develop over time, restricting blood flow, and can, therefore, be the underlying cause of major adverse cardiovascular events, including myocardial infarction and stroke. Diabetes and atherosclerosis are intrinsically linked. Diabetes is a metabolic syndrome that accelerates atherosclerosis and increases the risk of developing other comorbidities, such as diabetes-associated atherosclerosis (DAA). Gold standard antidiabetic medications focus on attenuating hyperglycemia. Though recent evidence suggests that glucose-lowering drugs may have broader applications, beyond diabetes management. This review mainly evaluates the role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as liraglutide and semaglutide in DAA. These drugs mimic gut hormones (incretins), which inhibit glucagon secretion while stimulating insulin secretion, thus improving insulin sensitivity. This facilitates delayed gastric emptying and increased patient satiety; hence, they are also indicated for the treatment of obesity. GLP-1 RAs have significant cardioprotective effects, including decreasing low-density lipoprotein (LDL) cholesterol and triglycerides levels. Liraglutide and semaglutide have specifically been shown to decrease cardiovascular risk. Liraglutide has displayed a myriad of antiatherosclerotic properties, with the potential to induce plaque regression. This review aims to address how glucose-lowering medications can be applied to treat diseases other than diabetes. We specifically focus on how nanomedicines can be used for the site-specific delivery of antidiabetic medicines for the treatment of diabetes-associated atherosclerosis.
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Affiliation(s)
- Luke James Conroy
- Diabetes Complications Research Centre, Conway Institute & School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
| | - Alyssa McCann
- School of Mechanical and Materials Engineering, University College Dublin, Dublin, Ireland
| | - Nan Zhang
- School of Mechanical and Materials Engineering, University College Dublin, Dublin, Ireland
| | - Monica de Gaetano
- Diabetes Complications Research Centre, Conway Institute & School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
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Mazraesefidi M, Mahmoodi M, Hajizadeh M. Effects of silibinin on apoptosis and insulin secretion in rat RINm5F pancreatic β-cells. Biotech Histochem 2023; 98:201-209. [PMID: 36762428 DOI: 10.1080/10520295.2022.2154840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023] Open
Abstract
We investigated whether silibinin, a flavonoid, might be useful for treating diabetes mellitus by treating five groups of rat RINm5F β-insulinemia cells as follows: control streptozotocin (STZ) group administered citrate buffer and dimethyl sulfoxide; STZ group administered 20 mM STZ; silibinin group administered 50 µM silibinin; pre-silibinin group administered 50 µM silibinin 5 h before administering 20 mM STZ; simultaneous group administered 50 µM silibinin at the same time as 20 mM STZ. For all groups, MTT assay and flow cytometry were used to evaluate cell viability and necrosis, respectively. Glucose-stimulated insulin secretion (GSIS) and insulin cell content were determined using enzyme-linked immunosorbent assay. Also, expression of genes, pancreatic and duodenal homeobox 1 (pdx1), neuronal differentiation 1 (neurod1), v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog A (mafa), glucose transporter 2 (glut2)) was determined using the real-time polymerase chain reaction. We found that silibinin improved the viability of RINm5F cells and increased GSIS and cellular insulin under glucotoxic conditions. Silibinin increased the expression of neurod1, mafa and glut2, but reduced pdx1 expression. Our findings suggest that silibinin might increase glucose sensitivity and insulin synthesis under glucotoxic conditions, which could be useful for diabetes treatment.
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Affiliation(s)
- Maryam Mazraesefidi
- Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Mehdi Mahmoodi
- Department of Clinical Biochemistry, Afzalipoor Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammadreza Hajizadeh
- Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
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DeMarsilis A, Reddy N, Boutari C, Filippaios A, Sternthal E, Katsiki N, Mantzoros C. Pharmacotherapy of type 2 diabetes: An update and future directions. Metabolism 2022; 137:155332. [PMID: 36240884 DOI: 10.1016/j.metabol.2022.155332] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 10/07/2022] [Accepted: 10/07/2022] [Indexed: 11/06/2022]
Abstract
Type 2 diabetes (T2D) is a widely prevalent disease with substantial economic and social impact for which multiple conventional and novel pharmacotherapies are currently available; however, the landscape of T2D treatment is constantly changing as new therapies emerge and the understanding of currently available agents deepens. This review aims to provide an updated summary of the pharmacotherapeutic approach to T2D. Each class of agents is presented by mechanism of action, details of administration, side effect profile, cost, and use in certain populations including heart failure, non-alcoholic fatty liver disease, obesity, chronic kidney disease, and older individuals. We also review targets of novel therapeutic T2D agent development. Finally, we outline an up-to-date treatment approach that starts with identification of an individualized goal for glycemic control then selection, initiation, and further intensification of a personalized therapeutic plan for T2D.
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Affiliation(s)
- Antea DeMarsilis
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | - Niyoti Reddy
- Department of Medicine, School of Medicine, Boston University, Boston, USA
| | - Chrysoula Boutari
- Second Propedeutic Department of Internal Medicine, Hippocration Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Andreas Filippaios
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | - Elliot Sternthal
- Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, MA 02115, USA
| | - Niki Katsiki
- Department of Nutritional Sciences and Dietetics, International Hellenic University, Sindos, Greece; School of Medicine, European University Cyprus, Nicosia, Cyprus.
| | - Christos Mantzoros
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA; Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, MA 02115, USA
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Danilov DV, D’yachenko VS, Burmistrov VV, Butov GM. Synthesis and Properties of 1,3-Disubstituted Ureas and Their Isosteric Analogs Containing Polycyclic Fragments: XVI. Synthesis and Properties of 1,1'-(Alkane-1,n-diyl)bis{3-[(3,5-dimethyladamantan-1-yl)methyl]ureas}. RUSSIAN JOURNAL OF ORGANIC CHEMISTRY 2022. [DOI: 10.1134/s107042802211001x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Roeb E, Canbay A, Bantel H, Bojunga J, de Laffolie J, Demir M, Denzer UW, Geier A, Hofmann WP, Hudert C, Karlas T, Krawczyk M, Longerich T, Luedde T, Roden M, Schattenberg J, Sterneck M, Tannapfel A, Lorenz P, Tacke F. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:1346-1421. [PMID: 36100202 DOI: 10.1055/a-1880-2283] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- E Roeb
- Gastroenterologie, Medizinische Klinik II, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - A Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - H Bantel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - J Bojunga
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin., Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - J de Laffolie
- Allgemeinpädiatrie und Neonatologie, Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - M Demir
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
| | - U W Denzer
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Marburg, Deutschland
| | - A Geier
- Medizinische Klinik und Poliklinik II, Schwerpunkt Hepatologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - W P Hofmann
- Gastroenterologie am Bayerischen Platz - Medizinisches Versorgungszentrum, Berlin, Deutschland
| | - C Hudert
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - T Karlas
- Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - M Krawczyk
- Klinik für Innere Medizin II, Gastroent., Hepat., Endokrin., Diabet., Ern.med., Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - T Longerich
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - T Luedde
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - M Roden
- Klinik für Endokrinologie und Diabetologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - J Schattenberg
- I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
| | - M Sterneck
- Klinik für Hepatobiliäre Chirurgie und Transplantationschirurgie, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - A Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - P Lorenz
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - F Tacke
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
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12
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Galindo RJ, Dhatariya K, Gomez-Peralta F, Umpierrez GE. Safety and Efficacy of Inpatient Diabetes Management with Non-insulin Agents: an Overview of International Practices. Curr Diab Rep 2022; 22:237-246. [PMID: 35507117 PMCID: PMC9065239 DOI: 10.1007/s11892-022-01464-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/14/2022] [Indexed: 12/25/2022]
Abstract
PURPOSE OF REVIEW The field of inpatient diabetes has advanced significantly over the last 20 years, leading to the development of personalized treatment approaches. However, outdated guidelines still recommend the use of basal-bolus insulin therapy as the preferred treatment approach, and against the use of non-insulin anti-hyperglycemic agents. RECENT FINDINGS Several observational and prospective randomized controlled studies have demonstrated that oral anti-hyperglycemic agents are widely used in the hospital, including studies of DPP-4 agents and GLP-1 agonists. With advances in the field of inpatient diabetes management, a paradigm shift has occurred, from an approach of recommending "basal-bolus regimens" for all patients to a more precision medicine option for hospitalized non-critically ill patients with type 2 diabetes.
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Affiliation(s)
- Rodolfo J Galindo
- Associate Professor of Medicine, Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, USA.
| | - Ketan Dhatariya
- Consultant Diabetes & Endocrinology / Honorary Professor, Norwich Medical School, Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospitals, NHS Foundation Trust, Norwich, UK
| | | | - Guillermo E Umpierrez
- Professor of Medicine, Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, USA
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13
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Chantzaras A, Yfantopoulos J. Evaluating the Incidence and Risk Factors Associated With Mild and Severe Hypoglycemia in Insulin-Treated Type 2 Diabetes. Value Health Reg Issues 2022; 30:9-17. [PMID: 35033801 DOI: 10.1016/j.vhri.2021.10.005] [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: 04/28/2021] [Revised: 09/10/2021] [Accepted: 10/14/2021] [Indexed: 12/20/2022]
Abstract
OBJECTIVES This study to assess the incidence rates and risk factors of hypoglycemia in a wide real-life sample of patients with insulin-treated type 2 diabetes mellitus. METHODS In a prospective epidemiological study, data from 817 subjects were collected from medical records and via interviews. Over a 3-month period, hypoglycemic episodes were recorded via self-measurement of glucose levels at least twice daily. Cox proportional and negative binomial multivariable models were applied to estimate adjusted and unadjusted hazard ratios and incidence rate ratios of hypoglycemic events. RESULTS Of the 817 patients, 52.9% experienced hypoglycemia, 38.1% had only nonsevere episodes, and 14.8% had at least 1 severe episode. Total events per patient-year were estimated at 13.3 (±24.8), with 11.8 (±21.6) and 1.4 (±4.7) being nonsevere and severe, respectively. History of hypoglycemia and severe hypoglycemia were consistent risk factors of hypoglycemia. Intensification of therapy was associated with higher incidence rates, whereas the effect on the hazard rates was more moderate. Longer duration of insulin therapy and the presence of congestive heart failure were associated with a higher risk of developing and frequency of hypoglycemia. Hypoglycemia awareness was found to independently affect only mild hypoglycemia. CONCLUSIONS Hypoglycemia is a common complication in patients with insulin-treated type 2 diabetes mellitus. The risk factors of developing hypoglycemia are to some extent different from those of the frequency of hypoglycemic episodes. Particular attention is required for patients with recurrent hypoglycemic events and on intensive antidiabetic therapy.
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Affiliation(s)
- Athanasios Chantzaras
- School of Economics and Political Sciences, National and Kapodistrian University of Athens, Athens, Greece
| | - John Yfantopoulos
- School of Economics and Political Sciences, National and Kapodistrian University of Athens, Athens, Greece.
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14
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Loganadan NK, Huri HZ, Vethakkan SR, Hussein Z. Pharmacogenetics of sulfonylurea-induced hypoglycemia in Type 2 diabetes patients: the SUCLINGEN study. Pharmacogenomics 2021; 22:1057-1068. [PMID: 34665019 DOI: 10.2217/pgs-2021-0059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: This study investigated the incidence of sulfonylurea-induced hypoglycemia and its predictors in Type 2 diabetes (T2D) patients. Patients & methods: In this prospective, observational study, T2D patients on maximal sulfonylurea-metformin therapy >1 year were enrolled. Hypoglycemia was defined as having symptoms or a blood glucose level <3.9 mmol/l. Results: Of the 401 patients, 120 (29.9%) developed sulfonylurea-induced hypoglycemia during the 12-month follow-up. The ABCC8 rs757110, KCNJ11 rs5219, CDKAL1 rs7756992 and KCNQ1 rs2237892 gene polymorphisms were not associated with sulfonylurea-induced hypoglycemia (p > 0.05). Prior history of hypoglycemia admission (odds ratio = 16.44; 95% CI: 1.74-154.33, p = 0.014) independently predicted its risk. Conclusion: Sulfonylurea-treated T2D patients who experienced severe hypoglycemia are at increased risk of future hypoglycemia episodes.
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Affiliation(s)
- Navin Kumar Loganadan
- Department of Pharmacy, Putrajaya Hospital, Precinct 7, Putrajaya, 62250, Malaysia.,Faculty of Pharmacy, University of Malaya, Kuala Lumpur, 50603, Malaysia
| | - Hasniza Zaman Huri
- Faculty of Pharmacy, University of Malaya, Kuala Lumpur, 50603, Malaysia.,Clinical Investigation Centre, 5th Floor, East Tower, University of Malaya Medical Centre, Lembah Pantai, 59100, Kuala Lumpur, Malaysia
| | - Shireene Ratna Vethakkan
- Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia
| | - Zanariah Hussein
- Department of Medicine, Putrajaya Hospital, Precinct 7, Putrajaya, 62250, Malaysia
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15
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Au NH, Ratzki-Leewing A, Zou G, Ryan BL, Webster-Bogaert S, Reichert SM, Brown JB, Harris SB. Real-World Incidence and Risk Factors for Daytime and Nocturnal Non-Severe Hypoglycemia in Adults With Type 2 Diabetes Mellitus on Insulin and/or Secretagogues (InHypo-DM Study, Canada). Can J Diabetes 2021; 46:196-203.e2. [DOI: 10.1016/j.jcjd.2021.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 09/10/2021] [Accepted: 09/14/2021] [Indexed: 10/20/2022]
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16
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Lipscombe L, Butalia S, Dasgupta K, Eurich DT, MacCallum L, Shah BR, Simpson S, Senior PA. Pharmacologic Glycemic Management of Type 2 Diabetes in Adults: 2020 Update. Can J Diabetes 2021; 44:575-591. [PMID: 32972640 DOI: 10.1016/j.jcjd.2020.08.001] [Citation(s) in RCA: 100] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Lorraine Lipscombe
- Division of Endocrinology, Department of Medicine, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Sonia Butalia
- Division of Endocrinology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Kaberi Dasgupta
- Divisions of Internal Medicine, Clinical Epidemiology, and Endocrinology and Metabolism, Department of Medicine; Centre for Outcomes Research and Evaluation, Research Institute, McGill University Health Centre, Montreal, Quebec, Canada
| | - Dean T Eurich
- School of Public Health, University of Alberta, Edmonton, Alberta, Canada
| | - Lori MacCallum
- Banting & Best Diabetes Centre, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
| | - Baiju R Shah
- Division of Endocrinology and Metabolism, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Medicine and Institute for Health Policy Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
| | - Scot Simpson
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - Peter A Senior
- Division of Endocrinology and Metabolism, University of Alberta, Edmonton, Alberta, Canada
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Al-Saleh Y, Sabico S, Al-Furqani A, Jayyousi A, Alromaihi D, Ba-Essa E, Alawadi F, Alkaabi J, Hassanein M, Al-Sifri S, Saleh S, Alessa T, Al-Daghri NM. Sulfonylureas in the Current Practice of Type 2 Diabetes Management: Are They All the Same? Consensus from the Gulf Cooperation Council (GCC) Countries Advisory Board on Sulfonylureas. Diabetes Ther 2021; 12:2115-2132. [PMID: 33983614 PMCID: PMC8342668 DOI: 10.1007/s13300-021-01059-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 04/09/2021] [Indexed: 12/22/2022] Open
Abstract
Since their inception in the commercial market in the mid-twentieth century, sulfonylureas (SUs) have remained a therapeutic option in the management of type 2 diabetes (T2D). Despite their established glucose-lowering effects, there is no consensus among global experts and modern guidelines regarding the priority of SUs in relation to other therapeutic options, given the lack of evidence that SUs are associated with a low risk of macrovascular events and excess mortality. However, findings from recent trials and real-time observations have resolved this contentious issue somewhat, albeit to varying degrees. The present consensus discusses the role of SUs in contemporary diabetes management in the Gulf Cooperation Council (GCC) countries. Regional experts from these countries gathered virtually to formulate a consensus following presentations of topics relevant to SU therapy with an emphasis on gliclazide, including long-term efficacy, cost, end-organ benefits, and side effects, based on up-to-date evidence. The present narrative review reflects the conclusions of this assembly and provides a platform upon which future guidelines for the use of SUs in the GCC can be tailored.
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Affiliation(s)
- Yousef Al-Saleh
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, 22490, Saudi Arabia.
- King Abdullah International Medical Research Center, Riyadh, 11481, Saudi Arabia.
- Department of Medicine, King Abdulaziz Medical City, Riyadh, Ministry of National Guard-Health Affairs, Riyadh, 14611, Saudi Arabia.
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
| | - Shaun Sabico
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia
| | | | - Amin Jayyousi
- Endocrine and Diabetes Section, Hamad Medical Corporation, Doha, Qatar
- Weill Cornell Medical College, Doha, Qatar
| | - Dalal Alromaihi
- King Hamad University Hospital, Busaiteen, Bahrain
- Medical University of Bahrain, Busaiteen, Bahrain
- Bahrain Diabetes Society, Manama, Bahrain
| | | | - Fatheya Alawadi
- Endocrine Department, Dubai Hospital, Dubai Health Authority, Dubai, United Arab Emirates
| | - Juma Alkaabi
- Department of Internal Medicine, College of Medicine, and Health Sciences, UAE University, Al Ain, United Arab Emirates
| | - Mohamed Hassanein
- Endocrine Department, Dubai Hospital, Dubai Health Authority, Dubai, United Arab Emirates
| | | | - Seham Saleh
- Prince Sultan Cardiac Center, Riyadh, Saudi Arabia
| | - Thamer Alessa
- Division of Endocrinology, Diabetes and Metabolism, Jaber Al-Ahmad Hospital, Kuwait City, Kuwait
- Dasman Diabetes Institute, Kuwait City, Kuwait
| | - Nasser M Al-Daghri
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia
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18
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AlSlail FY, Akil YA. Treatment Patterns, Effectiveness, and Satisfaction Among Patients with Type 2 Diabetes Treated with Insulin in Saudi Arabia: Results of the RIMODIS Study. Diabetes Ther 2021; 12:1965-1978. [PMID: 34117593 PMCID: PMC8266937 DOI: 10.1007/s13300-021-01089-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 05/26/2021] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION The alarming increase in type 2 diabetes mellitus (T2DM) in Saudi Arabia is aggravated by increasing obesity, sedentary lifestyle, and population aging. The RIMODIS study aimed at describing the practices in the therapeutic management of patients with T2DM treated with different insulin regimens. METHODS This national, multicenter, non-interventional, cross-sectional disease registry on the real-life therapeutic management of insulin-treated patients with T2DM in Saudi Arabia enrolled 3010 patients. It primarily aimed at describing treatment patterns, complications, and glycemia levels. Patients completed the diabetes treatment satisfaction questionnaire (DTSQ). Data on different treatment patterns were analyzed using chi-square or Fisher's exact test. Outcomes were analyzed according to the different insulin regimen subgroups (basal versus premixed). RESULTS Over 60% of patients were treated with premixed insulin and most patients were also prescribed oral antidiabetics (OADs). Patients on insulin alone seemed to achieve better glycated hemoglobin (HbA1c) control. Adding OADs to insulin slightly increased treatment satisfaction scores, with scores higher in patients on basal insulin compared to premixed insulin. Hypoglycemia was lower when adding OADs to insulin. Most patients showed high treatment adherence; however, two-thirds of study patients failed to achieve glycemic target levels. CONCLUSION Most patients are treated with a combination of insulin and OADs, associated with glycemic control and low incidence of hypoglycemia. However, we highlight suboptimal glycemic target achievement, underscoring the need to improve T2DM clinical management and promote healthier lifestyle among patients in Saudi Arabia.
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Affiliation(s)
- Fatima Y AlSlail
- National Diabetes Prevention and Control Program, Ministry of Health Central Directorate, Riyadh, Saudi Arabia.
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19
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Rojas M, Chávez-Castillo M, Bautista J, Ortega Á, Nava M, Salazar J, Díaz-Camargo E, Medina O, Rojas-Quintero J, Bermúdez V. Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links. World J Diabetes 2021; 12:745-766. [PMID: 34168725 PMCID: PMC8192246 DOI: 10.4239/wjd.v12.i6.745] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Revised: 03/20/2021] [Accepted: 05/21/2021] [Indexed: 02/06/2023] Open
Abstract
At present, Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are two highly prevalent disorders worldwide, especially among elderly individuals. T2DM appears to be associated with cognitive dysfunction, with a higher risk of developing neurocognitive disorders, including AD. These diseases have been observed to share various pathophysiological mechanisms, including alterations in insulin signaling, defects in glucose transporters (GLUTs), and mitochondrial dysfunctions in the brain. Therefore, the aim of this review is to summarize the current knowledge regarding the molecular mechanisms implicated in the association of these pathologies as well as recent therapeutic alternatives. In this context, the hyperphosphorylation of tau and the formation of neurofibrillary tangles have been associated with the dysfunction of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in the nervous tissues as well as the decrease in the expression of GLUT-1 and GLUT-3 in the different areas of the brain, increase in reactive oxygen species, and production of mitochondrial alterations that occur in T2DM. These findings have contributed to the implementation of overlapping pharmacological interventions based on the use of insulin and antidiabetic drugs, or, more recently, azeliragon, amylin, among others, which have shown possible beneficial effects in diabetic patients diagnosed with AD.
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Affiliation(s)
- Milagros Rojas
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela
| | - Mervin Chávez-Castillo
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela
| | - Jordan Bautista
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela
| | - Ángel Ortega
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela
| | - Manuel Nava
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela
| | - Juan Salazar
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela
| | - Edgar Díaz-Camargo
- Universidad Simón Bolívar, Facultad de Ciencias Jurídicas y Sociales, Cúcuta 540006, Colombia
| | - Oscar Medina
- Universidad Simón Bolívar, Facultad de Ciencias Jurídicas y Sociales, Cúcuta 540006, Colombia
| | - Joselyn Rojas-Quintero
- Pulmonary and Critical Care Medicine Department, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02155, United States
| | - Valmore Bermúdez
- Universidad Simón Bolívar, Facultad de Ciencias de la Salud, Barranquilla 080001, Colombia
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20
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Baye AM, Fanta TG, Siddiqui MK, Dawed AY. The Genetics of Adverse Drug Outcomes in Type 2 Diabetes: A Systematic Review. Front Genet 2021; 12:675053. [PMID: 34194474 PMCID: PMC8236944 DOI: 10.3389/fgene.2021.675053] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 05/21/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Adverse drug reactions (ADR) are a major clinical problem accounting for significant hospital admission rates, morbidity, mortality, and health care costs. One-third of people with diabetes experience at least one ADR. However, there is notable interindividual heterogeneity resulting in patient harm and unnecessary medical costs. Genomics is at the forefront of research to understand interindividual variability, and there are many genotype-drug response associations in diabetes with inconsistent findings. Here, we conducted a systematic review to comprehensively examine and synthesize the effect of genetic polymorphisms on the incidence of ADRs of oral glucose-lowering drugs in people with type 2 diabetes. Methods: A literature search was made to identify articles that included specific results of research on genetic polymorphism and adverse effects associated with oral glucose-lowering drugs. The electronic search was carried out on 3rd October 2020, through Cochrane Library, PubMed, and Web of Science using keywords and MeSH terms. Result: Eighteen articles consisting of 10, 383 subjects were included in this review. Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by SLC22A1) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by SLC29A4) or serotonin transporter (SERT, encoded by SLC6A4) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects. These effects were shown to exacerbate by concomitant treatment with gut transporter inhibiting drugs. The CYP2C9 alleles, *2 (rs1799853C>T) and *3 (rs1057910A>C) that are predictive of low enzyme activity were more common in subjects who experienced hypoglycemia after treatment with sulfonylureas. However, there was no significant association between sulfonylurea-related hypoglycemia and genetic variants in the ATP-binding cassette transporter sub-family C member 8 (ABCC8)/Potassium Inwardly Rectifying Channel Subfamily J Member 11 (KCNJ11). Compared to the wild type, the low enzyme activity C allele at CYP2C8*3 (rs1057910A>C) was associated with less weight gain whereas the C allele at rs6123045 in the NFATC2 gene was significantly associated with edema from rosiglitazone treatment. Conclusion: In spite of limited studies investigating genetics and ADR in diabetes, some convincing results are emerging. Genetic variants in genes encoding drug transporters and metabolizing enzymes are implicated in metformin-related GI adverse effects, and sulfonylurea-induced hypoglycemia, respectively. Further studies to investigate newer antidiabetic drugs such as DPP-4i, GLP-1RA, and SGLT2i are warranted. In addition, pharmacogenetic studies that account for race and ethnic differences are required.
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Affiliation(s)
- Assefa M Baye
- Department of Pharmacology and Clinical Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Teferi G Fanta
- Department of Pharmacology and Clinical Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Moneeza K Siddiqui
- Division of Population Health and Genomics, Ninewells Hospital and School of Medicine, University of Dundee, Dundee, United Kingdom
| | - Adem Y Dawed
- Division of Population Health and Genomics, Ninewells Hospital and School of Medicine, University of Dundee, Dundee, United Kingdom
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21
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Ragia G, Katsika E, Ioannou C, Manolopoulos VG. TCF7L2 rs7903146 C>T gene polymorphism is not associated with hypoglycemia in sulfonylurea-treated type 2 diabetic patients. DRUG METABOLISM AND DRUG INTERACTIONS 2021; 36:165-168. [DOI: 10.1515/dmpt-2020-0168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Abstract
Objectives
Hypoglycemia is the most common adverse effect of sulfonylureas (SUs) and a major concern when using these drugs. Transcription factor 7-like 2 (TCF7L2) rs7903146 C>T polymorphism is an established and well characterized genetic marker of type 2 diabetes (T2DM) risk. The aim of the present study was to analyze the potential association of TCF7L2 rs7903146 C>T polymorphism with SU-induced hypoglycemia in a well characterized cohort of SU-treated patients previously genotyped for cytochrome P450 2C9 (CYP2C9) and P450 oxidoreductase (POR).
Methods
The study group consisted of 176 SU-treated T2DM patients of whom 92 had experienced at least one drug-associated hypoglycemic event. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for TCF7L2 rs7903146 genotyping.
Results
TCF7L2 rs7903146 C>T genotype and allele frequency did not differ between cases and controls (p=0.745 and 0.671, respectively). In logistic regression analysis adjusted for other factors affecting hypoglycemia, including CYP2C9 and POR genotypes, TCF7L2 rs7903146 C>T polymorphism did not increase the risk of hypoglycemia (OR=1.238, 95% C.I.=0.750–2.044, p=0.405).
Conclusions
TCF7L2 rs7903146 C>T polymorphism is not associated with SU-induced hypoglycemia. Identifying additional gene polymorphisms associated with SU-induced hypoglycemia is crucial for improving T2DM patient therapy with SUs.
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Affiliation(s)
- Georgia Ragia
- Laboratory of Pharmacology , Medical School, Democritus University of Thrace , Alexandroupolis , Greece
| | - Evgenia Katsika
- Laboratory of Pharmacology , Medical School, Democritus University of Thrace , Alexandroupolis , Greece
| | - Charalampia Ioannou
- Laboratory of Pharmacology , Medical School, Democritus University of Thrace , Alexandroupolis , Greece
| | - Vangelis G. Manolopoulos
- Laboratory of Pharmacology , Medical School, Democritus University of Thrace , Alexandroupolis , Greece
- Clinical Pharmacology and Pharmacogenetics Unit , Academic General Hospital of Alexandroupolis , Alexandroupolis , Greece
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Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype. J Pers Med 2021; 11:jpm11050367. [PMID: 34063566 PMCID: PMC8147656 DOI: 10.3390/jpm11050367] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 04/03/2021] [Accepted: 04/08/2021] [Indexed: 12/13/2022] Open
Abstract
The antidiabetic drug gliclazide is partly metabolized by CYP2C19, the main enzyme involved in omeprazole metabolism. The aim of the study was to explore the interaction between omeprazole and gliclazide in relation to CYP2C19 phenotype using physiologically based pharmacokinetic (PBPK) modeling approach. Developed PBPK models were verified using in vivo pharmacokinetic profiles obtained from a clinical trial on omeprazole-gliclazide interaction in healthy volunteers, CYP2C19 normal/rapid/ultrarapid metabolizers (NM/RM/UM). In addition, the association of omeprazole cotreatment with gliclazide-induced hypoglycemia was explored in 267 patients with type 2 diabetes (T2D) from the GoDARTS cohort, Scotland. The PBPK simulations predicted 1.4–1.6-fold higher gliclazide area under the curve (AUC) after 5-day treatment with 20 mg omeprazole in all CYP2C19 phenotype groups except in poor metabolizers. The predicted gliclazide AUC increased 2.1 and 2.5-fold in intermediate metabolizers, and 2.6- and 3.8-fold in NM/RM/UM group, after simulated 20-day dosing with 40 mg omeprazole once and twice daily, respectively. The predicted results were corroborated by findings in patients with T2D which demonstrated 3.3-fold higher odds of severe gliclazide-induced hypoglycemia in NM/RM/UM patients concomitantly treated with omeprazole. Our results indicate that omeprazole may increase exposure to gliclazide and thus increase the risk of gliclazide-associated hypoglycemia in the majority of patients.
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Scheen AJ. Careful use to minimize adverse events of oral antidiabetic medications in the elderly. Expert Opin Pharmacother 2021; 22:2149-2165. [PMID: 33823723 DOI: 10.1080/14656566.2021.1912735] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION An increasing number of older patients has type 2 diabetes treated with different oral antidiabetic agents whose safety may raise concern considering some particularities of a heterogeneous elderly population. AREAS COVERED This article discusses some characteristics of older patients that could increase the risk of adverse events, with a focus on hypoglycemia. It describes the most frequent and/or severe complications reported in the elderly in both randomized controlled trials and observational studies with metformin, sulfonylureas, meglitinides, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors (gliptins) and sodium-glucose cotransporter type 2 inhibitors (gliflozins). EXPERT OPINION Old patients may present comorbidities (renal impairment, vascular disease, heart failure, risk of dehydration, osteoporosis, cognitive dysfunction) that could increase the risk of severe adverse events. Sulfonylureas (and meglitinides) induce hypoglycemia, which may be associated with falls/fractures and cardiovascular events. Medications lacking hypoglycemia should be preferred. Gliptins appear to have the best tolerance/safety profile whereas gliflozins exert a cardiorenal protection. However, data are lacking in very old or frailty old patients so that caution and appropriate supervision of such patients are required. Taking advantage of a large choice of pharmacotherapies, personalized treatment is recommended based upon both drug safety profiles and old patient individual characteristics.
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Affiliation(s)
- André J Scheen
- Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium.,Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, Liège, Belgium
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Santos A, Magro DO, Evangelista-Poderoso R, Saad MJA. Diabetes, obesity, and insulin resistance in COVID-19: molecular interrelationship and therapeutic implications. Diabetol Metab Syndr 2021; 13:23. [PMID: 33648564 PMCID: PMC7919999 DOI: 10.1186/s13098-021-00639-2] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Revised: 02/05/2021] [Accepted: 02/13/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Our understanding of the pathophysiology of the COVID-19 manifestations and evolution has improved over the past 10 months, but the reasons why evolution is more severe in obese and diabetic patients are not yet completely understood. MAIN TEXT In the present review we discuss the different mechanisms that may contribute to explain the pathophysiology of COVID-19 including viral entrance, direct viral toxicity, endothelial dysfunction, thromboinflammation, dysregulation of the immune response, and the renin-angiotensin-aldosterone system. CONCLUSIONS We show that the viral infection activates an integrated stress response, including activations of serine kinases such as PKR and PERK, which induce IRS-1 serine phosphorylation and insulin resistance. In parallel, we correlate and show the synergy of the insulin resistance of COVID-19 with this hormonal resistance of obesity and diabetes, which increase the severity of the disease. Finally, we discuss the potential beneficial effects of drugs used to treat insulin resistance and diabetes in patients with COVID-19.
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Affiliation(s)
- Andrey Santos
- Department of Internal Medicine-FCM, State University of Campinas-UNICAMP, Campinas, SP, Brazil
| | - Daniéla Oliveira Magro
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas-UNICAMP, Campinas, SP, Brazil
| | | | - Mario José Abdalla Saad
- Department of Internal Medicine-FCM, State University of Campinas-UNICAMP, Campinas, SP, Brazil.
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Nocturnal Hypoglycaemia in Patients with Diabetes Mellitus: Database Analysis of a Cohort Using Telemedicine Support for Self-Monitoring of Blood Glucose over a 10-Year-Long Period. MEDICINA-LITHUANIA 2021; 57:medicina57020167. [PMID: 33672913 PMCID: PMC7918473 DOI: 10.3390/medicina57020167] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/27/2021] [Accepted: 02/08/2021] [Indexed: 01/09/2023]
Abstract
Background and Objectives: In patients with diabetes mellitus, hypoglycaemic episodes, especially during night hours, carry a significant risk. Data about the occurrence of nocturnal hypoglycaemia in real-world settings are of clinical importance. The aim of our study was to evaluate the occurrence of nocturnal hypoglycaemia among patients with diabetes using self-monitoring of blood glucose (SMBG) with telemedicine support. Materials and Methods: We retrospectively analysed the central database of an internet-based supportive system between 2010 and 2020 when 8190 SMBG users uploaded nearly 10 million capillary blood glucose values. Nocturnal hypoglycaemia was defined as capillary blood glucose < 3.0 mmol/L measured between 00:00 and 05:59 h. Results: The database contained 914,146 nocturnal blood glucose values from 7298 users; 24,623 (2.7%) glucose values were below the hypoglycaemic threshold and 2363 patients (32.4%) had at least one hypoglycaemic glucose value. Nocturnal hypoglycaemia was more often found in patients with type 1 vs. type 2 diabetes (n = 1890 (80.0%) vs. n = 387 (16.4%), respectively). Hypoglycaemic blood glucose values were most frequently observed in the age group of 10.0–19.9 years (n = 481 (20.4%)). Patients with nocturnal hypoglycaemia were mostly on insulin treatment (1854 (78.5%) patients with 20,727 (84.1%) hypoglycaemic glucose values). Only 356 patients (15.1%) with nocturnal hypoglycaemia performed a retest within 120 min. Within a one-day-long (1440 min) timeframe, the elapsed median time until a retest, yielding a safe blood glucose value (>3.9 mml/L), was 273 min (interquartile range: 157–300 min). Conclusions: Nocturnal hypoglycaemia should be considered as a persisting challenge to antihyperglycaemic treatment in patients living with diabetes. Continuous efforts are needed to improve both antihyperglycaemic treatment and patient education for preventing nocturnal hypoglycaemia, and to act adequately if hypoglycaemic values are detected.
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Nguyen JV, Roseberry S, Rivas JA, Cauthon KAB. Hypoglycemia in Older People With Type 2 Diabetes: Prevention and Treatment Strategies for Outpatient and Long-Term Care Facility Settings. Sr Care Pharm 2021; 36:112-123. [PMID: 33509335 DOI: 10.4140/tcp.n.2021.112] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Hypoglycemia in the older population is a significant problem accounting for increased hospitalizations, emergency room visits, health care costs, and decreased quality of life. Older patients are more susceptible to hypoglycemia because of the increased prevalence of comorbidities requiring multiple medications, age-related physiologic changes, and a progressive decline in health. Older patients are less likely to present with symptoms of hypoglycemia and symptoms may frequently appear at a lower threshold of blood glucose than in younger patients. Consequently, preventing and treating hyperglycemia in older patients can be challenging. If mismanaged, the impact of hypoglycemia in these patients can lead to acute and chronic negative outcomes. Insulin and sulfonylureas should be closely monitored, and deprescribing should be routinely considered in older patients at high risk for hypoglycemia.
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Ragia G, Katsika E, Ioannou C, Manolopoulos VG. TCF7L2 rs7903146 C>T gene polymorphism is not associated with hypoglycemia in sulfonylurea-treated type 2 diabetic patients. Drug Metab Pers Ther 2020; 0:dmdi-2020-0168. [PMID: 33780196 DOI: 10.1515/dmdi-2020-0168] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 12/06/2020] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Hypoglycemia is the most common adverse effect of sulfonylureas (SUs) and a major concern when using these drugs. Transcription factor 7-like 2 (TCF7L2) rs7903146 C>T polymorphism is an established and well characterized genetic marker of type 2 diabetes (T2DM) risk. The aim of the present study was to analyze the potential association of TCF7L2 rs7903146 C>T polymorphism with SU-induced hypoglycemia in a well characterized cohort of SU-treated patients previously genotyped for cytochrome P450 2C9 (CYP2C9) and P450 oxidoreductase (POR). METHODS The study group consisted of 176 SU-treated T2DM patients of whom 92 had experienced at least one drug-associated hypoglycemic event. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for TCF7L2 rs7903146 genotyping. RESULTS TCF7L2 rs7903146 C>T genotype and allele frequency did not differ between cases and controls (p=0.745 and 0.671, respectively). In logistic regression analysis adjusted for other factors affecting hypoglycemia, including CYP2C9 and POR genotypes, TCF7L2 rs7903146 C>T polymorphism did not increase the risk of hypoglycemia (OR=1.238, 95% C.I.=0.750-2.044, p=0.405). CONCLUSIONS TCF7L2 rs7903146 C>T polymorphism is not associated with SU-induced hypoglycemia. Identifying additional gene polymorphisms associated with SU-induced hypoglycemia is crucial for improving T2DM patient therapy with SUs.
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Affiliation(s)
- Georgia Ragia
- Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
| | - Evgenia Katsika
- Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
| | - Charalampia Ioannou
- Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
| | - Vangelis G Manolopoulos
- Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
- Clinical Pharmacology and Pharmacogenetics Unit, Academic General Hospital of Alexandroupolis, Alexandroupolis, Greece
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Duffy S, Norton D, Kelly M, Chavez A, Tun R, Ramírez MNDG, Chen G, Wise P, Svenson J. Using Community Health Workers and a Smartphone Application to Improve Diabetes Control in Rural Guatemala. GLOBAL HEALTH, SCIENCE AND PRACTICE 2020; 8:699-720. [PMID: 33361237 PMCID: PMC7784066 DOI: 10.9745/ghsp-d-20-00076] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 09/01/2020] [Indexed: 11/15/2022]
Abstract
BACKGROUND The global prevalence of diabetes has nearly doubled since 1980. Seventy-five percent of patients with diabetes live in low- and middle-income countries, such as Guatemala, where health care systems are often poorly equipped for chronic disease management. Community health workers (CHWs) and mobile health technology have increasingly been applied to the diabetes epidemic in these settings, although mostly in supportive rather than primary roles in diabetes management. We sought to improve diabetes care in rural Guatemala through the development of a CHW-led diabetes program and a smartphone application to provide CHWs with clinical decision support. METHODS We worked with our local partners to develop a program model and the smartphone application (using the CommCare platform) and to train CHWs. We recruited patients with type 2 diabetes living in rural communities. Program evaluation used a single-group, pre-post design. Primary outcomes were hemoglobin A1c and the percentage of patients meeting A1c goals compared with baseline. We also followed a variety of process metrics, including application reliability. RESULTS Eighty-nine patients enrolled during the study period. The hemoglobin A1c percentage decreased significantly at 3 months (-1.0; 95% CI=-1.7, -0.6), 6 months (-1.5; 95% CI=-2.2, -0.8), 9 months (-1.3; 95% CI=-2.0, -0.6), and 12 months (-1.0; 95% CI=-1.7, -0.4). The percentage of patients with A1c ≤ 8% increased significantly at 3 months (23.6% to 44.4%, P=.007), 6 months (22.0% to 44.0%, P=.015), and 9 months (23.9% to 45.7%, P=.03). CHWs and supervising physicians agreed with application medication recommendations >90% of the time. CONCLUSION Our results suggest that CHWs can safely and effectively manage diabetes with the assistance of a smartphone application and remote physician supervision. This model should be evaluated versus other standards of care and could be adapted to other low-resource settings and chronic diseases.
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Affiliation(s)
- Sean Duffy
- University of Wisconsin School of Medicine and Public Health, Department of Family Medicine and Community Health, Madison, WI, USA.
| | - Derek Norton
- University of Wisconsin School of Medicine and Public Health, Department of Biostatistics and Medical Informatics, Madison, WI, USA
| | - Mark Kelly
- University of California-Los Angeles David Geffen School of Medicine, Internal Medicine Residency Program, Los Angeles, CA, USA
| | | | - Rafael Tun
- Hospital Obras Sociales Monseñor Gregorio Schaffer, San Lucas Tolimán, Guatemala
| | - Mariana Niño de Guzmán Ramírez
- University of Wisconsin School of Medicine and Public Health, Department of Family Medicine and Community Health, Madison, WI, USA
| | - Guanhua Chen
- University of Wisconsin School of Medicine and Public Health, Department of Biostatistics and Medical Informatics, Madison, WI, USA
| | - Paul Wise
- Stanford University School of Medicine, Stanford, CA, USA
| | - Jim Svenson
- University of Wisconsin School of Medicine and Public Health, Department of Emergency Medicine, Madison, WI, USA
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Alwafi H, Alsharif AA, Wei L, Langan D, Naser AY, Mongkhon P, Bell JS, Ilomaki J, Al Metwazi MS, Man KKC, Fang G, Wong ICK. Incidence and prevalence of hypoglycaemia in type 1 and type 2 diabetes individuals: A systematic review and meta-analysis. Diabetes Res Clin Pract 2020; 170:108522. [PMID: 33096187 DOI: 10.1016/j.diabres.2020.108522] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 09/30/2020] [Accepted: 10/13/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Previous meta-analysis investigating the incidence and prevalence of hypoglycaemia in both types of diabetes is limited. The purpose of this review is to conduct a systematic review and meta-analysis of the existing literature which investigates the incidence and prevalence of hypoglycaemia in individuals with diabetes. METHODS PubMed, Embase and Cochrane library databases were searched up to October 2018. Observational studies including individuals with diabetes of all ages and reporting incidence and/or prevalence of hypoglycaemia were included. Two reviewers independently screened articles, extracted data and assessed the quality of included studies. Meta-analysis was performed using a random effects model with 95% confidence interval (CI) to estimate the pooled incidence and prevalence of hypoglycaemia in individuals with diabetes. RESULTS Our search strategy generated 35,007 articles, of which 72 studies matched the inclusion criteria and were included in the meta-analysis. The prevalence of hypoglycaemia ranged from 0.074% to 73.0%, comprising a total of 2,462,810 individuals with diabetes. The incidence rate of hypoglycaemia ranged from 0.072 to 42,890 episodes per 1,000 person-years: stratified by type of diabetes, it ranged from 14.5 to 42,890 episodes per 1,000 person-years and from 0.072 to 16,360 episodes per 1,000-person years in type 1 and type 2 diabetes, respectively. CONCLUSION Hypoglycaemia is very common among individuals with diabetes. Further studies are needed to investigate hypoglycaemia-associated risk factors.
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Affiliation(s)
- Hassan Alwafi
- Research Department of Practice and Policy, School of Pharmacy, University College London (UCL), London, United Kingdom; Faculty of Medicine, Umm Al Qura University, Mecca, Saudi Arabia
| | - Alaa A Alsharif
- Department of Pharmacy Practice, Faculty of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Li Wei
- Research Department of Practice and Policy, School of Pharmacy, University College London (UCL), London, United Kingdom
| | - Dean Langan
- UCL Great Ormond Street Institute of Child Health, London, United Kingdom
| | | | - Pajaree Mongkhon
- Department of Pharmacy Practice School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand; Pharmacoepidemiology and Statistics Research Center (PESRC), Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
| | - J Simon Bell
- Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Australia
| | - Jenni Ilomaki
- Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Australia
| | - Mansour S Al Metwazi
- Clinical Pharmacy Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Kenneth K C Man
- Research Department of Practice and Policy, School of Pharmacy, University College London (UCL), London, United Kingdom; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Gang Fang
- Division of Pharmaceutical Outcomes and Policy, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
| | - Ian C K Wong
- Research Department of Practice and Policy, School of Pharmacy, University College London (UCL), London, United Kingdom; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; The University of Hong Kong - Shenzhen Hospital, 1, Haiyuan 1st Road, Futian District, Shenzhen, Guangdong, China.
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30
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Hasan SS, Kow CS, Bain A, Kavanagh S, Merchant HA, Hadi MA. Pharmacotherapeutic considerations for the management of diabetes mellitus among hospitalized COVID-19 patients. Expert Opin Pharmacother 2020; 22:229-240. [PMID: 33054481 DOI: 10.1080/14656566.2020.1837114] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Diabetes mellitus is one of the most prevalent comorbidities identified in patients with coronavirus disease 2019 (COVID-19). This article aims to discuss the pharmacotherapeutic considerations for the management of diabetes in hospitalized patients with COVID-19. AREAS COVERED We discussed various aspects of pharmacotherapeutic management in hospitalized patients with COVID-19: (i) susceptibility and severity of COVID-19 among individuals with diabetes, (ii) glycemic goals for hospitalized patients with COVID-19 and concurrent diabetes, (iii) pharmacological treatment considerations for hospitalized patients with COVID-19 and concurrent diabetes. EXPERT OPINION The glycemic goals in patients with COVID-19 and concurrent type 1 (T1DM) or type 2 diabetes (T2DM) are to avoid disruption of stable metabolic state, maintain optimal glycemic control, and prevent adverse glycemic events. Patients with T1DM require insulin therapy at all times to prevent ketosis. The management strategies for patients with T2DM include temporary discontinuation of certain oral antidiabetic agents and consideration for insulin therapy. Patients with T2DM who are relatively stable and able to eat regularly may continue with oral antidiabetic agents if glycemic control is satisfactory. Hyperglycemia may develop in patients with systemic corticosteroid treatment and should be managed upon accordingly.
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Affiliation(s)
| | - Chia Siang Kow
- School of Postgraduate Studies, International Medical University , Kuala Lumpur, Malaysia
| | - Amie Bain
- Department of Pharmacy, University of Huddersfield , Huddersfield, UK.,Department of Pharmacy, Sheffield Teaching Hospitals NHS Foundation Trust , Sheffield, UK
| | - Sallianne Kavanagh
- Department of Pharmacy, University of Huddersfield , Huddersfield, UK.,Department of Pharmacy, Sheffield Teaching Hospitals NHS Foundation Trust , Sheffield, UK
| | - Hamid A Merchant
- Department of Pharmacy, University of Huddersfield , Huddersfield, UK
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Chung W, Promrat K, Wands J. Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases. World J Hepatol 2020; 12:533-557. [PMID: 33033564 PMCID: PMC7522556 DOI: 10.4254/wjh.v12.i9.533] [Citation(s) in RCA: 10] [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: 07/08/2020] [Revised: 08/03/2020] [Accepted: 08/15/2020] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) negatively affects the development and progression of chronic liver diseases (CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma (HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.
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Affiliation(s)
- Waihong Chung
- Division of Gastroenterology, Department of Medicine, Rhode Island Hospital, Providence, RI 02905, United States.
| | - Kittichai Promrat
- Division of Gastroenterology and Hepatology, Providence VA Medical Center, Providence, RI 02908, United States
| | - Jack Wands
- Liver Research Center, The Warren Alpert Medical School of Brown University, Providence, RI 02903, United States
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Tsoutsouki J, Wunna W, Chowdhury A, Chowdhury TA. Advances in the management of diabetes: therapies for type 2 diabetes. Postgrad Med J 2020; 96:610-618. [DOI: 10.1136/postgradmedj-2019-137404] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 04/28/2020] [Accepted: 04/29/2020] [Indexed: 12/15/2022]
Abstract
The incidence of type 2 diabetes is rapidly rising worldwide leading to an increasing burden of cardiovascular and microvascular complications. The aim of treatment of the condition is to improve quality of life and reduce such complications. To this end, improvement in glucose control remains an important consideration. In recent years, important therapeutic advances have occurred in the management of hyperglycaemia in people with type 2 diabetes. These include the use of dipeptidylpeptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium glucose transporter-2 inhibitors. The latter two classes appear to have some specific beneficial effects on cardiovascular and renal outcomes, independent of their antihyperglycaemic effects. This review aims to outline the current state of diagnosis and management of diabetes for the general physician, with a particular focus on new therapeutic agents for management of glucose in patients with type 2 diabetes.
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Lv W, Wang X, Xu Q, Lu W. Mechanisms and Characteristics of Sulfonylureas and Glinides. Curr Top Med Chem 2020; 20:37-56. [PMID: 31884929 DOI: 10.2174/1568026620666191224141617] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 08/30/2019] [Accepted: 09/22/2019] [Indexed: 12/25/2022]
Abstract
BACKGROUND Type 2 diabetes mellitus is a complex progressive endocrine disease characterized by hyperglycemia and life-threatening complications. It is the most common disorder of pancreatic cell function that causes insulin deficiency. Sulfonylurea is a class of oral hypoglycemic drugs. Over the past half century, these drugs, together with the subsequent non-sulfonylureas (glinides), have been the main oral drugs for insulin secretion. OBJECTIVE Through in-depth study, the medical profession considers it as an important drug for improving blood sugar control. METHODS The mechanism, characteristics, efficacy and side effects of sulfonylureas and glinides were reviewed in detail. RESULTS Sulfonylureas and glinides not only stimulated the release of insulin from pancreatic cells, but also had many extrapanular hypoglycemic effect, such as reducing the clearance rate of insulin in liver, reducing the secretion of glucagon, and enhancing the sensitivity of peripheral tissues to insulin in type 2 diabetes mellitus. CONCLUSION Sulfonylureas and glinides are effective first-line drugs for the treatment of diabetes mellitus. Although they have the risk of hypoglycemia, weight gain and cardiovascular disease, their clinical practicability and safety can be guaranteed as long as they are reasonably used.
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Affiliation(s)
- Wei Lv
- School of Materials Science and Engineering, Shanghai University, Shanghai, China.,Shanghai Huayi Resins Co., Ltd., Shanghai, China
| | - Xianqing Wang
- Charles Institute of Dermatology, University College Dublin, Dublin D04 V1W8, Ireland
| | - Qian Xu
- Charles Institute of Dermatology, University College Dublin, Dublin D04 V1W8, Ireland
| | - Wencong Lu
- School of Materials Science and Engineering, Shanghai University, Shanghai, China
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Mohan V, Khunti K, Chan SP, Filho FF, Tran NQ, Ramaiya K, Joshi S, Mithal A, Mbaye MN, Nicodemus NA, Latt TS, Ji L, Elebrashy IN, Mbanya JC. Management of Type 2 Diabetes in Developing Countries: Balancing Optimal Glycaemic Control and Outcomes with Affordability and Accessibility to Treatment. Diabetes Ther 2020; 11:15-35. [PMID: 31773420 PMCID: PMC6965543 DOI: 10.1007/s13300-019-00733-9] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Indexed: 12/18/2022] Open
Abstract
With the growing prevalence of type 2 diabetes, particularly in emerging countries, its management in the context of available resources should be considered. International guidelines, while comprehensive and scientifically valid, may not be appropriate for regions such as Asia, Latin America or Africa, where epidemiology, patient phenotypes, cultural conditions and socioeconomic status are different from America and Europe. Although glycaemic control and reduction of micro- and macrovascular outcomes remain essential aspects of treatment, access and cost are major limiting factors; therefore, a pragmatic approach is required in restricted-resource settings. Newer agents, such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in particular, are relatively expensive, with limited availability despite potentially being valuable for patients with insulin resistance and cardiovascular complications. This review makes a case for the role of more accessible second-line treatments with long-established efficacy and affordability, such as sulfonylureas, in the management of type 2 diabetes, particularly in developing or restricted-resource countries.
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Affiliation(s)
- Viswanathan Mohan
- Dr. Mohan's Diabetes Specialities Centre and Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India.
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester, UK
| | - Siew P Chan
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Fadlo F Filho
- Faculty of Medicine, ABC Foundation, Santo André, Brazil
| | - Nam Q Tran
- Department of Endocrinology, University Medical Center, Ho Chi Minh City, Vietnam
| | - Kaushik Ramaiya
- Shree Hindu Mandal Hospital, Dar es Salaam, Tanzania
- Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Shashank Joshi
- Lilavati Hospital and Research Centre, Mumbai, Maharashtra, India
| | | | | | - Nemencio A Nicodemus
- Department of Medicine, University of the Philippines-Philippine General Hospital, Manila, Philippines
- Department of Biochemistry and Molecular Biology, University of the Philippines-College of Medicine, Manila, Philippines
| | - Tint S Latt
- Department of Diabetes and Endocrinology, University of Medicine 2, Yangon, Myanmar
| | - Linong Ji
- Department of Endocrinology, Peking University People's Hospital, Beijing, China
| | - Ibrahim N Elebrashy
- Department of Internal Medicine, Diabetes, and Endocrinology, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Jean C Mbanya
- University of Yaoundé I, Yaoundé, Cameroon
- National Obesity Center, Central Hospital of Yaoundé, Yaoundé, Cameroon
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35
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Wu L, Gunton JE. The Changing Landscape of Pharmacotherapy for Diabetes Mellitus: A Review of Cardiovascular Outcomes. Int J Mol Sci 2019; 20:E5853. [PMID: 31766545 PMCID: PMC6928800 DOI: 10.3390/ijms20235853] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 11/16/2019] [Accepted: 11/18/2019] [Indexed: 12/16/2022] Open
Abstract
The prevention of cardiovascular morbidity and mortality has always been a primary concern in patients with type 2 diabetes. Modern trials of glucose-lowering therapies now assess major adverse cardiac events as an endpoint in addition to the effects on glycaemic control. Whilst the data on the efficacy of intensive glucose lowering on reducing cardiovascular risk are limited, there are now increasing numbers of glucose-lowering therapies that have proven cardiovascular benefit independent of glucose lowering. This review will summarise the available literature on cardiovascular outcomes in relation to metformin, sulphonylureas, di-peptidyl peptidase-4 inhibitors, glucagon-like peptide receptor agonists, sodium-glucose co-transporter 2 inhibitors, thiazolidinediones, acarbose and insulin. In addition, new paradigms in diabetes management and the importance of treatment selection based on considerations including but not limited to glycaemic control will be discussed.
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Affiliation(s)
- Linda Wu
- Department of Endocrinology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia
| | - Jenny E. Gunton
- Centre for Diabetes, Obesity and Endocrinology, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia;
- Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia
- Garvan Institute of Medical Research, Darlinghurst, NSW 2145, Australia
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Webb DR, Davies MJ, Jarvis J, Seidu S, Khunti K. The right place for Sulphonylureas today. Diabetes Res Clin Pract 2019; 157:107836. [PMID: 31479704 DOI: 10.1016/j.diabres.2019.107836] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 08/22/2019] [Indexed: 12/28/2022]
Abstract
The place of Sulphonylurea based insulin secretagogues in the management of Type 2 diabetes appears as controversial today as it was fifty years ago. Newer therapies are associated with less hypoglycaemia and weight gain than Sulphonylureas but currently cost more and lack assurances which come with long-term exposure. Emergence of recent CVOT data for SGLT-2 inhibitors and GLP-1 receptor agonists is likely to influence therapeutic choices and guidance is now supportive of their earlier use in cases at high risk of cardiovascular disease. Meta-analyses of Sulphonylurea trials have failed to indicate a consistent effect (positive or negative) on cardiovascular disease or mortality, although are limited by the relative scarcity of studies directly reporting these outcomes. The CAROLINA trial is reassuring in demonstrating cardiovascular safety for the Sulphonylurea Glimepiride when compared directly with the DPP-4 inhibitor Linagliptin, suggesting either of these agents would be relatively safe second line options after Metformin in the majority of patients. This review provides a balanced assessment of available Sulphonylurea treatments in the context of current cardiovascular outcome trial data (CVOT) data and hopefully assists informed decision making about the place of these drugs in contemporary glucose lowering practice.
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Affiliation(s)
- David R Webb
- University of Leicester, Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
| | - Melanie J Davies
- University of Leicester, Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
| | - Janet Jarvis
- University Hospitals of Leicester NHS Trust, Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
| | - Sam Seidu
- University of Leicester, Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
| | - Kamlesh Khunti
- University of Leicester, Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
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National ambulatory care non-insulin antidiabetic medication prescribing trends in the United States from 2009 to 2015. PLoS One 2019; 14:e0221174. [PMID: 31412090 PMCID: PMC6693747 DOI: 10.1371/journal.pone.0221174] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 07/31/2019] [Indexed: 01/01/2023] Open
Abstract
OBJECTIVE Despite their efficacy in lowering hemoglobin A1c, recent data suggest that sulfonylureas are associated with cardiovascular risk and hypoglycemia. The objective of this study was to determine whether prescribers decreased sulfonylurea use in favor of newer medications in the United States over seven years. RESEARCH DESIGN AND METHODS This cross-sectional study utilized data from the Centers for Disease Control and Prevention's National Ambulatory Medical Care Survey. Patient visits between 2009 and 2015 were included for patients who were at least 18 years old, had a documented prescription for a non-insulin antidiabetic medication, and a diagnosis of type 2 diabetes. Sample survey data were extrapolated to national estimates using data weights. Prescribing rates were calculated as the number of visits with a documented medication class divided by the total number of visits with a prescription for any diabetes medication class, times 100%. RESULTS A total of 303 million patient visits were included in this study. The median (IQR) patient age was 64 (55-73) years old and 49.8% were male. Sulfonylurea prescribing rates decreased from 43% in 2009 to 36.5% in 2015. Prescribing of GLP-1 receptor agonists increased from 2009 to 2014 (3.95% to 5.30%), but then decreased to 4.19% in 2015. SGLT-2 inhibitor prescribing began in 2013 and increased to 7.3% by 2015. Metformin prescribing remained relatively stable over the study period (range 70% to 72%). CONCLUSIONS National ambulatory sulfonylurea prescribing decreased from 2009 to 2015 with a corresponding increase in newer non-insulin antidiabetic agent prescribing.
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Garla V, Kanduri S, Yanes-Cardozo L, Lién LF. Management of diabetes mellitus in chronic kidney disease. MINERVA ENDOCRINOL 2019; 44:273-287. [DOI: 10.23736/s0391-1977.19.03015-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Tan YZ, Cheen MHH, Goh SY, Bee YM, Lim PS, Khee GY, Thumboo J. Trends in medication utilization, glycemic control and outcomes among type 2 diabetes patients in a tertiary referral center in Singapore from 2007 to 2017. J Diabetes 2019; 11:573-581. [PMID: 30556375 DOI: 10.1111/1753-0407.12886] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Revised: 11/08/2018] [Accepted: 12/04/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Use of glucose-lowering agents is a cornerstone in combating type 2 diabetes (T2DM). Treatment guidelines have changed significantly over the past decade. We report temporal trends in medication utilization, glycemic control and rate of severe hypoglycemia in T2DM patients at a tertiary referral center in Singapore. METHODS We analyzed data of 36 924 T2DM patients seen at Singapore General Hospital from 2007 to 2017. Annual age-, sex- and racially-standardized proportions of patients (a) prescribed with each class of glucose-lowering agent, (b) on various glucose-lowering regimens, and (c) had an HbA1c of less than 6%, 6% to less than 7%, 7% to less than 8%, 8% to less than 9%, or 9% or more were estimated using logistic regression. Poisson regression was used to estimate standardized rate of severe hypoglycemia. RESULTS From 2007 to 2017, use of metformin (45.9% to 59.6%) and insulin (24.4% to 57.9%) increased, while utilization of sulfonylureas (52.0% to 44.9%) decreased (all P < 0.001). Utilization of dipeptidyl peptidase-4 inhibitors (1.2% to 31.2%) and sodium-glucose cotransporter-2 inhibitors (0.5% to 7.4%) increased from 2008 to 2017 and 2012 to 2017, respectively (all P < 0.001). More patients were prescribed a combination of insulin and oral agents (17.3% to 46.0%, P < 0.001). The proportion of patients with HbA1c of 8% or more increased (33.7% to 36.0%, P < 0.001). Rates of severe hypoglycemia (5.0 to 8.4 per 100 patient-years, P < 0.001) also rose. CONCLUSION Medication utilization patterns have changed significantly over the past 11 years with a shift towards newer agents. Glycemic control has remained stable, and rate of severe hypoglycemia increased. Further analysis is required before causal relationships can be inferred.
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Affiliation(s)
- Yan Zhi Tan
- Department of Pharmacy, Singapore General Hospital, Singapore
| | | | - Su-Yen Goh
- Department of Endocrinology, Singapore General Hospital, Singapore
| | - Yong Mong Bee
- Department of Endocrinology, Singapore General Hospital, Singapore
| | - Paik Shia Lim
- Department of Pharmacy, Singapore General Hospital, Singapore
| | - Giat Yeng Khee
- Department of Pharmacy, Singapore General Hospital, Singapore
| | - Julian Thumboo
- Department of Rheumatology and Immunology, Singapore General Hospital, Singapore
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Picke AK, Campbell G, Napoli N, Hofbauer LC, Rauner M. Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties. Endocr Connect 2019; 8:R55-R70. [PMID: 30772871 PMCID: PMC6391903 DOI: 10.1530/ec-18-0456] [Citation(s) in RCA: 92] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 01/24/2019] [Indexed: 11/23/2022]
Abstract
The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide, especially as a result of our aging society, high caloric intake and sedentary lifestyle. Besides the well-known complications of T2DM on the cardiovascular system, the eyes, kidneys and nerves, bone strength is also impaired in diabetic patients. Patients with T2DM have a 40-70% increased risk for fractures, despite having a normal to increased bone mineral density, suggesting that other factors besides bone quantity must account for increased bone fragility. This review summarizes the current knowledge on the complex effects of T2DM on bone including effects on bone cells, bone material properties and other endocrine systems that subsequently affect bone, discusses the effects of T2DM medications on bone and concludes with a model identifying factors that may contribute to poor bone quality and increased bone fragility in T2DM.
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Affiliation(s)
- Ann-Kristin Picke
- Institute of Comparative Molecular Endocrinology, Ulm University, Ulm, Germany
| | - Graeme Campbell
- Institute of Biomechanics, TUHH Hamburg University of Technology, Hamburg, Germany
| | - Nicola Napoli
- Diabetes and Bone Network, Department Endocrinology and Diabetes, University Campus Bio-Medico of Rome, Rome, Italy
- Division of Bone and Mineral Diseases, Washington University in St Louis, St Louis, Missouri, USA
| | - Lorenz C Hofbauer
- Department of Medicine III & Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
| | - Martina Rauner
- Department of Medicine III & Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
- Correspondence should be addressed to M Rauner:
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Feng W, Bi Y, Li P, Yin T, Gao C, Shen S, Gao L, Yang D, Zhu D. Effects of liraglutide, metformin and gliclazide on body composition in patients with both type 2 diabetes and non-alcoholic fatty liver disease: A randomized trial. J Diabetes Investig 2019; 10:399-407. [PMID: 29957886 PMCID: PMC6400178 DOI: 10.1111/jdi.12888] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 06/19/2018] [Accepted: 06/25/2018] [Indexed: 02/06/2023] Open
Abstract
AIMS/INTRODUCTION To compare the effects of gliclazide, liraglutide and metformin on body composition in patients with type 2 diabetes mellitus with non-alcoholic fatty liver disease. MATERIALS AND METHODS A total of 85 patients were randomly allocated to receive gliclazide (n = 27), liraglutide (n = 29) or metformin (n = 29) monotherapy for 24 weeks. Body composition was measured using dual-energy X-ray absorptiometry. RESULTS Liraglutide and metformin reduced total, trunk, limb, android and gynoid fat mass; this also led to weight reduction. However, gliclazide treatment produced no significant changes in weight or fat mass, likely because reductions in fat mass were concomitant with increases in lean tissue mass. Blood glucose concentrations and glycated hemoglobin levels improved in all treatment arms; levels of the latter were lower in patients treated with liraglutide and metformin. Serum alanine aminotransferase concentrations decreased in all treatment arms, whereas serum aspartate aminotransferase concentrations were reduced only by liraglutide and metformin. In all patients, weight loss and total, trunk, limb, and android fat mass reductions were positively correlated with decreases in serum alanine aminotransferase and aspartate aminotransferase levels, whereas reductions in waist circumference were positively correlated with lower serum alanine aminotransferase levels. CONCLUSIONS Compared with gliclazide, liraglutide and metformin monotherapies result in greater weight loss, reductions in body fat mass, and better blood glucose control among type 2 diabetes mellitus patients with non-alcoholic fatty liver disease. Reductions in weight, fat mass and waist circumference favorably affect hepatic function.
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Affiliation(s)
- Wen‐Huan Feng
- Department of EndocrinologyDrum Tower Hospital Affiliated to Nanjing University Medical SchoolNanjingChina
| | - Yan Bi
- Department of EndocrinologyDrum Tower Hospital Affiliated to Nanjing University Medical SchoolNanjingChina
| | - Ping Li
- Department of EndocrinologyDrum Tower Hospital Affiliated to Nanjing University Medical SchoolNanjingChina
| | - Ting‐Ting Yin
- Department of EndocrinologyDrum Tower Hospital Affiliated to Nanjing University Medical SchoolNanjingChina
- Medical School of Southeast UniversityNanjingChina
| | - Cai‐Xia Gao
- Department of Traditional Chinese MedicineYan'an People's HospitalYan'anChina
| | - Shan‐Mei Shen
- Department of EndocrinologyDrum Tower Hospital Affiliated to Nanjing University Medical SchoolNanjingChina
| | - Li‐Jun Gao
- Department of EndocrinologyDrum Tower Hospital Affiliated to Nanjing University Medical SchoolNanjingChina
- Medical School of Southeast UniversityNanjingChina
| | - Dong‐Hui Yang
- Department of EndocrinologyDrum Tower Hospital Affiliated to Nanjing University Medical SchoolNanjingChina
| | - Da‐Long Zhu
- Department of EndocrinologyDrum Tower Hospital Affiliated to Nanjing University Medical SchoolNanjingChina
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Mohan V, Cooper ME, Matthews DR, Khunti K. The Standard of Care in Type 2 Diabetes: Re-evaluating the Treatment Paradigm. Diabetes Ther 2019; 10:1-13. [PMID: 30758834 PMCID: PMC6408564 DOI: 10.1007/s13300-019-0573-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Indexed: 01/01/2023] Open
Abstract
There is currently a worldwide epidemic of type 2 diabetes (T2D) that is predicted to increase substantially in the next few years. With 80% of the global T2D population living in low to middle-income countries, there are issues with cost and of access to appropriate medicines. The objective of this symposium was to provide an overview of the efficacy and safety of glucose-lowering drugs, focussing in particular on sulfonylureas (SUs) in patients with T2D using data taken from both randomised controlled trials (RCTs) and real-world studies, the application of strategies to ensure optimal patient adherence and clinical outcomes, and the optimal use of SUs in terms of dose adjustment and agent choice to ensure the best clinical outcome. The symposium began by exploring a profile of the typical patient seen in diabetes clinical practice and the appropriate management of such a patient in the real world, before moving on to an overview of the risks associated with T2D and how the currently available agents, including newer antidiabetic medications, mitigate or exacerbate those risks. The final presentation provided an overview of real-world studies, the gap between RCTs and the real world, and the use of available glucose-lowering agents in daily clinical practice. Clinical evidence was presented demonstrating that tight glucose control improved both microvascular and macrovascular outcomes, but that aggressive treatment in patients with a very high cardiovascular risk could lead to adverse outcomes. Real-world data suggest that older agents such as SUs and metformin are being used in a large proportion of patients with T2D with demonstrable effectiveness, indicating that they still have a place in modern T2D management. The symposium, while acknowledging the need for newer antidiabetic drugs in specific situations and patient groups, recommended the continuation of SUs and metformin as the primary oral antidiabetic agents in resource-constrained regions of the world.Funding:Servier.
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Affiliation(s)
- Viswanathan Mohan
- Madras Diabetes Research Foundation and Dr Mohan's Diabetes Specialities Centre, Chennai, India.
| | - Mark E Cooper
- Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - David R Matthews
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, and Harris Manchester College, Oxford, UK
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester, UK
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Khunti K, Chatterjee S, Gerstein HC, Zoungas S, Davies MJ. Do sulphonylureas still have a place in clinical practice? Lancet Diabetes Endocrinol 2018; 6:821-832. [PMID: 29501322 DOI: 10.1016/s2213-8587(18)30025-1] [Citation(s) in RCA: 79] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 12/19/2017] [Accepted: 12/19/2017] [Indexed: 12/11/2022]
Abstract
Sulphonylureas have been commercially available since the 1950s, but their use continues to be associated with controversy. Although adverse cardiovascular outcomes in some observational studies have raised concerns about sulphonylureas, findings from relatively recent, robust, and high-quality systematic reviews have indicated no increased risk of all-cause mortality associated with sulphonylureas compared with other active treatments. Results from large, multicentre, randomised controlled trials such as the UK Prospective Diabetes Study and ADVANCE have confirmed the microvascular benefits of sulphonylureas, a reduction in the incidence or worsening of nephropathy and retinopathy, and no increase in all-cause mortality, although whether these benefits were due to sulphonylurea therapy and not an overall glucose-lowering effect could not be confirmed. A comparison of sulphonylureas and pioglitazone in the TOSCA.IT trial also confirmed the efficacy and cardiovascular safety of sulphonylureas. Investigators of randomised controlled trials have reported an increased risk of hypoglycaemia and weight gain with sulphonylureas, but data from observational studies suggest that the incidence of severe hypoglycaemia is lower in people taking sulphonylurea than in people taking insulin, and weight gain with sulphonylureas has been relatively modest in large cohort studies. 80% of people with diabetes live in low-to-middle income countries, so the effectiveness, affordability, and safety of sulphonylureas are particularly important considerations when prescribing glucose-lowering therapy. Results of ongoing head-to-head studies with new drugs, such as the comparison of glimepiride with linagliptin in the CAROLINA study and the comparison of various therapies (including sulphonylureas) for glycaemic control in the GRADE study, will determine the place of sulphonylureas in glucose-lowering therapy algorithms for patients with type 2 diabetes.
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Affiliation(s)
- Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK.
| | - Sudesna Chatterjee
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
| | - Hertzel C Gerstein
- Population Health Research Institute, McMaster University, ON, Canada; Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, McMaster University, ON, Canada
| | - Sophia Zoungas
- Division of Metabolism, Ageing and Genomics, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; The George Institute for Global Health, Sydney, NSW, Australia
| | - Melanie J Davies
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
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Starup-Linde J, Hygum K, Langdahl BL. Skeletal Fragility in Type 2 Diabetes Mellitus. Endocrinol Metab (Seoul) 2018; 33:339-351. [PMID: 30229573 PMCID: PMC6145952 DOI: 10.3803/enm.2018.33.3.339] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 08/22/2018] [Accepted: 08/29/2018] [Indexed: 12/16/2022] Open
Abstract
Type 2 diabetes (T2D) is associated with an increased risk of fracture, which has been reported in several epidemiological studies. However, bone mineral density in T2D is increased and underestimates the fracture risk. Common risk factors for fracture do not fully explain the increased fracture risk observed in patients with T2D. We propose that the pathogenesis of increased fracture risk in T2D is due to low bone turnover caused by osteocyte dysfunction resulting in bone microcracks and fractures. Increased levels of sclerostin may mediate the low bone turnover and may be a novel marker of increased fracture risk, although further research is needed. An impaired incretin response in T2D may also affect bone turnover. Accumulation of advanced glycosylation endproducts may also impair bone strength. Concerning antidiabetic medication, the glitazones are detrimental to bone health and associated with increased fracture risk, and the sulphonylureas may increase fracture risk by causing hypoglycemia. So far, the results on the effect of other antidiabetics are ambiguous. No specific guideline for the management of bone disease in T2D is available and current evidence on the effects of antiosteoporotic medication in T2D is sparse. The aim of this review is to collate current evidence of the pathogenesis, detection and treatment of diabetic bone disease.
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Affiliation(s)
- Jakob Starup-Linde
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark
| | - Katrine Hygum
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Bente Lomholt Langdahl
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
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Colagiuri S, Matthews D, Leiter LA, Chan SP, Sesti G, Marre M. The place of gliclazide MR in the evolving type 2 diabetes landscape: A comparison with other sulfonylureas and newer oral antihyperglycemic agents. Diabetes Res Clin Pract 2018; 143:1-14. [PMID: 29802958 DOI: 10.1016/j.diabres.2018.05.028] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Revised: 05/04/2018] [Accepted: 05/16/2018] [Indexed: 02/06/2023]
Abstract
The sulfonylureas are effective oral glucose-lowering agents with a long history of clinical use. While all have the same general mechanism of action, their pharmacokinetic properties are influenced by factors such as dosage, rate of absorption, duration of action, route of elimination, tissue specificity, and binding affinity for pancreatic β-cell receptor. The result is a class of agents with similar HbA1c-lowering efficacy, but well-documented differences in terms of effects on hypoglycemia, and cardiovascular and renal safety. This review examines the differences between currently available sulfonylureas with a focus on how gliclazide modified release (MR) differs from other members of this class and from newer oral antihyperglycemic agents in the form of dipeptidyl peptidase-4 (DPP4) and sodium- glucose cotransporter 2 (SGLT2) inhibitors. The first part focuses on major outcome trials that have been conducted with the sulfonylureas and new oral agents. Consideration is then given to factors important for day-to-day prescribing including efficacy and durability, weight changes, hypoglycemia, renal effects and cost. Based on current evidence, third-generation sulfonylureas such as gliclazide MR possess many of the properties desired of a type 2 diabetes drug including high glucose-lowering efficacy, once-daily oral administration, few side effects other than mild hypoglycemia, and cardiovascular safety.
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Affiliation(s)
- Stephen Colagiuri
- Boden Institute of Obesity, Nutrition and Exercise, University of Sydney, Sydney, NSW, Australia.
| | - David Matthews
- Oxford Centre for Diabetes, Endocrinology and Metabolism, and Harris Manchester College, University of Oxford, Oxford, UK
| | - Lawrence A Leiter
- Division of Endocrinology & Metabolism, Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Ontario, Canada
| | - Siew Pheng Chan
- Department of Medicine, University of Malaya Medical Centre, Kuala Lumpur 50603, W.P., Malaysia
| | - Giorgio Sesti
- Department of Medical and Surgical Science, University Magna-Græcia of Catanzaro, 88100 Catanzaro, Italy
| | - Michel Marre
- Diabetes Department, Hôpital Bichat-Claude Bernard, Assistance Publique des Hôpitaux de Paris, Université Denis Diderot Paris 7, and INSERM U1138, Paris, France
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Czyrski A, Resztak M, Hermann T. Determination of gliclazide minimum concentration in type 2 diabetes mellitus patients. Biomed Pharmacother 2018; 106:1267-1270. [PMID: 30119196 DOI: 10.1016/j.biopha.2018.07.078] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Revised: 07/02/2018] [Accepted: 07/14/2018] [Indexed: 12/12/2022] Open
Abstract
Type 2 diabetes mellitus is a worldwide health problem. Many drugs can be used in its treatment. One of them is gliclazide - the sulfonylurea derivative. It is dosed in modified release tablets. The study aimed to determine the minimum steady-state concentration of gliclazide at patients taking modified release tablets. Fasting plasma glucose, insulin level, and glycated hemoglobin were also assayed in this study. Ten patients of the primary care physician clinic took 30-90 mg of gliclazide daily. The statistical analysis proved that there is a statistically significant correlation between insulin level and body weight (p = 0.044) as well as between the dose and gliclazide concentrations (p = 0.015) and also between insulin level and minimum concentration of the drug (p = 0.0074). The linear correlation between dose and gliclazide's minimum steady state concentration proved its linear pharmacokinetics. The correlation between the minimum concentration of gliclazide and insulin level might be a potential predictor of patients compliance.
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Affiliation(s)
- Andrzej Czyrski
- Department of Physical Pharmacy and Pharmacokinetics, Poznań University of Medical Sciences, 6 Święcickiego Street, 60-781 Poznań, Poland.
| | - Matylda Resztak
- Department of Physical Pharmacy and Pharmacokinetics, Poznań University of Medical Sciences, 6 Święcickiego Street, 60-781 Poznań, Poland
| | - Tadeusz Hermann
- Department of Physical Pharmacy and Pharmacokinetics, Poznań University of Medical Sciences, 6 Święcickiego Street, 60-781 Poznań, Poland
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Landman GWD, Kleefstra N, van Hateren KJJ. Residual confounding in the study by van Dalem et al. Diabetes Obes Metab 2018; 20:1547-1548. [PMID: 29493108 DOI: 10.1111/dom.13269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 02/24/2018] [Accepted: 02/26/2018] [Indexed: 11/27/2022]
Affiliation(s)
- Gijs W D Landman
- Internal Medicine, Gelre Ziekenhuizen, Apeldoorn, the Netherlands
| | - Nanne Kleefstra
- Research Department, Langerhans Medical Research Group, Ommen, the Netherlands
- Internal Medicine, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
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Kunjiappan S, Panneerselvam T, Prasad P, Sukumaran S, Somasundaram B, Sankaranarayanan M, Murugan I, Parasuraman P. Design, graph theoretical analysis and
in silico
modeling of
Dunaliella bardawil
biomass encapsulated keratin nanoparticles: a scaffold for effective glucose utilization. Biomed Mater 2018; 13:045012. [DOI: 10.1088/1748-605x/aabcea] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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49
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Lanning MS, Carmody D, Szczerbiński Ł, Letourneau LR, Naylor RN, Greeley SAW. Hypoglycemia in sulfonylurea-treated KCNJ11-neonatal diabetes: Mild-moderate symptomatic episodes occur infrequently but none involving unconsciousness or seizures. Pediatr Diabetes 2018; 19:393-397. [PMID: 29205704 PMCID: PMC5918230 DOI: 10.1111/pedi.12599] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Revised: 09/20/2017] [Accepted: 09/22/2017] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Neonatal diabetes mellitus (NDM) caused by mutations in KCNJ11 can be successfully treated with high dose oral sulfonylureas; however, little data is available on the risk of hypoglycemia. OBJECTIVE To determine the frequency, severity, and clinical significance of hypoglycemia in KCNJ11-related NDM. METHODS Utilizing the University of Chicago Monogenic Diabetes Registry, parents completed an online questionnaire addressing hypoglycemia. Continuous glucose monitoring (CGM) data was available for 7 subjects. RESULTS Thirty subjects with KCNJ11-related permanent NDM (166 patient-years on sulfonylurea) had median sulfonylurea dose of 0.39 mg/kg/day (0.24-0.88 IQR, interquartile range) with median HbA1c 5.7% (39 mmol/mol) (5.5-6.1 IQR, 37-43 mmol/mol). Hypoglycemia (<70 mg/dL) was reported monthly once or less frequently in 89.3% of individuals, but 3 (10.7%) reported once weekly or more. Of all hypoglycemic episodes reported, none involved seizures or unconsciousness and thus did not meet the current ISPAD definition of severe hypoglycemia. Seven individuals wore a CGM for a total of 912 hours with blood sugars falling below 70 mg/dL for 5.8% of the time recorded, similar to ranges reported for people without diabetes. CONCLUSIONS In our cohort of KCNJ11-related permanent NDM, hypoglycemia is infrequent and mild despite the high doses of sulfonylurea used and near-normal level of glycemic control. Long-term follow-up on larger numbers will be required to clarify the incidence and determinants of hypoglycemia in this unique population.
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Affiliation(s)
- Monica S Lanning
- Section of Adult and Pediatric Endocrinology, Diabetes, & Metabolism, Departments of Medicine and Pediatrics, The University of Chicago, Chicago, Illinois
| | - David Carmody
- Section of Adult and Pediatric Endocrinology, Diabetes, & Metabolism, Departments of Medicine and Pediatrics, The University of Chicago, Chicago, Illinois
| | | | - Lisa R Letourneau
- Section of Adult and Pediatric Endocrinology, Diabetes, & Metabolism, Departments of Medicine and Pediatrics, The University of Chicago, Chicago, Illinois
| | - Rochelle N Naylor
- Section of Adult and Pediatric Endocrinology, Diabetes, & Metabolism, Departments of Medicine and Pediatrics, The University of Chicago, Chicago, Illinois
| | - Siri Atma W Greeley
- Section of Adult and Pediatric Endocrinology, Diabetes, & Metabolism, Departments of Medicine and Pediatrics, The University of Chicago, Chicago, Illinois
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Digenio A, Pham NC, Watts LM, Morgan ES, Jung SW, Baker BF, Geary RS, Bhanot S. Antisense Inhibition of Protein Tyrosine Phosphatase 1B With IONIS-PTP-1B Rx Improves Insulin Sensitivity and Reduces Weight in Overweight Patients With Type 2 Diabetes. Diabetes Care 2018; 41:807-814. [PMID: 29439147 DOI: 10.2337/dc17-2132] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 01/17/2018] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To evaluate safety and efficacy of IONIS-PTP-1BRx, a second-generation 2'-O-methoxyethyl antisense inhibitor of protein tyrosine phosphatase 1B, as add-on therapy in overweight patients with type 2 diabetes inadequately controlled with metformin with or without sulfonylurea therapy. RESEARCH DESIGN AND METHODS In this phase II, double-blind, randomized, placebo-controlled, multicenter trial, overweight and obese patients (BMI ≥27 kg/m2) with type 2 diabetes (HbA1c ≥7.5% [58 mmol/mol] and ≤10.5% [91 mmol/mol]) on a stable dose of metformin alone or with sulfonylurea were randomized 2:1 to IONIS-PTP-1BRx 200 mg (n = 62) or placebo (n = 30) once weekly for 26 weeks. RESULTS Mean baseline HbA1c was 8.6% (70 mmol/mol) and 8.7% (72 mmol/mol) in placebo and active treatment, respectively. At week 27, IONIS-PTP-1BRx reduced mean HbA1c levels by -0.44% (-4.8 mmol/mol; P = 0.074) from baseline and improved leptin (-4.4 ng/mL; P = 0.007) and adiponectin (0.99 μg/mL; P = 0.026) levels compared with placebo. By week 36, mean HbA1c was significantly reduced (-0.69% [-7.5 mmol/mol]; P = 0.034) and accompanied by reductions in fructosamine (-33.2 μmol/L; P = 0.005) and glycated albumin (-1.6%; P = 0.031) versus placebo. Despite both treatment groups receiving similar lifestyle counseling, mean body weight significantly decreased from baseline to week 27 with IONIS-PTP-1BRx versus placebo (-2.6 kg; P = 0.002) independent of HbA1c reduction (R2 = 0.0020). No safety concerns were identified in the study. CONCLUSIONS Compared with placebo, IONIS-PTP-1BRx treatment for 26 weeks produced prolonged reductions in HbA1c, improved medium-term glycemic parameters, reduced leptin and increased adiponectin levels, and resulted in a distinct body weight-reducing effect.
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