Antonios Douros1,2,3, Hui Yin1, Oriana Hoi Yun Yu1,4, Kristian B Filion1,2,5, Laurent Azoulay1,2,6, Samy Suissa7,2,5. 1. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. 2. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada. 3. Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Berlin, Germany. 4. Division of Endocrinology, Jewish General Hospital, Montreal, Quebec, Canada. 5. Division of Clinical Epidemiology, Department of Medicine, McGill University, Montreal, Quebec, Canada. 6. Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada. 7. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada samy.suissa@mcgill.ca.
Abstract
OBJECTIVE: Sulfonylureas have been associated with an increased risk of cardiovascular adverse events and hypoglycemia, but it is unclear if these risks vary with different agents. We assessed whether the risks of acute myocardial infarction, ischemic stroke, cardiovascular death, all-cause mortality, and severe hypoglycemia differ between sulfonylureas grouped according to pancreas specificity and duration of action. RESEARCH DESIGN AND METHODS: Using the U.K. Clinical Practice Research Datalink, linked with the Hospital Episodes Statistics and the Office for National Statistics databases, we conducted a cohort study among patients with type 2 diabetes initiating monotherapy with sulfonylureas between 1998 and 2013. Adjusted hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, comparing use of pancreas-nonspecific, long-acting sulfonylureas (glyburide/glimepiride) to pancreas-specific, short-acting sulfonylureas (gliclazide/glipizide/tolbutamide). RESULTS: The cohort included 17,604 sulfonylurea initiators (mean [SD] follow-up 1.2 [1.5] years). Compared with specific, short-acting sulfonylureas (15,741 initiators), nonspecific, long-acting sulfonylureas (1,863 initiators) were not associated with an increased risk of acute myocardial infarction (HR 0.86; CI 0.55-1.34), ischemic stroke (HR 0.92; CI 0.59-1.45), cardiovascular death (HR 1.01; CI 0.72-1.40), or all-cause mortality (HR 0.81; CI 0.66-1.003), but with an increased risk of severe hypoglycemia (HR 2.83; CI 1.64-4.88). CONCLUSIONS: The nonspecific, long-acting sulfonylureas glyburide and glimepiride do not have an increased risk of cardiovascular adverse events compared with the specific, short-acting sulfonylureas gliclazide, glipizide, and tolbutamide. However, nonspecific, long-acting sulfonylureas glyburide and glimepiride have an increased risk of severe hypoglycemia.
OBJECTIVE:Sulfonylureas have been associated with an increased risk of cardiovascular adverse events and hypoglycemia, but it is unclear if these risks vary with different agents. We assessed whether the risks of acute myocardial infarction, ischemic stroke, cardiovascular death, all-cause mortality, and severe hypoglycemia differ between sulfonylureas grouped according to pancreas specificity and duration of action. RESEARCH DESIGN AND METHODS: Using the U.K. Clinical Practice Research Datalink, linked with the Hospital Episodes Statistics and the Office for National Statistics databases, we conducted a cohort study among patients with type 2 diabetes initiating monotherapy with sulfonylureas between 1998 and 2013. Adjusted hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, comparing use of pancreas-nonspecific, long-acting sulfonylureas (glyburide/glimepiride) to pancreas-specific, short-acting sulfonylureas (gliclazide/glipizide/tolbutamide). RESULTS: The cohort included 17,604 sulfonylurea initiators (mean [SD] follow-up 1.2 [1.5] years). Compared with specific, short-acting sulfonylureas (15,741 initiators), nonspecific, long-acting sulfonylureas (1,863 initiators) were not associated with an increased risk of acute myocardial infarction (HR 0.86; CI 0.55-1.34), ischemic stroke (HR 0.92; CI 0.59-1.45), cardiovascular death (HR 1.01; CI 0.72-1.40), or all-cause mortality (HR 0.81; CI 0.66-1.003), but with an increased risk of severe hypoglycemia (HR 2.83; CI 1.64-4.88). CONCLUSIONS: The nonspecific, long-acting sulfonylureasglyburide and glimepiride do not have an increased risk of cardiovascular adverse events compared with the specific, short-acting sulfonylureasgliclazide, glipizide, and tolbutamide. However, nonspecific, long-acting sulfonylureasglyburide and glimepiride have an increased risk of severe hypoglycemia.
Authors: Sridharan Raghavan; Wenhui G Liu; David R Saxon; Gary K Grunwald; Thomas M Maddox; Jane E B Reusch; Seth A Berkowitz; Liron Caplan Journal: BMJ Open Diabetes Res Care Date: 2018-06-15
Authors: Viswanathan Mohan; Kamlesh Khunti; Siew P Chan; Fadlo F Filho; Nam Q Tran; Kaushik Ramaiya; Shashank Joshi; Ambrish Mithal; Maïmouna N Mbaye; Nemencio A Nicodemus; Tint S Latt; Linong Ji; Ibrahim N Elebrashy; Jean C Mbanya Journal: Diabetes Ther Date: 2019-11-26 Impact factor: 2.945