The Modifying Effects of Adiposity on the Cardiovascular Safety of Sulfonylureas.
AIMS: To determine whether adiposity modified the effect on the cardiovascular safety of sulfonylureas as a first-line therapy compared with metformin among patients with type 2 diabetes.
MATERIALS AND METHODS: Using the UK Clinical Practice Research Datalink, we conducted a cohort study among 13 862 new sulfonylurea users matched on body mass index (BMI) and propensity score, in a 1:1 ratio, to new metformin users between April 1, 1998 and December 31, 2016. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of major adverse cardiovascular events (MACE), individual components of MACE (myocardial infarction, ischemic stroke, cardiovascular mortality), and all-cause mortality, comparing use of sulfonylureas with use of metformin overall, and within BMI categories (</= 24.9 kg/m(2) , 25.0-29.9 kg/m(2) , >/= 30 kg/m(2) ).
RESULTS: Compared with metformin, sulfonylureas were not associated with an increased risk of MACE either overall (HR: 1.08; 95% CI: 0.94-1.23) or by BMI categories. Similar findings were observed for myocardial infarction and ischemic stroke. In contrast, sulfonylureas were associated with an increased risk of cardiovascular mortality (HR: 1.24; 95% CI: 1.04-1.48), primarily among obese patients (HR: 1.52; 95% CI: 1.08-2.13), and not among normal-weight patients (HR: 1.00; 95% CI: 0.72-1.39; p-interaction: 0.21). Similar results were observed for all-cause mortality (HR: 1.47; 95% CI: 1.32-1.62), where an increased risk was observed among obese patients (HR: 1.83; 95% CI: 1.49-2.25), but not normal-weight patients (HR: 1.18; 95% CI: 0.99-1.42; p-interaction: 0.006).
CONCLUSION: The findings of this study suggest that adiposity may have a modifying effect on the association between sulfonylureas and cardiovascular and all-cause mortality compared with metformin. This article is protected by copyright. All rights reserved.
|投稿者||Suissa, Karine; Schneeweiss, Sebastian; Douros, Antonios; Filion, Kristian B; Yin, Hui; Patorno, Elisabetta; Azoulay, Laurent|
|ジャーナル名||Diabetes, obesity & metabolism|
|組織名||Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine,;Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts,;United States.;Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital,;Montreal, Canada.;Department of Epidemiology, Biostatistics, and Occupational Health, McGill;University, Montreal, Canada.;Department of Medicine, McGill University, Montreal, Canada.;Institute of Clinical Pharmacology and Toxicology, Charite - Universitatsmedizin;Berlin, Berlin, Germany.;Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada.|