The modifying effects of adiposity on the cardiovascular safety of sulphonylureas

Abstract

Aims: To determine whether adiposity modified the effect on the cardiovascular safety of sulphonylureas 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 sulphonylurea 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 [MI], ischaemic stroke, cardiovascular mortality), and all-cause mortality, comparing use of sulphonylureas with use of metformin, overall and within BMI categories (≤24.9 kg/m2, 25.0-29.9 kg/m2, ≥30 kg/m2). Results: Compared with metformin, sulphonylureas were not associated with an increased risk of MACE either overall (HR 1.08, 95% CI 0.94-1.23) or by BMI category. Similar findings were observed for MI and ischaemic stroke. By contrast, sulphonylureas 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 sulphonylureas and cardiovascular and all-cause mortality compared with metformin.