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.