Obesity as a modifier of the cardiovascular effectiveness of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes

Aims To assess the association between the use of sodium-glucose cotransporter-2 (SGLT2i) and cardiovascular outcomes and death as a function of obesity among patients with type 2 diabetes. Methods This new-user, active-comparator cohort study used U.K.’s Clinical Practice Research Datalink linked to Hospital Episodes Statistics repository and Office for National Statistics. The cohort included 34,128 new-users of SGLT2i matched 1:1 to 34,128 new-users of dipeptidyl peptidase-4 inhibitors (DPP-4i) on body mass index and propensity score. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of major adverse cardiovascular events (MACE), overall and in body mass index (BMI) categories (≤24.9 kg/m2, 25.0–29.9 kg/m2, 30.0–39.9 kg/m2, ≥40 kg/m2). Secondary outcomes included all-cause mortality and hospitalization for heart failure. Results SGLT2i were associated with a decreased risk of MACE (HR: 0.78, 95 %CI: 0.69–0.88) compared to DPP-4i. This decreased risk was most pronounced among obese and severely obese patients (HR: 0.77, 95 %CI: 0.66–0.91; HR: 0.67, 95% CI: 0.49–0.91, respectively) but not among overweight patients (HR: 0.94, 95 %CI: 0.73–1.22). Similar patterns were observed for cardiovascular mortality, all-cause mortality, and heart failure. Conclusion Compared with DPP-4i, the cardioprotective effect associated with SGLT2i is stronger among patients with higher BMI.