Cardiovascular outcomes of sodium glucose cotransporter-2 inhibitors in patients with type 2 diabetes

Aims To determine the association between cardiovascular diseases (CVD) and SGLT2 inhibitors compared to sulfonylureas and dipeptidyl peptidase-4 (DPP4) inhibitors and to examine within-class effects of SGLT2 inhibitors. Methods A retrospective cohort analysis was conducted using Truven Health MarketScan. New users of SGLT2 inhibitors, sulfonylureas or DPP-4 inhibitors were included. Primary outcome was incident CVD, defined as non-fatal myocardial infarction or non-fatal stroke; secondary outcomes were hospitalization because of heart failure and lower extremity amputation. Proportional hazards models, after propensity score matching, were used to obtain hazard ratios (HR) and 95% confidence intervals (CI). Results In fully adjusted models, use of SGLT2 inhibitors was associated with a decreased risk of developing CVD compared with use of sulfonylureas (HR, 0.50; 95% CI, 0.45, 0.55) and DPP-4 inhibitors (HR, 0.57; 95% CI, 0.52, 0.62), respectively. Analyses revealed no evidence of within-class effects: dapagliflozin vs sulfonylureas (HR, 0.55; 95% CI, 0.43, 0.70) or DPP-4 inhibitors (HR, 0.57; 95% CI, 0.46, 0.70); and canagliflozin vs sulfonylureas (HR, 0.61; 95% CI, 0.54, 0.69) or DPP-4 inhibitors (HR, 0.66; 95% CI, 0.54, 0.71). Additionally, SGLT2 inhibitors were associated with lower risk of hospitalization because of heart failure compared to both sulfonylureas and DPP-4 inhibitors, as well as lower risk of lower extremity amputation compared to sulfonylureas. Conclusion Using population-based data, incident use of SGLT-2 inhibitors was associated with a decreased incidence of CVD compared to use of sulfonylureas and DPP-4 inhibitors. These findings were consistent between dapagliflozin and canagliflozin, suggesting that CVD reduction is a class effect for SGLT2 inhibitors. In addition, SGLT2 inhibitors portended lower risk of hospitalization because of heart failure (vs sulfonylureas and DPP-4 inhibitors) and lower risk of lower extremity amputation (vs sulfonylureas).