Comparative Efficacy of Five SGLT2i on Cardiorenal Events: A Network Meta-analysis Based on Ten CVOTs

Abstract

Background: The relative efficacy of different sodium-glucose transporter 2 inhibitors (SGLT2i) on cardiorenal outcomes is unclear.

Methods: We included cardiovascular outcome trials (CVOTs) of SGLT2i. The eight endpoints of interest were major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, cardiovascular death (CVD), CVD or hospitalization for heart failure (HHF), HHF, kidney function progression (KFP), and all-cause death (ACD). We conducted a Bayesian network meta-analysis and calculated the surface under the cumulative ranking curve (SUCRA) probability to rank treatments.

Results: We included ten CVOTs involving five SGLT2i. Canagliflozin (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.53-0.77), dapagliflozin (HR 0.70; 95% CI 0.62-0.79), empagliflozin (HR 0.68; 95% CI 0.59-0.78), ertugliflozin (HR 0.70; 95% CI 0.54-0.90), and sotagliflozin (HR 0.66; 95% CI 0.56-0.77) versus placebo reduced HHF, whereas none reduced MI and stroke. Empagliflozin reduced CVD or HHF (HR 0.81; 95% CI 0.67-0.99) and KFP (HR 0.65; 95% CI 0.45-0.93), and dapagliflozin reduced KFP (HR 0.69; 95% CI 0.52-0.92), versus ertugliflozin. Canagliflozin had the greatest SUCRA values for the reduction of MACE, stroke, and HHF, whereas empagliflozin had the greatest SUCRA values for the reduction of MI, CVD, CVD or HHF, KFP, and ACD.

Conclusions: Canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin versus placebo reduce HHF but none reduces MI and stroke. Canagliflozin is most effective in reducing MACE and HHF, and empagliflozin is most effective in reducing CVD, CVD or HHF, KFP, and ACD. These findings will guide the use of specific SGLT2i in the prevention of different cardiorenal events.