Canagliflozin reduced heart failure hospitalization by 52% (HR 0.48), Semaglutide lowered all-cause mortality risk (HR 0.81), and Efpeglenatide reduced cardiovascular mortality (HR 0.76) in T2DM.
Do GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors reduce cardiovascular events and mortality in patients with type 2 diabetes compared to placebo?
This network meta-analysis demonstrates differential cardiovascular benefits among diabetes drug classes, with canagliflozin ranking highest for preventing heart failure hospitalizations, and semaglutide/efpeglenatide ranking highest for reducing mortality.
Absolute Event Rate: 0% vs 0%
Abstract Background GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors are widely utilized in type 2 diabetes management, with emerging evidence suggesting their differential impact on cardiovascular outcomes. This Bayesian network meta-analysis systematically evaluates and ranks their effectiveness in reducing cardiovascular events, providing a robust comparative assessment for optimizing therapeutic strategies. Purpose To compare the effectiveness of GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors on cardiovascular outcomes, including hospitalization for heart failure (HHF), all-cause mortality, and cardiovascular mortality. Methods A systematic search was conducted in PubMed, Embase, and Scopus to identify randomized controlled trials (RCTs) evaluating GLP-1 receptor agonists (GLP-1 RAs), DPP-4 inhibitors, and SGLT-2 inhibitors, compared to placebo in patients with type 2 diabetes. Hazard ratios (HR) with 95% credible intervals (CrI) were estimated for time-to-event outcomes. A random-effects Bayesian model was used, and Surface Under the Cumulative Ranking Curve (SUCRA) values were calculated to rank interventions. Bayesian inference was conducted using Markov Chain Monte Carlo (MCMC) simulations. Data was extracted after fitting the model with Deviance Information Criterion (DIC) diagnostics and posterior density estimates (Dres) after appropriate iterations when Potential Scale Reduction Factor (PSRF) approached 1, ensuring model convergence. Results We analyzed data from 30 randomized controlled trials (RCTs) involving 226,557 patients to assess cardiovascular outcomes in individuals with type 2 diabetes. For heart failure hospitalization (HHF), Canagliflozin was ranked as the most effective (HR: 0.48, 95% CrI: 0.37 to 0.61; SUCRA: 97.45%), followed by Sotagliflozin (HR: 0.63, 95% CrI: 0.51 to 0.77; SUCRA: 84.44%) and Omarigliptin (HR: 0.63, 95% CrI: 0.32 to 1.08; SUCRA: 79.44%), compared to Placebo (SUCRA: 21.85%). For all-cause mortality, Semaglutide had the lowest associated risk (HR: 0.81, 95% CrI: 0.62 to 1.01; SUCRA: 78.11%), followed by Efpeglenatide (HR: 0.82, 95% CrI: 0.53 to 1.23; SUCRA: 72.26%) and Canagliflozin (HR: 0.85, 95% CrI: 0.66 to 1.09; SUCRA: 68.35%), compared to Placebo (SUCRA: 31.56%). For cardiovascular mortality, Efpeglenatide was the most effective (HR: 0.76, 95% CrI: 0.49 to 1.14; SUCRA: 78.82%), followed by Liraglutide (HR: 0.79, 95% CrI: 0.58 to 1.05; SUCRA: 77.44%) and Empagliflozin (HR: 0.81, 95% CrI: 0.68 to 0.94; SUCRA: 75.48%), compared to Placebo (SUCRA: 26.98%). Conclusion This study highlights the superior effectiveness of Canagliflozin in reducing heart failure hospitalization, while Semaglutide and Efpeglenatide show the most significant reductions in all-cause and cardiovascular mortality, respectively. These findings underscore the importance of individualized treatment strategies in managing cardiovascular outcomes in patients with type 2 diabetes.League table of HF hospitalization Forest plot of mortality outcomes
Khalil et al. (Sat,) reported a other. Canagliflozin reduced heart failure hospitalization by 52% (HR 0.48), Semaglutide lowered all-cause mortality risk (HR 0.81), and Efpeglenatide reduced cardiovascular mortality (HR 0.76) in T2DM.