Effect of Anti-diabetic Drugs on Cardiovascular Mortality And Heart Failure Hospitalizations: A Meta-analysis Study

Introduction Diabetes mellitus is associated with worse cardiovascular outcomes. Unlike previous anti-diabetic medications, recent clinical trials of glucagon-like peptide-1 receptor agonists(GLP-1 RAs) and sodium glucose co-transporter-2 (SGLT-2) inhibitors were shown to reduce cardiovascular events. However, it is not known if all new anti-diabetic medications have cardiovascular benefit. We therefore conducted a meta-analysis to determine the effect of GLP-1 RAs, SGLT-2, dipeptidyl peptidase-4 (DPP-4) inhibitors which are major recent new anti-diabetics on cardiovascular outcomes. Methods MEDLINE/PubMed, EMBASE, SCOPUS and Cochrane database were searched for pertinent studies. We included cardiovascular outcome trials reporting cardiovascular outcomes in GLP1 RAs, SGLT2 and DPP4 inhibitors. We looked at the outcomes of cardiovascular mortality and Heart failure (HF) hospitalization. Random effects model was used to perform the meta-analysis. Results A total of 18 trials with 157,730 patients were included. SGLT-2 inhibitors showed reduced cardiovascular mortality and HF hospitalizations compared to placebo (HR 0.83 95% CI 0.76 - 0.90 and HR 0.68 95% CI 0.62 - 0.75). GLP1 RAs reduced cardiovascular mortality and HF hospitalizations compared to placebo. (HR 0.88 95% CI 0.81 - 0.95 and HR 0.91 95% CI 0.84 - 0.99). DPP-4 inhibitors were associated with higher risks of cardiovascular mortality (HR 0.99 95% CI (0.91 - 1.08) and HF hospitalizations (HR 1.08 95% CI 0.98 - 1.18) compared to placebo. Rank graph meta-analysis showed SGLT-2 inhibitors showed more reduction in cardiovascular mortality and HF hospitalizations than GLP-1 RAs Conclusion SGLT-2 inhibitors are superior in reducing cardiovascular mortality and HF hospitalizations among new antidiabetic drug class whereas DPP-4 inhibitors are associated with worse cardiovascular outcomes.