Update on Cardiovascular Safety of Incretin-Based Therapy in Adults With Type 2 Diabetes Mellitus: A Meta-Analysis of Cardiovascular Outcome Trials

Abstract

The authors of 2 large randomized trials have recently published their findings related to the effects of a glucagon-like peptide 1 receptor agonist (GLP-1RA) (the HARMONY trial) and a dipeptidyl peptidase 4 (DPP-4) inhibitor (the CARMELINA trial) on cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus. In light of these new data, we conducted a systematic review and meta-analysis of GLP-1RAs and DPP-4 inhibitors in CV outcome trials to assess their CV safety in patients with type 2 diabetes. We conducted a comprehensive literature search in the Embase and MEDLINE databases to identify trials involving GLP-1RAs and DPP-4 inhibitors with major CV-related outcomes reported, including major adverse CV events, CV death, myocardial infarction, stroke, death from any cause and hospitalization because of heart failure. A total of 9 CV outcome trials were included. Odds ratios and 95% confidence intervals were calculated based on the Mantel-Haenszel method. Relative to placebo, GLP-1RAs were associated with a statistically significant reduction in the odds of major adverse CV events (13%), CV death (12%), death from any cause (11%) and stroke (13%). DPP-4 inhibitors were comparable to placebo for all outcomes. Moreover, DPP-4 inhibitors were associated with a nonsignificant 5% increase in the odds of hospitalization from heart failure compared to placebo. This meta-analysis demonstrated that GLP-1RAs were associated with a significant reduction in major adverse CV events, CV death, stroke and death from any cause, while DPP-4 inhibitors were comparable to placebo for all CV outcomes, including hospitalizations for heart failure.