Glucagon-like peptide-1 receptor agonists and cardiovascular outcomes in patients with and without prior cardiovascular events: An updated meta-analysis and subgroup analysis of randomized controlled trials

Aim: To conduct a meta-analysis of cardiovascular outcome trials on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major adverse cardiovascular events (MACE). Methods: A search of MEDLINE, EMBASE, Cochrane database and clinicaltrials.gov was performed to identify controlled trials (up to 15 June 2019) of GLP-1RAs with a cardiovascular endpoint. The principal endpoint of the present meta-analysis was MACE; secondary endpoints included myocardial infarction, stroke, cardiovascular and all-cause mortality, and hospitalization for heart failure. Mantel–Haenszel odds ratios (MH-ORs) with 95% confidence intervals (CIs) were calculated for all outcomes. Results: In the seven trials included, all placebo-controlled, GLP-1RA treatment was associated with a reduction in MACE (MH-OR 0.87 [95% CI 0.81, 0.93]). Cardiovascular and all-cause mortality, myocardial infarction and stroke were also reduced (MH-OR 0.88 [95% CI 0.80, 0.96], MH-OR 0.90 [95% CI 0.82, 0.98], MH-OR 0.91 [95% CI 0.84, 0.98] and MH-OR 0.86 [95% CI 0.77, 0.97], respectively). Results for hospitalization for heart failure were not statistically significant (MH-OR 0.93 [95% CI 0.83, 1.04]). The meta-analyses of patient subgroups showed a significant reduction in MACE with GLP-1RAs, irrespective of gender, advanced age and obesity. Conclusions: GLP-1RAs are associated with a reduction in cardiovascular morbidity and mortality in high-risk patients with diabetes. This effect does not appear to be moderated by gender or body mass index. The possibility of different effects of GLP-1RAs between patients in primary and secondary prevention merits further investigation.