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.