Effects of exenatide long-acting release on cardiovascular events and mortality in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

Aims Patients with type 2 diabetes (T2D) have an increased risk of cardiovascular disease. Recent cardiovascular outcome trials (CVOTs) with liraglutide, semaglutide, and albiglutide have shown significant reduction in major adverse cardiovascular events. Conversely, the CVOT with exenatide long-acting release (ELAR) confirmed cardiovascular safety of the drug, but did not reached superiority versus placebo. Herein, we systematically evaluated the effect of ELAR versus placebo or active comparators on cardiovascular events and mortality in patients with T2D. Methods We screened the literature for randomized controlled trials reporting cardiovascular events and deaths in patients receiving ELAR versus those receiving placebo or any other glucose-lowering medications. Event rates were pooled and compared using the random-effects model. Result We retrieved 16 trials comparing the occurrence of cardiovascular events and mortality in patients treated with ELAR versus placebo or active comparators. The pooled rate ratio for cardiovascular events was similar in the two groups (0.99; 95% CI 0.92–1.06). The rate ratio for all-cause mortality was significantly lower in exenatide group than in comparators (0.87; 95% CI 0.77–0.97). When results of the EXSCEL trial were omitted, the pooled rate ratio for cardiovascular events and mortality was 0.80 (95% CI 0.40–1.63) and 0.75 (95% CI 0.30–1.84), respectively. Conclusions Treatment with ELAR does not increase the risk of cardiovascular events and may reduce all-cause mortality.