Glucagon-like Peptide-1 Receptor Agonists and Cardioprotective Benefit in Patients with Type 2 Diabetes Without Baseline Metformin: A Systematic Review and Update Meta-analysis

Abstract

Sodium Glucose Co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) were associated with a reduction in cardiovascular disease events in cardiovascular outcomes trials (CVOTs) in type 2 diabetes. Most of the patients included in these trials received metformin as background therapy. To evaluate the effect of glucagon-like peptide 1 receptor agonists on major cardiovascular events (MACE) and mortality in metformin-naïve patients with type 2 diabetes. A systematic review and meta-analysis of randomized controlled clinical trials of GLP-1RAs on type 2 diabetes population was performed, after searching the PubMed/MEDLINE, Embase, Scielo, Google Scholar and Cochrane Controlled Trials databases. The primary endpoint was MACE. The secondary endpoints were cardiovascular death and all-cause mortality. A meta-analysis of time-to-event outcomes was performed. This meta-analysis was registered in PROSPERO (CRD42021260040) Seven trials, including 11510 patients, were identified and considered eligible for the analyses. GLP-1RAs were associated with a significant reduction in MACE incidence (HR: 0.86, 95% confidence interval: 0.79–0.94; I2: 0%). The secondary endpoints analysis showed a non-significant reduction in all-cause mortality (HR: 0.86, 95% confidence interval: 0.73–1.00 I2: 0%) and cardiovascular mortality (HR: 0.81, 95% confidence interval: 0.63–1.05; I2: 0%). In this meta-analysis, GLP-1RAs reduced the incidence of MACE in patients with type 2 diabetes without metformin at baseline, without significant reduction in all-cause mortality and cardiovascular mortality. These results support the fact that when a GLP-1RAs is administered, the benefit on cardiovascular outcomes is independent of the use of metformin.