Glucagon-like Peptide-1 Receptor Agonists and Cardioprotective Benefit in Patients With Type 2 Diabetes Without Baseline Metformin: An Update Meta-analysis

Abstract Background: Sodium Glucose Co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) were associated with a reduction in cardiovascular events in cardiovascular outcomes trials (CVOTs) in type 2 diabetes. Most of the patients included in these trials received metformin as background therapy. The purpose of this study was to evaluate the effect of glucagon-like peptide-1 receptor agonists on major cardiovascular events (MACE) in metformin-naïve patients with type 2 diabetes.Methods: A meta-analysis was performed of randomized controlled clinical trials of GLP-1RAs on type 2 diabetes populations, 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.Results: Six eligible trials, including 10419 patients, were identified and considered eligible for the analyses. GLP-1RAs were associated with a significant reduction in MACE incidence (HR: 0.87, 95% confidence interval: 0.80–0.94; I2:0%). The analysis of the secondary endpoints 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%). Conclusions: 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 benefit in cardiovascular outcomes is independent of metformin use when GLP-1Ras are administered.