Effects of glucagon‐like peptide‐1 receptor agonists on cardiovascular and renal outcomes: A meta‐analysis and meta‐regression analysis

To evaluate the cardiovascular and renal outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the associations between these outcomes and HbA1c or weight reduction.We searched PubMed/MEDLINE, EMBASE, and CENTRAL databases for randomized, placebo-controlled trials of GLP-1 RAs reporting major adverse cardiovascular events (MACE; a composite of cardiovascular mortality, stroke, and myocardial infarction) as the primary outcome. We conducted a meta-regression analysis of primary and secondary outcomes with HbA1c or weight reduction following a meta-analysis with a random-effects model for these outcomes.We extracted data of 60 800 individuals from eight eligible studies (ELIXA, LEADER, SUSTAIN-6, EXSCEL, HARMONY, PIONEER 6, REWIND, and AMPLITUDE-O). GLP-1 RAs reduced MACE (hazard ratio [HR] 0.86; 95% CI: 0.80-0.93; P < .001) and secondary outcomes including the composite renal outcome (0.80; 0.73-0.87; P < .001). In meta-regression analysis, every 1% reduction in HbA1c was associated with 26% and 35% decreases in the logarithm of HR of MACE (P = .044; R2 = 0.65) and the composite renal outcome (P = .040; R2 = 0.85), respectively. On the contrary, weight reduction was not associated with any outcome, including MACE (P = .390).The reduction in HbA1c, but not body weight, is associated with cardiovascular and renal outcomes. The magnitude of HbA1c reduction can be a surrogate for the cardiovascular and renal benefits of treatment with GLP-1 RAs.