Effects of glucagon‐like peptide‐1 receptor agonists on cardiovascular and renal outcomes: A <scp>meta‐analysis</scp> and <scp>meta‐regression</scp> analysis
Satoshi Yoshiji, Hiroto Minamino, Daisuke Tanaka, Shunsuke Yamane, Norio Harada, Nobuya Inagaki
Abstract
Abstract Aim 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. Materials and Methods 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. Results 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; R 2 = 0.65) and the composite renal outcome ( P = .040; R 2 = 0.85), respectively. On the contrary, weight reduction was not associated with any outcome, including MACE ( P = .390). Conclusions 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.