GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs

Abstract

Background A meta-analysis is presented of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RA) versus placebo on cardiorenal outcomes in patients with type 2 diabetes mellitus (T2DM). Methods We did an electronic search up to June 30, 2021, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) and 95% CI (confidence intervals). We included data from 8 CVOTs and 60,080 patients (72.4% with established cardiovascular disease). Results GLP-1RA reduced major cardiovascular events (MACE) by 14% (HR\u2009=\u20090.86, 95% CI 0.79–0.94, P\u2009=\u20090.006) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (P\u2009=\u20090.127). GLP-1RA also reduced the risk\xa0of cardiovascular death by 13% (P\u2009=\u20090.016), nonfatal stroke by 16% (P\u2009=\u20090.007), hospitalization for heart failure by 10% (P\u2009=\u20090.023), all-cause mortality by 12% (P\u2009=\u20090.012), and the broad composite kidney outcome by 17% (P\u2009=\u20090.012), which was driven by a reduction in macroalbuminuria only (HR\u2009=\u20090.74, 0.67–0.82, P\u2009<\u20090.001). Conclusions GLP-1RA have moderate benefits on MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also have robust benefits on reducing the incidence of macroalbuminuria.