GLP‐1 receptor agonists for prevention of cardiorenal outcomes in type 2 diabetes: An updated meta‐analysis including the REWIND and PIONEER 6 trials

Abstract

A meta‐analysis of cardiovascular outcome trials (CVOTs) comparing glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and placebo concerning cardiorenal outcomes in patients with type 2 diabetes (T2D) is presented. An electronic search without language restrictions up to June 15, 2019 was conducted to determine eligible trials. A meta‐analysis of available trial data was undertaken, using a random‐effects model to calculate overall hazard ratios (HRs) and 95% confidence intervals (CIs). Data from seven CVOTs, comprising 56\u2009004 patients (68.9% with established cardiovascular disease) were included. GLP‐1RA reduced major cardiovascular events (MACE) by 13% (HR, 0.87; 95% CI, 0.80–0.96; P =\u20090.011) with a non‐significant heterogeneity between subgroups of patients with and without cardiovascular disease (CVD) (P =\u20090.220). GLP‐1RA also reduced the risk of cardiovascular death by 12%, of non‐fatal stroke by 16%, of hospitalization for heart failure by 9%, of all‐cause mortality by 11%, and the broad composite kidney outcome by 17%; the latter appeared to be driven only by a reduction in macroalbuminuria (HR, 0.76 [0.68–0.86]; P =\u20090.003). GLP‐1RAs have moderate benefits concerning MACE, and also reduce hospitalization for heart failure and all‐cause mortality; they also robustly reduce the incidence of macroalbuminuria, without affecting the progression of diabetic renal disease.