Effect of glucagon-like peptide 1 receptor agonists on the renal protection in patients with type 2 diabetes: A systematic review and meta-analysis

Glucagon-like peptide 1(GLP-1) receptor agonists are used in patients with type 2 diabetes as hypoglycemic drugs; a growing body of evidence has clarified their renoprotective benefits. We performed a meta-analysis to summarize the most recent evidence on the renal benefits of GLP-1 receptor agonists from clinical trials of patients with type 2 diabetes. This meta-analysis used a fixed-effects model to estimate the risk ratio (RR) with 95% confidence intervals (CIs) to investigate the effect of GLP-1 receptor agonists on the renal protection. The outcomes were a composite renal outcome, estimated glomerular filtration rate (eGFR) decrease, new macroalbuminuria, doubling of serum creatinine, end-stage renal disease (ESRD) and renal death. We also checked the composite renal outcome of the patient subgroups based on the structural source of human GLP-1 or exendin-4. Among the 12 articles screened, seven studies involving 48101 patients met pre-specified criteria and were included. In general, the use of GLP-1 receptor agonists reduced the risk of the composite renal outcome by 17% (RR 0·83 [95% CI 0·79–0·88]; P < 0·00001), with no significant interaction in subgroups analysis (P = 0.66); the risk of new-onset of persistent macroalbuminuria was reduced by 25% (RR 0·75 [95%CI 0·69–0·81]; P < 0·00001) compared to placebo. However, GLP-1 receptor agonists had no significant effect on eGFR decrease (RR 0·92 [95% CI 0·83–1.01]; P = 0·09), doubling of serum creatinine (RR 0·97 [95% CI 0·78–1.21]; P = 0·79), or end-stage renal disease (RR 0·81 [95% CI 0·62–1.06]; P = 0·12) compared to placebo or insulin glargine (AWARD-7) in patients with type 2 diabetes. GLP-1 receptor agonists, regardless of their structural homology, have significant benefits in reducing the risk of the composite renal outcome, especially in new macroalbuminuria compared with placebo or insulin glargine in patients with type 2 diabetes.