ObjectiveGlucagon-like peptide-1 receptor agonists are established for weight management and cardiovascular risk reduction, with emerging evidence for kidney protection. Whether albuminuria-lowering effects extend to nondiabetic chronic kidney disease remains uncertain.MethodsWe performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided meta-analysis of randomized controlled trials comparing glucagon-like peptide-1 receptor agonists with placebo or standard care. Primary outcomes were change in body weight (kg) and percentage change in urinary albumin-to-creatinine ratio; change in estimated glomerular filtration rate was the secondary outcome. We conducted prespecified subgroup analyses (including glycemic status) and random-effects meta-regression to explore heterogeneity. Risk of bias assessment (2.0), small-study effects (funnel plot and trim-and-fill analyses), sensitivity analyses (leave-one-out and low-risk-only), and Grading of Recommendations Assessment, Development and Evaluation certainty ratings were applied.ResultsTen trials (n = 26,088) were included. Glucagon-like peptide-1 receptor agonists reduced body weight (mean difference, -5.85 kg; 95% confidence interval: -7.78 to -3.92) with a consistent direction of effect across studies despite heterogeneity. Glucagon-like peptide-1 receptor agonists lowered urinary albumin-to-creatinine ratio overall (mean difference, -27.94%; 95% confidence interval: -37.72 to -18.15). Stratified analyses showed a precise reduction in type 2 diabetes mellitus (mean difference, -25.70%; I2 = 0%) and a directionally concordant but less precise reduction in populations without type 2 diabetes mellitus (mean difference, -30.93%; I2 = 96%). A modest between-group difference in estimated glomerular filtration rate was also observed (mean difference, -0.82 mL/min/1.73 m2; I2 = 0%). Meta-regression indicated attenuation with longer treatment duration and greater benefit with higher baseline albuminuria; drug class and glycemic status were not consistent moderators of urinary albumin-to-creatinine ratio in prespecified subgroups. Findings were robust to multiple sensitivity analyses. Certainty of evidence was high for weight and moderate for urinary albumin-to-creatinine ratio.ConclusionsGlucagon-like peptide-1 receptor agonists were associated with clinically meaningful weight loss and lower urinary albumin-to-creatinine ratio across included trials. A directionally similar signal was observed in populations without type 2 diabetes mellitus, although interpretation of this subgroup remains limited by heterogeneity, imprecision, and the inability to evaluate intermediate glycemic phenotypes. Variability in urinary albumin-to-creatinine ratio estimates appears to reflect duration and baseline risk more than a lack of effect.
