19 Trial Meta-Analysis Finds GLP-1 RAs Have Substantial Kidney Benefits

A year after the landmark FLOW trial headlined the 61st European Renal Association (ERA) Congress, a large-scale meta-analysis at ERA 2025 is shedding further light on the potential of GLP-1 receptor agonists (GLP-1 RAs) to prevent adverse kidney outcomes.

A meta-analysis of 19 randomized controlled trials with more than 90,000 total patients, results of the study indicate use of GLP-1 RAs was associated with a reduction in the occurrence of composite renal outcomes and incidence of declining renal function, as well asa benefit on proteinuria reduction.

“Chronic kidney disease remains a progressive and incurable condition, contributing significantly to morbidity and mortality rates globally. Glucagon-like peptide-1 receptor agonists are antihyperglycemic agents, with demonstrated cardioprotective effects. However, the renal protective effects of GLP-1 RAs remain unclear,” explained investigators.

Led by a team representing institutions from Japan, Australia, and China, the meta-analysis leveraged data from the Medline, EMBASE, and the Cochrane Register databases up to December 2024 for all randomized controlled trials assessing the effects of GLP-1 RAs on renal outcomes.

The primary outcome of interest for the study was a composite renal outcome defined as development of end-stage kidney disease (ESKD) or dialysis requirement, worsening of renal function, and changes in proteinuria. Of note, investigators also planned to assess the risk of the composite outcome according to diabetic status.

Their initial search yielded more than 650 results. Upon exclusion of duplicates, an abstract review, and full text screening, 19 studies were identified for inclusion. These trials included 90,882 patients with a mean age of 60.77 years, 57% were male, and the mean follow-up was 25.9 months.

Of the 19 trials included in the study, 12 trials primarily assessed those with diabetes, 4 assessed those with obesity, 2 assessed patients with diabetes and obesity, and 1 assessed the patients with high cardiovascular risk factors.

Upon analysis, GLP-1 RAs were associated with a 19% reduction in composite renal outcomes across 10 trials (Relative Risk [RR], 0.81; 95% CI, 0.73 to 0.89). Decline in renal function dropped by 12% (RR, 0.88; 95% CI, 0.81 to 0.95), with an improvement in eGFR slope of +0.45 mL/min/1.73m² per year across 16 trials.

Key Secondary Findings:

• Microalbuminuria: Reduced by 24% (RR, 0.76; 95% CI, 0.71–0.82; n = 10 trials)
• HbA1c: Decreased by 0.61% on average (Mean difference [MD], –0.61%; 95% CI, –0.76 to –0.49; n = 15 trials)
• Body weight: Mean weight loss of 5.24 kg (MD, –5.24 kg; 95% CI, –7.46 to –3.02; n = 15 trials)
• Major adverse cardiovascular events: Reduced by 15% (RR, 0.85; 95% CI, 0.81 to 0.90; n = 15 trials)
• All-cause mortality: Decreased by 14% (RR, 0.86; 95% CI, 0.82–0.91; n = 17 trials)
• Serious adverse events: No significant differences (RR, 0.96; 95% CI, 0.90 to 1.01; n = 18 trials)

Investigators highlighted the need for further research to confirm these findings, but also pointed out 17 of the 19 trials included in the meta-analysis were considered to be at low risk of bias.1

“GLP-1 RAs demonstrated cardiovascular and renal benefits in diabetic patients. Further high-quality randomized trials assessing their effects in nondiabetic patients with or without proteinuria are needed,” investigators concluded.1

References:

1. Sasaki T, Giang S, Wu J, Gallagher M, Bellomo R, Wang A. The effect of GLP-1 receptor agonists on renal outcomes: A systematic review and metaanalysis. Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.

2. Campbell P. FLOW Trial Fortifies Semaglutide’s Role in Chronic Kidney Disease and Type 2 Diabetes. HCP Live. Published May 24, 2024. Accessed June 9, 2025. https://www.hcplive.com/view/flow-trial-fortifies-semaglutide-s-role-in-chronic-kidney-disease-and-type-2-diabetes