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The effect of GLP-1 receptor agonists on renal outcomes: a systematic review and meta-analysis
Takaya Sasaki1,2, Samantha M Giang3,4, Jiajia Wu5
1Renal and Metabolic Division, George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Background And Hypothesis:
Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are anti-hyperglycaemic agents, with cardioprotective effects, however their renal protective effects remain unclear. We aimed to assess the effects of GLP1-RAs on renal outcomes in patients with or without diabetes.
Methods:
We performed a systematic review and meta-analysis with Medline, EMBASE and the Cochrane Register searched to December 2024. The primary outcome was the composite of kidney failure (defined as estimated glomerular filtration rate <15 mL/min/1.73 m2) or dialysis requirement, worsening of renal function and changes in proteinuria. Subgroup analysis was performed based on diabetic status, a (CKD) and individual GLP1-RA drugs. Relative risks (RR) with 95% confidence intervals (CI) for individual trials were pooled using random effects models.
Results:
We identified 19 trials including 90 882 patients. Mean age was 60.8 years and mean follow-up was 25.9 months. GLP1-RAs were associated with a 19% reduction in the risk of primary renal outcome (RR 0.81, 95% CI 0.73-0.89), a 12% reduction in renal functional decline (RR 0.88, 95% CI 0.81-0.95) and a 0.45 mL/min/1.73 m2 reduction in yearly loss [16 trials, mean difference (MD) 0.45, 95% CI 0.10-0.81]. GLP1-RAs also reduced microalbuminuria by 24% (RR 0.76, 95% CI 0.71-0.82), HbA1c (units: %) by 0.61 (MD -0.61, 95% CI -0.76 to -0.49) and body weight by 5 kg (MD -5.24, 95% CI -7.46 to -3.02). Although there were no significant differences in progression to kidney failure (RR 0.86, 95% CI 0.71-1.05), GLP1-RAs reduced the incidence of major adverse cardiovascular events by 15% (RR 0.85, 95% CI 0.81-0.90) and all-cause mortality by 14% (RR 0.86, 95% CI 0.82-0.91). No significant differences were seen in severe adverse events (RR 0.96, 95% CI 0.90-1.01). However, there were more gastroenterological side effects.
Conclusions:
GLP1-RAs demonstrated cardiovascular and renal benefits. Further high-quality randomized trials assessing their effects in patients without diabetes, with or without proteinuria and/or CKD are needed.
Insights
Glucagon-like peptide-1 receptor agonists (GLP1-RAs) show significant renal protective effects, reducing primary renal outcomes by 19%. These agents also offer cardiovascular benefits, but further research is needed for non-diabetic patients.
Area of Science:
- Nephrology
- Cardiology
- Endocrinology
Background:
- Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are established anti-hyperglycaemic agents with known cardioprotective properties.
- The renal protective effects of GLP1-RAs remain less understood, necessitating further investigation.
Purpose of the Study:
- To systematically evaluate the impact of GLP1-RAs on renal outcomes in patients, both with and without diabetes.
- To synthesize evidence from existing trials to clarify the renal benefits of GLP1-RAs.
Main Methods:
- A comprehensive systematic review and meta-analysis of randomized controlled trials was conducted, searching databases up to December 2024.
- The primary renal outcome included kidney failure, worsening renal function, and changes in proteinuria.
- Pooled relative risks and confidence intervals were calculated using random-effects models, with subgroup analyses based on diabetic status and CKD.
Main Results:
- GLP1-RAs were associated with a 19% reduction in the primary renal outcome and a 12% reduction in renal functional decline.
- A significant decrease in yearly loss of estimated glomerular filtration rate (eGFR) and microalbuminuria was observed.
- While not significantly impacting progression to kidney failure, GLP1-RAs demonstrated reductions in major adverse cardiovascular events (MACE) and all-cause mortality.
Conclusions:
- GLP1-RAs exhibit significant renal and cardiovascular protective benefits.
- Further high-quality randomized trials are warranted to assess GLP1-RA effects in diverse patient populations, including those without diabetes and with varying degrees of proteinuria and chronic kidney disease (CKD).
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