Kidney and Cardiovascular Outcomes Among Patients With CKD Receiving GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of Randomized Trials.

Rationale & objective: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve cardiac and kidney outcomes in patients with diabetes; however their efficacy in individuals with reduced estimated glomerular filtration rate (eGFR) is uncertain. This study evaluated the effects of GLP-1RAs on kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD).

Study design: Systematic review and meta-analysis of randomized controlled trials (RCTs) reported through May 25, 2024.

Setting & study populations: Adult participants in RCTs with baseline eGFR <60 mL/min/1.73 m².

Selection criteria for studies: RCTs including adults (≥18 years old) with varying degrees of kidney function, including individuals with CKD characterized by a baseline eGFR of less than 60 mL/min/1.73 m², that compared GLP-1RAs with control treatments with respect to a composite kidney outcome, all-cause mortality, or a composite CV disease outcome. From among 212 screened studies, 12 trials involving that included participants with baseline eGFR <60 mL/min/1.73 m² were included.

Data extraction: Two independent investigators extracted the data.

Analytical approach: Pooled odds ratios (ORs) for composite kidney outcome, all-cause mortality, and composite CV outcome were estimated using random-effects models. Evidence certainty was assessed using the GRADE system.

Results: 17,996 RCT participants with baseline eGFR <60 mL/min/1.73 m² were included in analyses. GLP-1RAs were significantly associated with a reduced risk of the composite kidney outcome (OR: 0.85 [95% CI 0.77-0.94]; p=0.001) with low heterogeneity (I²<0.01%). GLP-1RAs were also associated with a reduced the risk of a >30% eGFR decline (OR: 0.78, p=0.004), a >40% decline (OR: 0.76, p=0.01), and a >50% decline (OR: 0.72, p<0.001). Risk of all-cause mortality was also lower in the GLP-1RA group (OR: 0.77 [95% CI 0.60-0.98]; p=0.03), though there was high heterogeneity (I²=71.6%). Composite CV outcomes were also lower with the use of GLP-1R (OR: 0.86 [95% CI 0.74-0.99]; p=0.03; I²=40.3%). Sensitivity analyses restricted to human GLP-1 backbone agents showed enhanced benefits.

Limitations: Inconsistent kidney outcome definitions, focus on diabetic populations in most studies, and potential publication bias.

Conclusions: GLP-1RAs improved kidney and cardiovascular outcomes, and survival in patients with CKD enrolled in an array of clinical trials.