Higher genetic expression of the glucagon-like peptide 1 receptor gene, linked to glucagon-like peptide 1 receptor agonists, is associated with reduced kidney disease progression risk, even after adjusting for diabetes and obesity, according to a recent study.
The genetic association study from the Veterans Affairs Million Veteran Program evaluated the nephroprotective potential of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in a cohort of 353,153 U.S. veterans, analyzing GLP1R gene expression as a genetic proxy. The study aimed to determine whether elevated GLP1R expression could reduce the risk of kidney disease progression, independently of factors such as obesity and diabetes.
Published in JAMA Network Open, the study found a modest association between higher GLP1R gene expression and decreased risk of kidney disease progression. Specifically, increased GLP1R expression was associated with a 4% lower risk of end-stage kidney disease (ESKD) or a 40% decline in estimated glomerular filtration rate (eGFR), as demonstrated in both unadjusted (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.92-0.99; P = .02) and fully adjusted models (HR, 0.96; 95% CI, 0.92-1.00; P = .04), adjusting for age, sex, body mass index, and diabetes status.
During a median follow-up of 5.1 years, kidney disease progression—defined as reaching ESKD or a 40% eGFR reduction—was observed in 16,327 participants (4.6%). Findings were consistent across subgroups, including patients with and without diabetes, as well as across varying body weights, supporting the potential nephroprotective associations of GLP1R gene expression across a broader patient population.
These results align with prior clinical trials, such as the FLOW study, which identified renal benefits of GLP-1RAs in patients with diabetes. The present findings indicate an association between GLP-1RAs and kidney protection that may extend beyond glucose and weight management effects. Further clinical trials are warranted to evaluate GLP-1RA efficacy in reducing kidney disease progression across diverse patient populations.
Full disclosures can be found in the published study.
