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Impact of GLP-1 Receptor Agonists on Nephrolithiasis Risk: A TriNetX Cohort Analysis
Orleiquis Guerra, MD, Cedrick Chiu, BS, Jennifer Fantasia, MD.
University of Massachusetts Chan Medical School, Worcester, MA, USA.
Introduction: Glucagon-like peptide-1 (GLP-1) agonists are increasingly utilized for glycemic control and weight management. Emerging evidence suggests that GLP-1 receptor agonists may affect the risk of nephrolithiasis development. Given the rising adoption of next-generation hypoglycemic agents, this study aims to assess the influence of GLP-1 agonists on de novo nephrolithiasis risk.
Methods: A retrospective cohort analysis was conducted using the TriNetX database. Patients 18 years-old and older prescribed GLP-1 receptor agonists were stratified into three cohorts based on BMI: normal-weight (18.5-24.9 kg/mē), overweight (25-29.9 kg/mē), and obese (30-49.9 kg/mē). Propensity score matching was performed to adjust for potential confounders. The odds ratio (OR) was calculated to assess nephrolithiasis risk at 1 and 5 years.
Results: A total of 1,562,811 patients were included. In the normal-weight cohort 73,917(4.73%), no GLP-1 use was associated with a progressively increasing risk of nephrolithiasis in females, with statistically significant ORs at 1 year (OR 1.26, p=0.0070) and 5 years (OR 1.461, p<0.0001). Males in this cohort exhibited a significant increase only at 5 years (OR 1.218, p=0.0077). In the overweight cohort, females not using GLP-1s demonstrated no significant risk difference at 1 year but had a mild increase at 5 years (OR 1.199, p<0.0001). Males in this cohort showed no significant difference at 1 year but exhibited a significant increase at 5 years (OR 1.248, p<0.0001). In the obese cohort, no GLP-1 patients had a consistently increased risk of nephrolithiasis across all time points for both sexes, with the highest ORs observed at 5 years (Females: OR 1.394, p<0.0001; Males: OR 1.334, p<0.0001).
Conclusion: Our study suggests GLP-1 agonists may have lithoprotective effects though the precise mechanism remains unclear. These findings emphasize the need for further research to understand the underlying mechanisms and assess their long-term impact on kidney stone prevention.
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