探討類升糖素胜肽-1 與尿路結石的相關性：以TriNetX資料庫回溯性分析

劉佳旻¹、李珮欣¹、劉展榮^1,2

成功大學醫學院附設醫院 泌尿部¹;成功大學醫學院 泌尿部²

Exploring the Risk of Nephrolithiasis Associated with Glucagon-like Peptide-1 Agonists: A Retrospective TriNetX Data Analysis

Chia-Min Liu¹, Pei-Hsin Li¹, Chan-Jung Liu^1,2

Department of Urology, National Cheng Kung University Hospital, Tainan, Taiwan¹;

 Department of Urology, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan²

Purpose: Nephrolithiasis is linked to diabetes mellitus (DM) and obesity. Given the limited effectiveness of medications in preventing nephrolithiasis, anti-DM drugs like glucagon-like peptide-1 agonists (GLP-1A), commonly used for type 2 DM and obesity, are considered potential treatments. However, recent data indicate that GLP-1A does not have anti-lithogenic effects based on 24-hour urine chemistry. Due to the high recurrence rate of nephrolithiasis and its economic burden, understanding GLP-1A’s influence on nephrolithiasis is crucial for exploring potential therapeutic benefits.

Materials and Methods: This is a retrospective cohort study utilizing the TriNetX database to evaluate the risk of nephrolithiasis and GLP-1A, which includes liraglutide (LIRA), semaglutide (SEMA), and dulaglutide (DULA), between January 1, 2016, and December 31, 2023. Dipeptidyl peptidase 4 inhibitors (DPP4i), a second-line DM medication, served as the active comparator. Propensity score matching (PSM) was performed by age, BMI, and confounding comorbidities. Kaplan–Meier and risk analyses were performed, and hazard ratio (HR) was calculated.

Results: After matching, the LIRA and DPP4i cohorts each contained 142,896 patients (Figure). The LIRA group had a significantly higher risk of nephrolithiasis compared to the DPP4i group (HR = 1.037, 95% CI: 1.006-1.069, p = 0.021). When comparing SEMA with DPP4i, each cohort contained 312,538 patients after matching. The SEMA group had a significantly higher risk of nephrolithiasis than DPP4i group ([HR] = 1.191, 95% CI: 1.161-1.223, p < 0.001). Finally, after matching, each cohort in the comparison of DULA and DPP4i comprised 261,124 patients. The DULA group also had a significantly higher risk of nephrolithiasis than DPP4i group ([HR] = 1.099, 95% CI: 1.072-1.128, p < 0.001).

Conclusions: GLP-1A is associated with the risk of nephrolithiasis, and of the three GLP-1A, SEMA has the highest correlation with nephrolithiasis risk.