Urinary Stone Recurrence After Initiation of GLP-1-Based Therapy: A Romanian Retrospective Cohort Study of Clinical, Renal, and Hydration-Related Factors

Background: Glucagon-like peptide-1 receptor agonists and dual GIP/GLP-1 receptor agonists produce substantial weight loss and improve glycemic control, but their relationship with urinary stone recurrence remains incompletely characterized. We evaluated clinically and radiologically confirmed recurrent stone episodes occurring after initiation of semaglutide or tirzepatide. Methods: This retrospective single-center cohort screened 168 adults receiving semaglutide or tirzepatide. Four patients with previous bariatric surgery, 33 without at least 6 months of post-initiation clinical follow-up, and five with hyperparathyroidism were excluded, leaving 126 participants. Follow-up was calculated from GLP-1-based therapy initiation to the last documented clinical or imaging assessment. Recurrence required a stone episode documented before treatment initiation and a new symptomatic or radiologically progressive stone event after initiation. Results: The cohort included 94 semaglutide and 32 tirzepatide users. Median follow-up was 9 months [IQR 8–12]. Thirteen patients (10.3%; 95% CI 6.1–16.9%) had a recurrent episode after treatment initiation. No measured demographic, metabolic, renal, hydration-related, electrolyte, or treatment characteristic clearly differentiated patients with and without recurrence. Allopurinol use was more frequent among recurrent stone formers in an unadjusted analysis, a finding considered exploratory and likely affected by confounding by indication. Conclusions: In this single-arm cohort, 10.3% of patients had clinically and radiologically documented stone recurrence after GLP-1-based therapy initiation. The study describes post-initiation events but cannot estimate treatment-attributable risk because it lacked an untreated comparator, pre-treatment incidence-rate analysis, standardized surveillance, and complete exposure data. Larger prospective comparator studies with baseline imaging, time-to-event follow-up, complete urinary chemistry, and treatment-dose data are required.