The Effect of Sodium-Glucose Cotransporter 2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists on 24-Hour Urine Parameters

Key Points In a cross-sectional study, sodium-glucose cotransporter 2 inhibitors were associated with a significant increase in urine volume and urine citrate. Glucagon-like peptide-1 receptor agonists were not associated with any significant changes in 24-hour urine parameters that affect stone formation. Background Emerging data suggest sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) may lower stone risk. Methods We characterized 24-hour urine parameters among patients with kidney stone disease receiving these agents using Medicare claims from beneficiaries with urine collections processed by a central laboratory between January 2010 and December 2019. We identified a cross-sectional cohort with diabetes and a prescription fill for SGLT2is or GLP-1RAs within the 6 months preceding their urine collection and matched controls. We additionally identified a subset of patients who performed two collections and had a prescription fill for SGLT2is or GLP-1RAs before the second collection, but not the first. We compared across 24-hour urinary parameters in both cohorts and adjusted for multiple comparisons. Results The cross-sectional cohort included 124 patients with a prescription fill for SGLT2is (and 620 matched controls) and 349 patients with a prescription fill for GLP-1RAs (and 349 matched controls). Compared with controls, patients on SGLT2is had a higher mean urine citrate (838 versus 636 mg; P < 0.01) and volume (2.4 versus 2.0 L; P < 0.01) with improved calcium phosphate supersaturation ( P < 0.01). Lower urine pH and higher sulfate and uric acid were observed in the SGLT2i group ( P < 0.01 for each). There were no significant differences in urine parameters with GLP-1RA. In the longitudinal analyses of SGLT2is (59 patients) and GLP-1RAs (154 patients), there were no significant differences in urinary parameters. Conclusions SGLT2is were associated with higher urine volume and citrate in a cross-sectional cohort. GLP-1RAs were not associated with changes that would reduce stone risk.