SGLT2 Inhibitors in Nephrolithiasis: Emerging Evidence and What Urologists Need to Know.

Abstract

Background: Nephrolithiasis frequently coexists with type 2 diabetes, obesity, gout, chronic kidney disease, and other cardiometabolic disorders. Sodium-glucose cotransporter 2 (SGLT2) inhibitors may influence stone formation through effects on glucosuria, natriuresis, urine volume, urinary citrate, pH, urate handling, and relative supersaturation. This review aimed to examine the current mechanistic, biochemical, and clinical evidence linking SGLT2 inhibition to nephrolithiasis, with particular attention to its relevance for urological practice.

Methods: A clinically oriented narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. The final search was performed on 1 July 2026. A total of 15 studies were included. Randomised trials, pooled and post hoc analyses, observational and comparative-effectiveness studies, meta-analyses, human mechanistic studies, and relevant experimental investigations were considered. Evidence was synthesised narratively according to biological mechanisms, urinary chemistry and relative supersaturation, randomised evidence, and observational clinical outcomes. Clinical stone events were analysed separately from surrogate urinary endpoints.

Results: SGLT2 inhibition is associated with reproducible increases in urinary citrate and variable effects on urine volume, urinary pH, and the excretion of calcium, phosphate, and urate. Short-term mechanistic studies suggest reductions in calcium phosphate supersaturation and, in selected uric acid stone formers, uric acid supersaturation, whereas effects on calcium oxalate supersaturation remain inconsistent. Observational studies and secondary analyses of randomised trials generally indicate fewer nephrolithiasis events among SGLT2 inhibitor users; however, most outcomes were based on adverse-event reporting or administrative codes and lacked stone composition, standardised imaging, urinary phenotyping, and recurrence adjudication.

Conclusions: SGLT2 inhibitors may favourably modify selected lithogenic pathways, but their effects appear phenotype-dependent and have not yet been shown to directly prevent stone recurrence. They should not be initiated solely for the prevention of nephrolithiasis. In patients with established cardiovascular, renal, or metabolic indications, their potential urinary effects may represent an additional benefit. Dedicated long-term randomised studies with stone-specific endpoints are required.