Empagliflozin in nondiabetic individuals with calcium and uric acid kidney stones: a randomized phase 2 trial.

Summary

In a randomized, double-blind, placebo-controlled crossover trial in nondiabetic stone formers (n=53), empagliflozin reduced urinary relative supersaturation (RSR) for calcium phosphate by 36% in calcium stone formers and for uric acid by 30% in uric acid stone formers. No serious or prespecified adverse events occurred over the short treatment periods.

Key Findings

• Empagliflozin reduced RSR for calcium phosphate by 36% in calcium stone formers.
• Empagliflozin reduced RSR for uric acid by 30% in uric acid stone formers.
• No serious or prespecified adverse events were observed during 2-week treatment periods.
• Effect was specific by stone type; no significant changes in non-target RSRs.

Clinical Implications

Empagliflozin could become a preventive option for calcium phosphate and uric acid stones in nondiabetic patients, pending longer trials assessing stone recurrence, safety, and metabolic effects.

Limitations

• Short treatment duration (2 weeks per period) and single-center design.
• Per-protocol primary analysis with modest sample size; clinical recurrence not assessed.

Future Directions

Conduct multicenter, longer-term RCTs powered for stone recurrence, safety, and patient-reported outcomes; explore mechanisms of reduced supersaturation in specific stone phenotypes.