The potential role of Sodium/Glucose Cotransporter 2 inhibitors in the treatment of cystinuria.

The Maillard reaction is a non-enzymatic reaction between an amino acid and carbohydrate. We hypothesized that continuous washing of cystine stones with glucose could theoretically prevent growth of an existing cystine stone or even reduce its size leading to a decrease in stone events. Sodium/Glucose Cotransporter 2 (SGLT2) inhibitors, well known for inducing glucosuria, were used to test this hypothesis in an initial series of patients. Patients with cystinuria from September 2019 to May 2023 who received off-label dapaglifozin (Farxiga™) were identified. Patients were allowed to continue thiol and alkalinizing agents per standard of care. A symptomatic stone event was defined by stone passage or surgical intervention. Ten cystinuric patients were prescribed SGLT2 inhibitors with a median follow up of 13.5 months. Each patients' historic stone event rate was compared to the event rate while prescribed SGLT2 medication. Overall, 70% of patients experienced fewer stone events and half had stable stone volume during therapy. Eight patients had negative cystine capacity at baseline, yet seven experienced fewer stone events while on medication: four experienced no stone growth. One patient was taken off the SGLT2 inhibitor due to an adverse reaction; three others experienced mild, self-resolving effects and yet stayed on the medication. Cystinuric patients treated with a SGLT2 inhibitor experienced fewer stone events while on medication compared to their historic rates and exhibited decreased or stable stone growth. There were few medication related side effects. SGLT2 inhibitors may be a promising long-term therapy for patients with cystinuria.