Glucosuria as a Marker of Adherence to Sodium-Glucose Cotransporter 2 Inhibitors and Clinical Outcomes in Real-World Practice

BACKGROUND: Medication non-adherence contributes to the efficacy-effectiveness gap in real-world practice. Glucosuria, routinely measured on urinalysis, may serve as an objective proxy for assessing medication adherence to sodium-glucose cotransporter 2 (SGLT2) inhibitors, a class of medications that reduce the risks of kidney disease, heart failure, and mortality. METHODS: We leveraged two cohorts from the Optum Labs Data Warehouse real-world data (2014-2023): Cohort 1 included 3,987 patients with SGLT2 inhibitor pharmacy claims and a urinalysis performed both before and during active fill periods; cohort 2 included 45,711 patients prescribed SGLT2 inhibitors with urinalysis performed within 6 months after initiation. Glucosuria was defined as urine glucose 2+ or greater. Cohort 2 was followed for a mean of 3.3 years for all-cause mortality, heart failure hospitalization, end-stage kidney disease; fractures were used as a negative control outcome. RESULTS: In cohort 1, SGLT2 inhibitor use (vs. no use) was associated with 18.1-fold higher odds of glucosuria (95% CI, 16.4-20.0), adjusted for diabetes status. In cohort 2, 26,657 (58%) had glucosuria within 6 months of SGLT2 inhibitor initiation, suggesting adherence. After inverse probability of treatment weighting, glucosuria was associated with lower risks of all-cause mortality (HR, 0.78; 95% CI, 0.73-0.83), heart failure hospitalization (HR, 0.87; 95% CI, 0.78-0.98), and end-stage kidney disease (HR, 0.73; 95% CI, 0.58-0.91) compared to no glucosuria. No association was observed with fractures (HR, 1.00; 95% CI, 0.95-1.06). CONCLUSIONS: Glucosuria was associated with SGLT2 inhibitor adherence and, among patients prescribed SGLT2 inhibitors, is associated with reductions in risks of all-cause mortality, heart failure, and end-stage kidney disease.