Frailty and low body mass index as key determinants of sodium-glucose cotransporter 2 inhibitor-specific adverse event-related discontinuation in adults aged ≥75 years: A multicenter real-world retrospective cohort study.

AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are increasingly prescribed to older adults; however, data regarding their tolerability and drug-specific adverse events (AEs) in very elderly Asian populations, particularly among individuals with frailty or low body mass index (BMI), remain limited. We aimed to determine the incidence of SGLT2i-specific AE-related treatment discontinuation and to identify associated risk factors among Japanese adults aged ≥75 years. MATERIALS AND METHODS: We conducted a multicenter retrospective cohort study including Japanese adults aged ≥75 years who newly initiated SGLT2is between 2014 and 2024. Medical records were reviewed for 180 days. SGLT2i-specific AEs were defined as genitourinary infection, volume depletion, acute kidney function decline, and diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome. Cox proportional hazards models were used for identifying predictors. RESULTS: A total of 616 patients were included (mean age, 81.3 years; mean BMI, 24.0 kg/m2). The 180-day cumulative incidence of SGLT2i-specific AE-related discontinuation was 9.1%. Multivariable analysis identified Clinical Frailty Scale ≥5 (hazard ratio [HR], 4.67; P < 0.001) and BMI <22 kg/m2 (HR, 2.53; P = 0.003) as independent predictors of discontinuation. CONCLUSIONS: SGLT2 inhibitors were generally well tolerated among adults aged ≥75 years. Frailty and low BMI were the principal determinants of AE-related treatment discontinuation, whereas chronological age was not independently associated with the risk. Assessment of physiological reserve may help identify patients requiring closer monitoring and support the safe use of SGLT2 inhibitors in older adults.