Safety of Sodium–Glucose Cotransporter 2 Inhibitors in Older Adults With Type 2 Diabetes: A Cohort Study

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have demonstrated cardiorenal benefits in individuals with type 2 diabetes, but safety data in older adults remain limited. We evaluated the real-world safety of SGLT2is compared with dipeptidyl peptidase 4 inhibitors (DPP-4is) among individuals aged ≥75 years with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a population-based, active-comparator, new-user cohort study using administrative health databases from British Columbia, Canada. We included individuals aged ≥75 years with type 2 diabetes initiating SGLT2is or DPP-4is between 1 January 2021 and 31 December 2023. Primary outcomes were infection, diabetic ketoacidosis, acute kidney injury, fall, fracture, and all-cause hospitalization. Cox regression with propensity score-based standardized mortality ratio weighting was used to estimate hazard ratios (HRs). RESULTS: The study included 4,997 SGLT2i initiators (median age, 79 years; 37% women) and 1,289 DPP-4i initiators (median age, 82 years; 50% women). Compared with DPP-4i initiation, SGLT2i initiation was associated with lower risks of acute kidney injury (HR 0.76, 95% CI 0.60-0.95) and all-cause hospitalization (HR 0.87, 95% CI 0.77-0.98), with no difference in risk of infection. No differences were observed in risk of diabetic ketoacidosis, falls, or fractures, although CIs were compatible with both benefit and harm. CONCLUSIONS: In individuals aged ≥75 years with type 2 diabetes, SGLT2i initiation was not associated with increased risk of harm compared with DPP-4i initiation, although estimates were imprecise for some outcomes. These findings may support consideration of SGLT2is as a treatment option in this population.