Safety of Sodium–Glucose Cotransporter 2 Inhibitors in Older Adults With Type 2 Diabetes: A Cohort Study
Hanin Harbi, Michael Nesrallah, Greg Carney, Colin Dormuth, Jacob V. Stidsen, Iliana C. Lega, Lisa M. McCarthy, Guillaume Grenet, Anshula Ambasta, Raha Eskandari, Anton Pottegård, Wade ThompsonOBJECTIVE
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.