Graduate Student Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, United States
Background: Sodium glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i) are both second-line glucose-lowering treatments in patients with type 2 diabetes (T2D). Limited real-world evidence is available regarding the direct comparison of these two therapeutic classes' cardiovascular (CV) and safety outcomes.
Objectives: We sought to evaluate the comparative risk of CV and safety outcomes for SGLT2i versus DPP4i in patients with T2D.
Methods: Using 2012-2019 Medicare Part D data, we selected T2D patients who initiated either SGLT2i or DPP4i from 04/01/2013 to 12/31/2018. The primary effectiveness outcome was time to major adverse CV events (MACE), defined as the composite of myocardial infarction (MI), stroke, and all-cause death. Secondary effectiveness outcomes included time to stroke, MI, death, and hospitalization for heart failure (HHF). Safety outcomes included time to hypoglycemia, non-vertebral fracture, hospitalization for genitourinary tract infections, acute kidney injury (AKI), diabetic ketoacidosis (DKA), and lower-extremity amputation (LEA). Cox proportional hazard models were conducted to compare the risk of each outcome for SGLT2i versus DPP4i between propensity score-matched treatment groups.
Results: After 1:2 propensity score matching, the final cohort included a total of 9,706 SGLT2i initiators and 18,418 DPP4i initiators, respectively. The mean age (SD) was 68 (11) years, and 52.5% were female. Compared to DPP4i, SGLT2i was associated with a significantly lower risk of MACE [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.63-0.95], HHF (0.61, 95% CI 0.49-0.75), stroke (0.73, 95% CI 0.54-0.98) and death (0.46, 95% CI 0.36-0.59), but not in MI (0.85, 95% CI 0.64-1.13). There were no significant differences in the risk of non-vertebral fractures (1.07, 95% CI 0.89-1.30), DKA (0.90, 95% CI 0.47-1.74), and LEA (1.38, 95% CI 0.82-2.32) between treatment groups. The risks of hypoglycemia (0.28, 95% CI 0.11-0.73), hospitalization for genitourinary tract infections (0.55, 95% CI 0.38-0.81), and AKI (0.19, 95% CI 0.08-0.41) were lower for SGLT2i compared to DPP4i.
Conclusions: SGLT2i demonstrated superior effectiveness in the prevention of cardiovascular events and a lower risk of hypoglycemia, hospitalization for genitourinary tract infections, and AKI compared to DPP4i.
