915-P: Head-to-Head Comparison of Dapagliflozin vs. Empagliflozin—Cardiovascular and Safety Events

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) are recommended for adults with type 2 diabetes (T2D) at high cardiovascular (CV) risk. However, the comparative effectiveness and safety of dapagliflozin and empagliflozin is unknown. We compared these two drugs for CV and safety events. Methods: In three US claims databases (commercial and Medicare), we identified adults with T2D who initiated dapagliflozin or empagliflozin during 08/2014-06/2020. Endpoints evaluated were 2-point MACE (a composite of myocardial infarction (MI) or stroke), hospitalization for heart failure (HHF), MI, stroke, all-cause death, and safety outcomes (diabetic ketoacidosis, amputations, fractures, urinary tract infections, genital infections, acute kidney injury, and hypoglycemia). Database-specific models were weighted using propensity score matching-weights to adjust for confounding, and hazard ratios (HRs) were pooled across databases. Results: We identified 107,602 dapagliflozin and 272,014 empagliflozin initiators. Compared with empagliflozin, dapagliflozin initiators were younger (mean age 56 vs 61 years) and had less CV disease at baseline (19% vs 31%). After adjusting for 129 confounders, compared with empagliflozin at both 10 mg and 25 mg doses, dapagliflozin showed similar risk for most CV outcomes, including MI/stroke (HR=0.96, 95% CI=0.88-1.03). However, dapagliflozin initiators had a higher risk of HHF (HR=1.17, 1.02-1.33), driven by the lower dose of dapagliflozin (HR5mg=1.23, 1.04-1.46 for dapagliflozin 5mg; HR10mg=1.08, 0.88-1.32 for dapagliflozin 10mg). Compared to those on empagliflozin, dapagliflozin initiators had a lower risk of genital infections (HR=0.93, 0.90-0.96) across all doses and a similar risk of the other safety outcomes. Conclusion: Dapagliflozin has similar CV benefits at doses proven effective in cardiovascular outcome trials, i.e., dapagliflozin 10mg, but the 5 mg dose may not have similar CV effectiveness. Disclosure H. Shin: None. J.M. Paik: None. B.M. Everett: Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Ipsen Pharmaceuticals, Provention Bio, Inc. R. Glynn: Research Support; Amarin Corporation, Kowa Pharmaceuticals America, Inc., Novartis AG, Pfizer Inc. D.J. Wexler: Other Relationship; Novo Nordisk. E. Patorno: Research Support; Boehringer-Ingelheim, Food and Drug Administration (FDA), National Institutes of Health, Patient-Centered Outcomes Research Institute. Funding Patient Centered Outcomes Research Institute (DB-2020C2-20326)