2201-P: Effectiveness and Safety of SGLT2i, GLP-1RA, and DPP-4i in Adults with T2D at Low-to-Moderate Cardiovascular Risk: An International Cohort Study

Introduction and Objective: The comparative effectiveness and safety of SGLT2i and GLP-1RA in adults with T2D at low-to-moderate CV risk, who constitute most of this population, remain inadequately characterized. We conducted head-to-head comparisons versus DPP4i to inform treatment selection in routine clinical practice. Methods: Using four databases from 2013-2021 (UK Clinical Practice Research Datalink; US Medicare and two commercial claims databases), we conducted three active-comparator cohort comparisons of SGLT2i, GLP-1RA, and DPP4i. Primary outcomes were modified MACE (all-cause mortality, stroke, MI), MACE (CV mortality, stroke, MI), and hospitalization for heart failure (HHF), with additional effectiveness and safety outcomes evaluated (Table). Propensity score fine-stratification weighting was used to adjust for confounding. HRs with 95% CIs were estimated. Results: Over a mean follow-up of ~12 months, both GLP-1RA and SGLT2i were associated with a lower risk of modified MACE, HHF, all-cause mortality, CV mortality, and stroke compared with DPP4i. Compared with GLP-1RA, SGLT2i showed a lower risk of HHF, but higher risks of DKA and genital infections than both GLP-1RA and DPP4i, and a higher risk of lower-limb amputations (Table). Conclusion: Among adults with T2D at low-to-moderate CV risk, GLP-1RA and SGLT2i were more effective than DPP4i in preventing adverse CV outcomes. We confirmed safety signals for SGLT2i. Disclosure H. Cho: None. W. Alkabbani: None. J. Ortega-Montiel: None. H. Yin: None. S. Cromer: Other - Spouse is employee of Depuy Synthes; Current; Johnson Current; Novo Nordisk. Consultant; Ended; Kowa Company, Ltd., Merck Ended; Novo Nordisk. Other - Royalties; Current; UpToDate. Other - Associate Editor; Current; Circulation. J. Paik: None. D. Wexler: Other - Data Monitoring Committee; Ended; Novo Nordisk. Other - Data Monitoring Committee; Current; Amgen Inc. L.R. Azoulay: Consultant; Current; Roche Diagnostics. Consultant; Ended; Boehringer Ingelheim International GmbH. E. Patorno: Research Support; Current; Boehringer Ingelheim International GmbH, AstraZeneca, Bayer AG, National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute. Other - Royalties; Current; UpToDate. Funding Patient Centered Outcomes Research Institute (DB-2020C2-20326)