Sodium glucose co-transporter 2 inhibitors (SGLT2i) are indicated for treatment of T2DM; some SGLT2i have reported a CV benefit and some reported a risk of BKA. U.S. claims databases were analyzed using a prespecified protocol to examine CANA-associated effects on BKA and hospitalization for heart failure (HHF) vs. other SGLT2i and non-SGLT2i. Analyses used a propensity score adjusted new user design with numerous sensitivity analyses. The 4 databases included 142K new users of CANA, 110K of other SGLT2i, and 460K of non-SGLT2i AHAs. Meta-analysis results are reported when heterogeneity across databases was not substantial (I2 <0.4). There was no evidence of increased risk of BKA with CANA vs. non-SGLT2i or other SGLT2i in on-treatment or ITT analyses (Table). HHF benefits were demonstrated in these analyses, consistent with clinical trials. Similar BKA and HHF results were seen in a subgroup with established CV disease. In this large comprehensive analysis, neither CANA nor other SGLT2i showed an increased risk of amputation vs. non-SGLT2i. Because on-treatment median exposure was <6 months, future observational studies with longer duration are needed. This study helps to further characterize the potential benefits and harms of SGLT2i as observed in routine clinical practice to complement the evidence from clinical trials and prior observational studies.

P. Ryan: Employee; Self; Janssen Research & Development, LLC. J.B. Buse: Other Relationship; Self; ADOCIA, AstraZeneca, Dexcom, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Fractyl Laboratories, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Metavention, NovaTarg, Novo Nordisk A/S, Sanofi, VTV Therapeutics. Research Support; Self; Boehringer Ingelheim GmbH, Johnson & Johnson Services, Inc., Theracos, Inc.. Other Relationship; Self; Shenzhen Hightide Biopharmaceutical, Ltd.. Research Support; Self; National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association. Research Support; Self; Patient-Centered Outcomes Research Institute. Other Relationship; Self; National Institute of Environmental Health Sciences. M. Schuemie: Employee; Self; Janssen Research & Development, LLC. F. Defalco: Employee; Self; Janssen Research & Development, LLC. Z. Yuan: Employee; Self; Janssen Research & Development, LLC. P. Stang: Employee; Self; Janssen Research & Development, LLC. J.A. Berlin: Employee; Self; Johnson & Johnson, LLC. N. Rosenthal: Employee; Self; Janssen Research & Development.

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