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Background: At present, dapagliflozin (dapa) is typically used as a 2nd-line glucose-lowering medication (GLM) in T2D, often added to metformin. In DAPA-HF, dapa improved clinical outcomes vs. placebo in patients (pts) with HF and reduced ejection fraction (HFrEF), with or without T2D. We examined whether these benefits varied by background GLM in the T2D cohort, including in drug naive pts and in pts not on metformin. Methods: The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring IV therapy) or cardiovascular death. The effect of dapa vs. placebo was examined using Cox proportional hazards models. Results: Of the 2139 T2D pts, 1596 (75%) were treated with GLM: metformin (48%), insulin (25%), sulfonylurea (21%), DPP-4 inhibitor (14%) and GLP-1 agonist (1%). Drug-naive pts had a lower A1c (6.9%±1.2 vs. 7.5%±1.6; P Conclusion: In DAPA-HF, dapa improved outcomes irrespective of use/no use of GLM or by type of GLM used in pts with T2D and HFrEF. Disclosure K. Docherty: Speaker’s Bureau; Self; Eli Lilly and Company. Other Relationship; Self; AstraZeneca. S.E. Inzucchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Abbott, Merck & Co., Inc., vTv Therapeutics. M.N. Kosiborod: Consultant; Self; Amarin Corporation, Amgen, Applied Therapeutics, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi US, Vifor Pharma Group. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. L. Kober: Speaker’s Bureau; Self; AstraZeneca, Novartis AG. Other Relationship; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. F. Martinez: Board Member; Self; AstraZeneca, Novartis Pharmaceuticals Corporation. O. Bengtsson: Employee; Self; AstraZeneca. D.L. DeMets: Consultant; Self; Actelion Pharmaceuticals US, Inc., AstraZeneca, Boston Scientific, Bristol-Myers Squibb, DalCor Pharmaceuticals, Intercept Pharmaceuticals, Inc., Medtronic. M. Sjostrand: Employee; Self; AstraZeneca. M.S. Sabatine: Consultant; Self; Amgen, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor Pharmaceuticals, Dyrnamix Inc., Esperion Therapeutics, Inc., IFM Therapeutics, Intarcia Therapeutics, Ionis Pharmaceuticals, Inc., Medicines Company, MedImmune, Merck & Co., Inc. Research Support; Self; Amgen, AstraZeneca, Bayer U.S., Daiichi Sankyo, Eisai Inc., Intarcia Therapeutics, Janssen Research and Development, Medicines Company, MedImmune, Merck & Co., Inc., Novartis AG, Pfizer Inc., Quark Pharmaceuticals. S. Solomon: Consultant; Self; AstraZeneca, Theracos, Inc. Research Support; Self; AstraZeneca, Theracos, Inc. P. Jhund: Advisory Panel; Self; Cytokinetics Inc. Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Novartis AG. Other Relationship; Self; AstraZeneca. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Cardurion, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Theracos, Inc.