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Insulin in T2D is associated with hypoglycemia and weight gain, requires training, can be expensive, and is generally not preferred by patients. Reducing insulin needs is attractive to both patients and practitioners. In EMPA-REG OUTCOME, 7020 patients were treated with empagliflozin (EMPA) 10, 25 mg, or placebo (PBO). Median follow-up was 3.1 yrs. After the first 12 weeks, changes in background glucose-lowering therapy were permitted. We assessed treatment effects of pooled EMPA vs. PBO on time to new initiation of insulin among insulin-naive patients and time to total daily insulin dose increase by >20% among insulin-treated patients. In 3633 (52%) insulin-naive patients, EMPA reduced need for insulin use vs. PBO by 54% (11.1% vs. 22.3%; HR 0.46 [0.39-0.54]), adjusted for key covariates (Figure). In 3387 (48%) patients using insulin at baseline, EMPA reduced need for a >20% increase in insulin dose by 57% (19.1% vs. 36.8%; HR 0.43 [0.37-0.49]). Reductions in incident insulin use was most pronounced in patients within 5 yrs of T2D diagnosis (HR 0.31 [0.21-0.45]) compared with T2D duration of >5-10 yrs (0.42 [0.31-0.59]) or >10 yrs (0.56 [0.44-0.71); Pinteraction =0.03. In patients with T2D and CVD, EMPA markedly and durably delays the need for insulin initiation, more so in those recently diagnosed, and reduces need for large dose increases in those already using insulin. Disclosure M. Vaduganathan: Advisory Panel; Self; Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Relypsa, Inc. Consultant; Self; Amgen, AstraZeneca, Baxter. N. Sattar: Advisory Panel; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Pfizer Inc., Sanofi. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. D.H. Fitchett: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Lilly Diabetes. Other Relationship; Self; Novo Nordisk Inc. A. Ofstad: Employee; Self; Boehringer Ingelheim International GmbH. M. Brueckmann: Employee; Self; Boehringer Ingelheim International GmbH. J.T. George: Employee; Self; Boehringer Ingelheim International GmbH. S. Verma: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Other Relationship; Self; AstraZeneca, AstraZeneca, Bayer AG, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Eli Lilly and Company, EOCI Pharmacomm, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Canada Inc., Novo Nordisk A/S, Novo Nordisk A/S, Sanofi, Sanofi, Sun Pharmaceuticals, Toronto Knowledge Translation Working Group. M. Mattheus: None. C. Wanner: Advisory Panel; Self; Eli Lilly and Company, Merck & Co., Inc., Mundipharma International. Consultant; Self; Boehringer Ingelheim (Canada) Ltd., Sanofi Genzyme. Speaker’s Bureau; Self; AstraZeneca. Other Relationship; Self; Boehringer Ingelheim International GmbH. 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. B. Zinman: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. J. Butler: Consultant; Self; Amgen, Array BioPharma, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, CVRx, G3 Pharmaceuticals, Innolife Co., Ltd., Janssen Pharmaceuticals, Inc., Luitpold Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Relypsa, Inc., VIfor. Funding Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance