OSA occurs more frequently in obese persons and in those with type 2 diabetes (T2D) and is linked to increased risk of cardiovascular disease (CVD). This post-hoc analysis of EMPA-REG OUTCOME investigated the baseline (BL) prevalence of investigator-reported OSA; explored the effects of the empagliflozin (EMPA) vs. placebo (PBO) on metabolic parameters in patients with OSA; and sought to determine its potential effect on incident OSA. OSA at BL was reported in 391/7020 patients with T2D and established CVD (5.6% [PBO 5.4%; EMPA 5.7%]). Those with OSA were more likely to be male (82.9 vs. 70.8%), have moderate to severe obesity (BMI ≥ 35 kg/m2: 55.2% vs. 18.2%; mean weight 105.5 vs. 85.2 kg), and have greater prevalence of coronary artery disease (88.0 vs. 74.9%) at BL. Over a median 3.1 years, EMPA had similar PBO-adjusted reductions in HbA1c, waist circumference and systolic blood pressure regardless of OSA status at BL. However, EMPA had a larger effect on weight reduction in patients with OSA (week 28 adjusted mean (±SE) difference vs. PBO from BL: -2.9±0.4 vs. -1.9±0.1 kg in those without OSA and at week 52: -2.9±0.5 vs. -1.9 kg ±0.1, respectively). During follow-up, fifty patients developed new-onset OSA (Figure) and EMPA reduced this risk by 52% (HR 0.48 [95% CI 0.27, 0.83]). In conclusion, EMPA induces favorable metabolic effects in patients with OSA and T2D/CVD and may reduce new-onset OSA. Disclosure I.J. Neeland: None. B. Eliasson: Consultant; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. T. Kasai: Other Relationship; Self; Fukuda Denshi, Philips Respironics, ResMed. N. Marx: Other Relationship; Self; Amgen, AstraZeneca, Bayer Vital, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Kowa Research Institute, Inc., Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. 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. 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. 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. I. Zwiener: Employee; Self; Boehringer Ingelheim International GmbH. B.S. Wojeck: None. H.K. Yaggi: None. O. Johansen: Employee; Self; Boehringer Ingelheim International GmbH. Funding Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance