Background: Current guidelines support aggressive LDL-C lowering in patients with diabetes. We assessed the efficacy and safety of BA, a first-in-class ATP-citrate lyase inhibitor, by baseline glycemic status (diabetes, prediabetes, or normoglycemia) in patients with hypercholesterolemia. Methods: Four phase 3 trials randomized 3623 patients on stable lipid-lowering therapy to receive BA 180 mg or placebo (PBO) once daily for 12 to 52 weeks. Studies were grouped into 2 pools by enrollment criteria (52-weeks in patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia vs. 12- or 24- weeks in patients with statin intolerance). Primary efficacy endpoint was percent change from baseline to week 12 in LDL-C. Results: In both pools, BA significantly lowered LDL-C compared with PBO, regardless of baseline glycemic status (all P<.001; Table). Significant reductions with BA vs. PBO were seen in total cholesterol, non-HDL-C, apolipoprotein B, and hsCRP (all P<.01). The safety profile of BA was similar to PBO and did not vary by glycemic status. BA did not worsen measures of glycemic control or increase occurrence of new-onset diabetes mellitus compared with PBO. Conclusion: BA significantly lowered LDL-C and had a safety profile comparable to PBO, regardless of baseline glycemic status. Disclosure L.A. Leiter: Advisory Panel; Self; Abbott, Amgen, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi, Servier. Research Support; Self; Amgen, AstraZeneca, Kowa Pharmaceuticals America, Inc., Medicines Company. Speaker’s Bureau; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Medscape, Merck & Co., Inc., Novo Nordisk Inc., Sanofi, Servier. M. Banach: Advisory Panel; Self; Esperion Therapeutics, Inc., Novo Nordisk Inc. Research Support; Self; Resverlogix Corp. Speaker’s Bureau; Self; Amgen, Sanofi. A.L. Catapano: Other Relationship; Self; Akcea Therapeutics, Amgen, Daiichi Sankyo, Esperion Therapeutics, Inc., Kowa Company, Ltd., Menarini Group, Mylan, Novartis, Ionis Pharmaceuticals, Medco, MSD, Recordati, Astrazeneca, Aegerion, Amryt, Eli Lilly, Genzyme, Regeneron Pharmaceuticals, Sanofi. P. Duell: Consultant; Self; Akcea Therapeutics, AstraZeneca, Esperion Therapeutics, Inc. Other Relationship; Self; Regeneron Pharmaceuticals, REGENXBIO Inc., Retrophin, Inc. A. Gotto: Board Member; Self; Esperion Therapeutics, Inc. Consultant; Self; Amarin Corporation, Kowa Company, Ltd. Other Relationship; Self; Ionis Pharmaceuticals, Inc. U. Laufs: Advisory Panel; Self; Esperion Therapeutics, Inc. G. Mancini: Advisory Panel; Self; Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Boehringer Ingelheim (Canada) Ltd., Esperion Therapeutics, Inc., HLS Therapeutics, Inc., Sanofi. K.K. Ray: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Esperion Therapeutics, Inc., Novo Nordisk Inc., Sanofi. J.C. Hanselman: Employee; Self; Esperion Therapeutics, Inc. Stock/Shareholder; Self; Esperion Therapeutics, Inc. A. Feng: Employee; Self; Esperion Therapeutics, Inc. H. Bays: Advisory Panel; Self; Esperion Therapeutics, Inc. Consultant; Self; Kowa Company, Ltd. Research Support; Self; Abbott, Acasti, Akcea, Amarin Corporation, Amgen, AstraZeneca, Dr. Reddy’s Laboratories, Esperion Therapeutics, Inc., Gan & Lee Pharmaceuticals, Ionis Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Johnson & Johnson, LIB, Lilly Diabetes, Matinas BioPharma, Medicines Company, MedImmune, Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Regeneron Pharmaceuticals, Sanofi.