1701-P: Longitudinal Dynamics of Cardiometabolic Parameters in a MASH Population Stratified by Baseline Glycemia and Treated with Semaglutide: Post Hoc Insights from the ESSENCE Trial Part 1

Introduction and Objective: In the ESSENCE trial (NCT04822181), semaglutide 2.4 mg improved HbA1c regardless of baseline glycemia level. We explored dynamic changes in HbA1c, other cardiometabolic risk factors (CMRFs), and liver health parameters across different glycemia-level subgroups. Methods: Post hoc analysis of the first 800 participants randomized to semaglutide or placebo. Groups: nondiabetes, prediabetes, type 2 diabetes. CMRFs (HbA1c, body weight BW, waist-to-height ratio WtHR, systolic and diastolic blood pressure BP, triglycerides, non-HDL cholesterol, hsCRP) and liver health parameters (ALT, controlled attenuation parameter, Enhanced Liver Fibrosis, FibroScan-AST, liver stiffness measurement) were assessed up to week 72. Results: Regarding semaglutide treatment up to week 72 and across all glycemia-level subgroups, BW and WtHR steadily decreased. HbA1c, BP, triglycerides, non-HDL, and hsCRP improved (Figure). By contrast, shifts in these CMRFs were negligible with placebo. All liver health parameters improved with semaglutide treatment; changes were minimal with placebo (Figure). Conclusion: Semaglutide resulted in progressive and consistent improvement in CMRFs and liver health parameters versus placebo regardless of baseline glycemia level in people with MASH and liver fibrosis. Disclosure M. Rinella: Consultant; Current; 89bio, Inc., Lilly, Novo Nordisk, Madrigal Pharmaceuticals, Inc., Regeneron Pharmaceuticals Inc., GlaxoSmithKline plc., Boehringer Ingelheim International GmbH, Altimmune, Akero Therapeutics, Inc. Other - this is an error. cannot remove. Also could not add Akero and Echosens to disclosures; Current; Gan Ended; Novo Nordisk, Merck Sharp Ended; Eli Lilly and Company, Merck Sharp Current; Boehringer Ingelheim International GmbH, Boston Therapeutics, Inc. Advisory Panel; Ended; Gilead Sciences, Inc. Advisory Panel; Current; Echosens, Madrigal Pharmaceuticals, Inc., Merck Ended; Pfizer Inc. Advisory Panel; Current; Siemens, GSK. Speaker's Bureau; Current; AstraZeneca, Boehringer Ingelheim International GmbH, Echosens, Madrigal Pharmaceuticals, Inc., Novo Nordisk. Advisory Panel; Current; Sagimet. N.M. Eklöf: Employee; Current; Novo Nordisk A/S. W. Kim: None. N.M. Krarup: Employee; Current; Novo Nordisk. B. Ludvik: Advisory Panel; Current; Novo Nordisk. Research Support; Current; Novo Nordisk. Speaker's Bureau; Current; Novo Nordisk. Advisory Panel; Current; Boehringer Ingelheim International GmbH. Research Support; Current; Boehringer Ingelheim International GmbH. Speaker's Bureau; Current; Boehringer Ingelheim International GmbH. Advisory Panel; Current; Eli Lilly and Company. Research Support; Current; Eli Lilly and Company. Speaker's Bureau; Current; Eli Lilly and Company. Research Support; Current; Amgen Inc. P.N. Newsome: Speaker's Bureau; Current; Novo Nordisk, Ipsen Biopharmaceuticals, Inc. Consultant; Current; Akero Therapeutics, Inc. Speaker's Bureau; Current; Echosens. Consultant; Current; Aligos, Boehringer Ingelheim International GmbH, Forth Therapeutics, Inventiva Pharma, Sagimet, Madrigal Pharmaceuticals, Inc., Novo Nordisk, 89bio, Inc., UCB, Inc. V. Ratziu: Consultant; Current; Novo Nordisk, Boehringer Ingelheim International GmbH, GlaxoSmithKline plc., Akero Therapeutics, Inc., 89bio, Inc. A. Sanyal: Consultant; Current; Eli Lilly and Company, Abbott, GENFIT, Corcept Therapeutics, Arrowhead Pharmaceuticals, Inc., Alnylam Pharmaceuticals, Inc., Boehringer Ingelheim International GmbH, Genentech, Inc., Gilead Sciences, Inc., Gilead Sciences, Inc., Lipocine Inc., Madrigal Pharmaceuticals, Inc., Merck Current; AstraZeneca. Consultant; Current; AstraZeneca. Other - Institution has received grant support; Current; Bristol-Myers Squibb Company. Consultant; Current; Bristol-Myers Squibb Company. Other - Institution has received grant support; Current; Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Novartis AG. Other - Royalties; Current; Elsevier, UpToDate. Stock/Shareholder; Current; DURECT Corporation. A. Trifan: Consultant; Ended; Lilly Global Health Partnership, Novo Nordisk Foundation. Research Support; Ended; AbbVie Inc., Gilead Sciences, Inc. T. Vestergaard: Employee; Current; Novo Nordisk. M. Roden: Advisory Panel; Current; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Madrigal Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Echosens.