Introduction and Objective: T2D increases the risk of clinical outcomes in MASH cirrhosis. This post hoc analysis assessed changes in liver disease and insulin sensitivity in participants with baseline T2D and compensated cirrhosis due to MASH in the SYMMETRY trial of efruxifermin.Methods: SYMMETRY (NCT05039450) is a phase 2b, randomized, placebo-controlled trial that evaluated efruxifermin QW vs placebo for 96 weeks. In participants with baseline T2D, we evaluated the proportion with ≥1-stage fibrosis improvement without MASH worsening (primary endpoint) and markers of liver injury and fibrosis, insulin sensitivity, and lipids.Results: Baseline characteristics of participants with T2D (N=145): 73% female, mean ±SD age 61 ±8 years, HbA1c 7.0 ±1.1%, ELF 10.5 ±0.8, LSM 24 ±13 kPa, BMI 36 ±7 kg/m2. Statistical or numerical improvements were observed for efruxifermin vs placebo in measures of fibrosis (primary endpoint, ELF, LSM), liver injury (ALT, AST), insulin sensitivity (HOMA-IR, adiponectin, C-peptide), and lipids (HDL-C, non-HDL-C, triglycerides) (Table).Conclusion: In this post hoc analysis, efruxifermin was associated with improvements in markers of liver disease and insulin sensitivity in individuals with T2D and MASH cirrhosis. Phase 3 trials of efruxifermin in MASH are ongoing.
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 & Co., Inc., GlaxoSmithKline plc., Novartis AG, Novo Nordisk, Pfizer Inc., Salix Pharmaceuticals, Sequana Medical NV, Takeda Pharmaceutical Company Limited. Other – Institution has received grant support; 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. 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 & Lee Pharmaceuticals. D. Chan: Employee; Current; Akero Therapeutics, Inc. S.K. Billes: Employee; Current; Akero Therapeutics, a Novo Nordisk Company. Stock/Shareholder; Current; Novo Nordisk. A. Zari: Employee; Current; Akero Therapeutics, Inc. T. Rolph: Employee; Current; Akero Therapeutics, Inc. Stock/Shareholder; Current; Bioage. M. Noureddin: Advisory Panel; Current; Akero Therapeutics, a Novo Nordisk company, Altimmune, Alligos, AstraZeneca, Biogen, Boston Pharmaceuticals, Curve bioscience, Daiichi Sankyo, GlaxoSmithKline plc., HistoIndex, Kriya Therapeutics, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Neuraly Inc., Novo Nordisk, OPKO Health, Rivus, Sagimet, Takeda Pharmaceutical Company Limited. Research Support; Current; Allergan, Altimmune, Akero Therapeutics, a Novo Nordisk company, Biogen, Bristol-Myers Squibb Company, Boston Pharmaceuticals, Conatus, Corcept Therapeutics, Gilead Sciences, Inc., Galectin, GENFIT, GlaxoSmithKline plc., Kowa Pharmaceuticals America, Inc., Enanta, Madrigal Pharmaceuticals, Inc., Lilly, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Rivus, Shire plc., Takeda Pharmaceutical Company Limited, Terns, Viking Therapeutics, Zydus. Stock/Shareholder; Current; OPKO Health, Kriya Therapeutics, Akero Therapeutics, Inc. Speaker’s Bureau; Current; Madrigal Pharmaceuticals, Inc., Novo Nordisk.
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