Diabetes care

Metabolic and Liver Tissue Changes in People with Fatty Liver Disease With and Without Type 2 Diabetes Treated with Tirzepatide

Updated

Abstract

Participants with MASH who responded to tirzepatide experienced a 16.0% reduction in body weight compared to a 7.0% reduction in nonresponders.

  • Greater body weight reductions were associated with both MASH resolution and fibrosis improvement.
  • MASH responders had a reduction in HbA1c of -1.2%, while nonresponders had a reduction of -0.6%.
  • MASH responders showed significant improvements in liver fat and insulin sensitivity measures compared to nonresponders.
  • Normalization of liver fat was identified as a significant factor mediating both MASH resolution and fibrosis improvement.

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Funding

Competing interests

Duality of Interest. C.C. has received grant support from Echosens, Gilead, and Novo Nordisk; consulting fees from Gilead, Novo Nordisk, AstraZeneca, Eli Lilly and Company, E-Scopics, MSD, Bayer, and Echosens; honoraria from Madrigal, Novo Nordisk, and Echosens; and travel support from AstraZeneca. K.C. has received grant support from Boehringer Ingelheim, Echosens, Inventiva, LabCorp, Perspectum, and Target-NASH (research support to the University of Florida); and consulting fees from Arrowhead, 89Bio, Boehringer Ingelheim, Bristol-Myers Squibb, Echosens, Eli Lilly and Company, GSK, MGGM Therapeutics LLC, Novo Nordisk, Sagimet Biosciences, Terns Pharmaceuticals, and Zealand Pharma. J.R. has received clinical research grants from Amgen, Applied Therapeutics, AstraZeneca, Biomea Fusion, BioAge, Boehringer Ingelheim, Carmot, Corcept, Eli Lilly and Company, Hanmi, Merck, Novartis, Novo Nordisk, Oramed, Pfizer, Regeneron, and Sanofi; scientific advisory board honorarium or consulting fees from Amgen, Applied Therapeutics, Biomea Fusion, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Novo Nordisk, Oramed, Regeneron, Roche, Sanofi, Structure Therapeutics, Terns Pharmaceuticals, and Zealand Pharma; and honoraria from Eli Lilly and Company, and Sanofi. E.B. has received consulting fees from Boehringer, Eli Lilly and Company, Novo Nordisk, and Madrigal; honoraria from MSD, Boehringer Ingelheim, and Madrigal; and participated on advisory boards for Novo Nordisk, Boehringer, and Eli Lilly and Company. M.K.T. is a steering committee member for Accelerating Medicines Partnership–Common Metabolic Diseases and is an employee and shareholder of Eli Lilly and Company. R.L. has received grant support from Arrowhead Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes, and Terns Pharmaceuticals; consulting fees from Aardvark Therapeutics, Altimmune, Arrowhead Pharmaceuticals, AstraZeneca, Cascade Pharmaceuticals, Eli Lilly and Company, Gilead, Glympse Bio (now Sunbird Bio), Inipharma, Intercept, Inventiva, Ionis, Janssen, Lipidio, Madrigal, Neurobo, Novo Nordisk, Merck, Pfizer, Sagimet, 89bio, Takeda, Terns Pharmaceuticals, and Viking Therapeutics; shareholder of Sagimet Biosciences; and cofounder of LipoNexus, Inc. A.J.S. has received grant support from Boehringer Ingelheim, Echosens North America, Inc., Eli Lilly and Company, Gilead Sciences (Gilead Foundation), Intercept Pharmaceuticals Inc., Mallinckrodt, Merck, Novo Nordisk, Perspectum, Pfizer, Salix Pharmaceuticals, and Zydus; consulting fees from 90bio, Akero, Aligos, Alnylam Pharmaceuticals, Amgen Inc., AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Galmed, Genentech, Gilead Sciences (Gilead Foundation), GlaxoSmithKline, Histoindex, Intercept Pharmaceuticals, Inventiva, Madrigal, Merck, Myovant, NGM Biopharmaceuticals, Northsea, Novartis, Novo Nordisk, Path AI, Pfizer, Poxel, Regeneron Pharmaceuticals, Roche, Salix Pharmaceuticals, Siemens, Surrozen, Takeda Pharmaceuticals America, Target Pharma Solutions, Terns Pharmaceuticals, and Zydus Pharmaceuticals (USA); served on data and safety monitoring committees for Bard Peripheral Vascular, NGM Biopharmaceuticals, and Sequana; is a shareholder of Durect, Exhalenz, Genfit, Hemoshear, Inversago, Northsea, and Tiziana; and received royalties from Elsevier. Y.T., K.J.M., and M.L.H. are employees and shareholders of Eli Lilly and Company. No other potential conflicts of interest relevant to this article were reported.
PubMed

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