Tirzepatide for Metabolic Dysfunction–Associated Steatohepatitis (MASH) & Uptick in GLP1 Use

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R Loomba et al. NEJM 2024; 391; 299-310. Tirzepatide for Metabolic Dysfunction–Associated Steatohepatitis with Liver Fibrosis

F Kanwal. N Engl J Med 2024;391:371-372. Dual Agonists for Management of Metabolic Dysfunction–Associated Steatohepatitis (Associated editorial)

Background: The efficacy and safety of tirzepatide, an agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, in patients with MASH and moderate or severe fibrosis is unclear.

Methods: This was a phase 2, dose-finding, multicenter, double-blind, randomized, placebo-controlled trial involving participants with biopsy-confirmed MASH and stage F2 or F3 (moderate or severe) fibrosis. Participants were randomly assigned to receive once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 52 weeks. 

My take: Until very recently, there were no effective pharmacologic agents for steatotic liver disease (SLD). Now it appears that there will be multiple effective agents. When newer agents for hepatitis C became available (Harvoni was FDA approved 10 years ago), there were concerns about the high cost. With SLD, this is an even bigger concern give the indefinite treatment period.

From editorial: “Overall, these data are encouraging. Clinicians providing care for patients with MASH will probably have an increasing number of options in their armamentarium. With a growing menu of effective treatments, harms and unacceptable side effects will be important considerations in making treatment decisions.”

Related blog posts:

ACG Review (Zobair Younassi, MD): NAFLD and NASH

Related article: YH Yeo et al. Annals of Intern Med 2024; https://doi.org/10.7326/M24-00. Shifting Trends in the Indication of Glucagon-like Peptide-1 Receptor Agonist Prescriptions: A Nationwide Analysis