A phase 2 trial found that 62% of patients receiving 15 mg of tirzepatide achieved resolution of metabolic dysfunction–associated steatohepatitis without worsening fibrosis, compared to 10% in the placebo group, with resolution rates of 44% and 56% in the 5 mg and 10 mg groups, respectively (P<.001 for all comparisons).
The study, published in The New England Journal of Medicine, evaluated the efficacy and safety of tirzepatide, a dual agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, in 190 patients with biopsy-confirmed metabolic dysfunction–associated steatohepatitis (MASH) and moderate to severe fibrosis (F2 or F3).
Patients were randomized to receive once-weekly subcutaneous injections of tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 52 weeks. The primary endpoint was achieving resolution of MASH without worsening fibrosis. Secondary endpoints included improvement in fibrosis stage without worsening MASH.
Improvement in fibrosis without worsening MASH was observed in 55% of patients in the 5 mg tirzepatide group and 51% in both the 10 mg and 15 mg groups, compared to 30% in the placebo group.
The most common adverse events reported were mild to moderate gastrointestinal issues. Tirzepatide was well tolerated, with no new safety concerns identified.
Investigators found that the 52-week treatment with tirzepatide led to more frequent resolution of MASH without worsening fibrosis compared to placebo in patients with moderate or severe fibrosis. Further research with larger and longer trials is necessary to better understand tirzepatide's efficacy and safety for treating MASH.
The study was funded by Eli Lilly.