Tirzepatide for metabolic dysfunction and steatohepatitis associated with liver fibrosis
Background
The steatohepatitis associated with metabolic dysfunction (MASH) is a progressive liver disease associated with liver-related complications and death. The efficacy and safety of tirzepatidean agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, in patients with MASH and moderate or severe fibrosis.
Methods
We carried out a test of Phase 2a multicenter, double-blind, randomized, placebo-controlled, dose-finding 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. The primary endpoint was resolution of MASH without worsening fibrosis at 52 weeks. A key secondary endpoint was an improvement (decrease) of at least one stage of fibrosis without worsening of MASH.
Results
Among the 190 participants who had undergone randomization, 157 had liver biopsy results at week 52 that could be evaluated, and missing values were imputed under the assumption that they would follow the pattern of results in the placebo group.
The percentage of participants who met criteria for resolution of MASH without worsening fibrosis was 10% in the placebo group, 44% in the tirzepatide 5 mg group (difference versus placebo, 34 percentage points; range trust [IC] 95%). , 17 to 50), 56% in the tirzepatide 10 mg group (difference, 46 percentage points; 95% CI, 29 to 62), and 62% in the tirzepatide 15 mg group (difference, 53 percentage points; 95% CI, 37 to 69) (P
