Potential Role of Tirzepatide in Addressing Metabolic Liver Disease and Fibrosis
Tirzepatide, an agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, was assessed for its efficacy and safety in patients with metabolic dysfunction-associated steatohepatitis (MASH) and moderate or severe fibrosis in a phase 2 trial. This study compared various doses of tirzepatide to a placebo over a 52-week period, focusing on the resolution of MASH and improvement in fibrosis stages.
Study Design:
- Participants: 190 participants with biopsy-confirmed MASH and stage F2 or F3 fibrosis.
- Study Type: Phase 2, dose-finding, multicenter, double-blind, randomized, placebo-controlled trial.
- Intervention: Once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 52 weeks.
- Primary Endpoint: Resolution of MASH without worsening of fibrosis at 52 weeks.
- Key Secondary Endpoint: Improvement (decrease) of at least one fibrosis stage without worsening of MASH.
Key Findings:
- Resolution of MASH without worsening of fibrosis:
- Placebo: 10%
- 5 mg tirzepatide: 44% (Difference: 34 percentage points; 95% CI: 17 to 50)
- 10 mg tirzepatide: 56% (Difference: 46 percentage points; 95% CI: 29 to 62)
- 15 mg tirzepatide: 62% (Difference: 53 percentage points; 95% CI: 37 to 69)
- (P<0.001 for all comparisons)
- Improvement of at least one fibrosis stage without worsening of MASH:
- Placebo: 30%
- 5 mg tirzepatide: 55% (Difference: 25 percentage points; 95% CI: 5 to 46)
- 10 mg tirzepatide: 51% (Difference: 22 percentage points; 95% CI: 1 to 42)
- 15 mg tirzepatide: 51% (Difference: 21 percentage points; 95% CI: 1 to 42)
- Adverse Events: Most common in tirzepatide groups were gastrointestinal events, which were mostly mild or moderate in severity.
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HCN Medical Memo
Tirzepatide demonstrated significant efficacy in resolving MASH and improving liver fibrosis stages over a 52-week period compared to placebo. This suggests a potential new therapeutic option for patients with MASH and moderate to severe fibrosis, pending further larger and longer trials to confirm these findings and ensure safety.
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