Nearly 62% achieve MASH resolution without worsening of fibrosis with tirzepatide
Click Here to Manage Email Alerts
Key takeaways:
- More patients on tirzepatide achieved MASH resolution without worsening of fibrosis vs. placebo (43.6% on 5 mg, 55.5% on 10 mg and 62.4% on 15 mg vs. 9.8%).
- In addition, up to 55% achieved improved fibrosis.
Patients with metabolic dysfunction-associated steatohepatitis and advanced fibrosis treated with tirzepatide achieved significant disease resolution without worsening of fibrosis, compared with those on placebo, according to research.
“Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist induced substantial weight reduction in previous placebo-controlled trials in patients with type 2 diabetes and obesity,” Rohit Loomba, MD, MHSc, chief of the division of gastroenterology and hepatology at University of California, San Diego, and director of the MASLD Research Center, said at EASL Congress. “Patients with type 2 diabetes treated with tirzepatide had reduced liver fat and improved biomarkers of MASH and fibrosis.”
In the multicenter, double-blind, placebo-controlled, dose-finding phase 2 SYNERGY-NASH trial, Loomba and colleagues investigated the safety and efficacy of tirzepatide vs. placebo in 190 adult patients (mean age, 54.4 years; 57.4% women; 36.3% Hispanic) with noncirrhotic MASH with stage 2 or 3 fibrosis. More than half (57.4%) had stage 3 fibrosis at baseline.
Patients underwent a baseline liver biopsy and were randomly assigned 1:1:1:1 to once-weekly subcutaneous tirzepatide (5 mg, 10 mg or 15 mg) or placebo for 52 weeks. At week 52, biopsy was repeated.
The primary endpoint was MASH resolution without worsening of fibrosis at 52 weeks, while secondary endpoints included fibrosis improvement by at least one stage without worsening of MASH and reduction in nonalcoholic fatty liver disease activity score (NAS) by two or more points with at least a one-point reduction in two or more NAS components.
According to results, the proportion of patients achieving MASH resolution without worsening of fibrosis was significantly higher in the tirzepatide groups compared with placebo (43.6% with 5 mg, 55.5% with 10 mg and 62.4% with 15 mg vs. 9.8%). Efficacy, based on per-protocol analysis, also significantly favored tirzepatide.
Loomba also reported “significant improvement” of at least one-stage decrease in fibrosis without worsening of MASH, which ranged from 51% to 54.9% in the tirzepatide groups compared with placebo (29.7%). Similarly, reduction in NAS by at least two points was achieved by a significantly greater proportion of tirzepatide-treated patients vs. placebo (range, 71.7% to 78.3% vs. 36.7%).
Further, liver fat content based on MRI-proton density fat fraction was significantly reduced in all tirzepatide groups vs. placebo (range, 45.7% to 57% vs. 9.8%), as were other serum and imaging biomarkers, including liver enzymes, liver inflammation and liver stiffness.
At week 52, body weight significantly decreased between 10.7% and 15.6% with tirzepatide in the overall population. Although patients with type 2 diabetes were “likely to have less weight loss,” Loomba noted, up to 13.7% lost weight with tirzepatide compared with up to 18% without type 2 diabetes.
Adverse events were reported in 92.3% of patients receiving tirzepatide vs. 83.3% with placebo, most commonly gastrointestinal and mild to moderate in severity.
“In the MASH population, the safety profile was generally similar to that observed in phase 2 trials in type 2 diabetes and obesity,” Loomba said. “Larger and longer trials are needed to further assess the efficacy and safety of tirzepatide in MASH.”
Collapse
Loomba R, et al. Tirzepatide for the treatment of metabolic dysfunction-associated steatohepatitis with liver fibrosis: results of the SYNERGY-NASH phase 2 trial. Presented at: EASL Congress; June 5-8,2024; Milan (hybrid meeting).
Click Here to Manage Email Alerts