Semaglutide, manufactured by Novo Nordisk under the brand names Ozempic, Wegovy, and Rybelsus, is FDA-approved for type 2 diabetes and obesity patients. Additionally, it has been tested for other diseases, such as heart and renal diseases. In a recent publication in the NEJM journal, Novo Nordisk released its interim data on the phase 3 trial of semaglutide on MASH (Metabolic Dysfunction Associated Steatohepatitis) patients. MASH is a progressive liver disease with no treatment and poor survival. In 2024, Rezdiffera from Madrigel Pharmaceuticals was the first medicine approved by the FDA for MASH. The details of Rezdiffera’s phase 3 clinical trial can be found here. The following are the details of semaglutide efficacy on MASH steatohepatitis and fibrosis.
Study details:
1197 patients with MASH and fibrosis stage 2 or 3 were recruited and randomized in a 2:1 ratio of semaglutide or placebo for 240 weeks. In this interim analysis of 72 weeks, data from 800 patients were reported. Semaglutide was given at a dose of 2.4mg in a dose escalation manner, starting from 0.25mg once weekly subcutaneously and increasing to 0.5 mg, 1 mg, 1.7 mg, and 2.4 mg every four weeks.
Primary endpoint outcome:
- 62.9% of patients with semaglutide vs 34.3% of placebo group (difference of 28.7%, 95% CI, 21.1 to 36.2, P<0.001) showed improvement in steatohepatitis without worsening of fibrosis.
- 36.8% in semaglutide vs 22.4% in placebo (14.4% difference, 95% CI, 75 to 21.3; P<0.001) showed a reduction in liver fibrosis score without worsening of steatohepatitis.
Secondary endpoint outcome:
- 32.7% of semaglutide vs 16.1% in placebo reported combined resolution of steatohepatitis and reduction in liver fibrosis (difference of 16.5%; 95% CI, 10.2 to 22.8; P<0.001).
- Mean change in body weight was -10.5% in the semaglutide group vs -2% in the placebo (difference of -8.5%, 95% CI, -9.6 to -7.4; P<0.001).
- The mean change in bodily pain score was not statistically different.
Safety
88% of semaglutide patients maintained the target dose of 2.4 mg until 72 weeks. 86.3% of semaglutide and 79.7% of placebo patients reported an adverse event. Adverse events leading to trial discontinuation occur in 2.6% of semaglutide patients vs 3.3% in placebo. The most common adverse events were gastrointestinal for both groups such as nausea, diarrhea, constipation, and vomiting.
Limitations of the study
- Small number of Black patients.
- Lack of data on biomarkers of alcohol consumption, genetic polymorphisms as a determinant of therapeutic response, and change in body composition during the therapy.
- The number of lean patients was too few to make any definitive conclusion.
Dr. Vinny Negi, Ph.D,
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