According to new phase 2 trial results, Once-weekly semaglutide 2.4 mg fails to significantly improve fibrosis or achieve resolution of non-alcoholic steatohepatitis (NASH) versus placebo in patients with NASH-related compensated cirrhosis.
Patients with non-alcoholic steatohepatitis (NASH)-related cirrhosis are at high risk of liver-related and all-cause morbidity and mortality. We investigated the efficacy and safety of the glucagon-like peptide-1 analogue semaglutide in patients with NASH and compensated cirrhosis.
This double-blind, placebo-controlled phase 2 trial enrolled patients from 38 centres in Europe and the USA. Adults with biopsy-confirmed NASH-related cirrhosis and body-mass index (BMI) of 27 kg/m2 or more were randomly assigned (2:1) to receive either once-weekly subcutaneous semaglutide 2·4 mg or visually matching placebo. Patients were randomly allocated via an interactive web response system, stratified by presence or absence of type 2 diabetes. Patients, investigators, and those assessing outcomes were masked to treatment assignment. The primary endpoint was the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH after 48 weeks, assessed by biopsy in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug. Findings
• 71 patients were enrolled between June 18, 2019, and April 22, 2021; 49 (69%) patients were female and 22 (31%) were male.
• Patients had a mean age of 59·5 years (SD 8·0) and mean BMI of 34·9 kg/m2 (SD 5·9); 53 (75%) patients had diabetes.
• 47 patients were randomly assigned to the semaglutide group and 24 to the placebo group. After 48 weeks, there was no statistically significant difference between the two groups in the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH • There was also no significant difference between groups in the proportion of patients who achieved NASH resolution (p=0·29).
• Similar proportions of patients in each group reported adverse events and serious adverse events
• The most common adverse events were nausea
• Hepatic and renal function remained stable. There were no decompensating events or deaths.
In patients with NASH and compensated cirrhosis, semaglutide did not significantly improve fibrosis or achievement of NASH resolution versus placebo. No new safety concerns were raised. Reference:
Prof Rohit Loomba, Prof Manal F Abdelmalek, Matthew J Armstrong, Maximilian Jara, Mette Skalshøi Kjær, Niels Krarup, et al. Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. The Lancet Gastroenterology & Hepatology. Published:March 16, 2023DOI:https://doi.org/10.1016/S2468-1253(23)00068-7
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