Treatment with semaglutide was found to result in a significantly higher percentage of nonalcoholic steatohepatitis (NASH) resolution vs placebo, according to findings from a phase 2 study published in the New England Journal of Medicine. There was no significant difference in the rate of patients who experienced an improvement in fibrosis stage, the study authors said.
NASH is associated with increased morbidity and mortality; however, treatment options are limited. The efficacy and safety of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide in patients with NASH is unknown. Therefore, researchers conducted a 72-week, double-blind phase 2 trial involving 320 patients with biopsy-confirmed NASH and liver fibrosis (230 of whom had stage F2 or F3 fibrosis) who were randomly assigned to receive semaglutide at a dose of 0.1 mg (n=80), 0.2 mg (n=78), or 0.4 mg (n=82). Eighty patients received placebo.
The study authors found that the percentage of patients in whom NASH resolution was achieved with no worsening of fibrosis was 40% in the 0.1 mg group, 36% in the 0.2 mg group, 59% in the 0.4 mg group, and 17% in the placebo group (P <.001 for semaglutide 0.4 mg vs placebo). The odds ratios for NASH resolution without worsening of fibrosis were 3.36, 2.71. and 6.87 when the 0.1 mg, 0.2 mg, and 0.4 mg doses of semaglutide were compared with placebo.
An improvement in liver fibrosis stage occurred in 43% of the patients in the 0.4 mg group and in 33% of the patients in the placebo group (P =.48). Thirty-two percent and 49% of patients in the 0.2 mg and 0.1 mg groups also experienced an improvement in fibrosis stage with no worsening of NASH, respectively.
The mean percent weight loss was 13% in the 0.4-mg group and 1% in the placebo group. The incidence of nausea (42% vs 11%), constipation (22% vs 12%), decreased appetite (22% vs 5%), and vomiting (15% vs 2%) was higher in the 0.4-mg group than in the placebo group.
“Serious adverse events were reported in a higher percentage of patients in the semaglutide groups (15% to 19% across dose groups) than in the placebo group (10%), but there was no apparent dose-dependent relationship,” the investigators said.
Overall, neoplasms (benign, malignant, or unspecified), including cysts and polyps, were reported in 15% of patients in the semaglutide groups and in 8% of patients in the placebo group.
The findings indicate that semaglutide is a viable treatment strategy in this patient population, according to the study authors. “Among patients with biopsy-confirmed NASH and fibrosis, a significantly higher percentage of patients had NASH resolution with once-daily semaglutide than with placebo,” they concluded.
Disclosure: This clinical trial was supported by Novo Nordisk. Please see the original reference for a full list of the authors’ disclosures.
Newsome PN, Buchholtz K, Cusi K, et al; NN9931-4296 Investigators. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. Published online November 13, 2020. doi:10.1056/NEJMoa2028395