Semaglutide helps resolve nonalcoholic steatohepatitis

The glucagon-like peptide-1 receptor agonist semaglutide appears safe and effective in the treatment of patients with nonalcoholic steatohepatitis (NASH), resulting in a higher rate of resolution than placebo, according to the results of a phase II trial. There is, however, little effect on fibrosis stage.

A total of 320 patients (mean age, 55 years; 61 percent female) were randomized to receive semaglutide at a dose of 0.1 mg (80 patients), 0.2 mg (78 patients), or 0.4 mg (82 patients) or to receive placebo (80 patients), administered subcutaneously once daily for 72 weeks.

At baseline, most of the patients (62 percent) had type 2 diabetes. The mean body weight was 98.4 kg, and the mean body mass index was 35.8 kg/m². There were 90 patients (28 percent) with stage F1 fibrosis, 72 (22 percent) with stage F2, and 158 (49 percent) with stage F3. The mean activity score for nonalcoholic fatty liver disease was 4.9.

The primary outcome of NASH resolution with no worsening of fibrosis occurred in 40 percent of patients in the 0.1-mg group, 36 percent in the 0.2-mg group, 59 percent in the 0.4-mg group. Only the highest semaglutide dose showed superiority to placebo (17 percent; p<0.001).

There was no significant difference seen in the number of patients whose fibrosis stage improved between the 0.4-mg and placebo groups (43 percent vs 33 percent; p=0.48). The mean percent weight loss was 13 percent and 1 percent, respectively.

In terms of safety, nausea, constipation, and vomiting occurred more frequently in the 0.4-mg than in the placebo group (42 percent vs 11 percent, 22 percent vs 12 percent, and 15 percent vs 2 percent, respectively). Neoplasms (benign, malignant, or unspecified) were documented in 15 percent of the patients on semaglutide and in 8 percent on placebo, with no pattern of occurrence in specific organs seen.