This was a 72-week, double-blind phase 2 randomized controlled trial involving patients with histologically proven non-alcoholic steatohepatitis (NASH) with non-alcoholic fatty liver disease (NAFLD) activity score >=4 and F1-F3 fibrosis. Three hundred and twenty patients with (62) or without (38) diabetes mellitus (DM) wererandomizedtoreceivedaily subcutaneous injectionofsemaglutide at a dose of 0.1 mg(n=80), 0.2 mg(n=78) or 0.4 mg(n=82) or placebo (n=80 patients). The primary end-point of resolution of NASH without worsening of fibrosis was observed in a significantly higher proportion of those who received 0.4 mg of semaglutide (59) compared to placebo (17, p<0.001); the highest efficacy ever shown by any drug in resolution of NASH. However, there was no difference in the attainment of the secondary end-point of improvement in fibrosis by atleastone stage without worsening ofNASH between the semaglutide arm and placebo. Semaglutide was also associated with a dose-dependent reduction in body weight ranging from 5 to 13 in those who received 0.1 and 0.4 mg, respectively. In comparison, the average weight loss in the placebo arm was only 1 . Importantly, the decrease in body weight, which was observed in the initial 28-44 weeks of semaglutide therapy, was sustained over the remaining duration of the study. Overall, semaglutide was well tolerated. The most commonadverse effects with semaglutide includedgastrointestinal disturbances such as nausea, vomiting, anorexia, constipation and abdominal pain, which led to drug discontinuation in 4 of patients. However, overall drug discontinuation rates were comparable between semaglutide (7) and placebo (5). Although an increase in serum amy lase and lipase was observed in those receiving semaglutide, there was no incidence of acute pancreatitis. Three patients developed malignancies during the study, all of whom were receiving semaglutide.
展开▼
