The following is a summary of “Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial,” published in the June 2023 issue of Gastroenterology & Hepatology by Loomba et al.
Individuals diagnosed with non-alcoholic steatohepatitis (NASH)-associated cirrhosis are susceptible to elevated rates of morbidity and mortality, specifically related to the liver and general. Researchers conducted a study to assess the effectiveness and safety of the glucagon-like peptide-1 analog, semaglutide, in individuals diagnosed with non-alcoholic steatohepatitis (NASH) and compensated cirrhosis. This double-masked, placebo-controlled phase 2 trial recruited patients from 38 medical centers in the United States. Adult individuals diagnosed with biopsy-confirmed non-alcoholic steatohepatitis (NASH)-related cirrhosis and a body-mass index (BMI) of 27 kg/M2 or higher were randomly allocated in a ratio of 2:1 to receive either a once-weekly subcutaneous dose of semaglutide 2·4 mg or a visually identical placebo. The participants were assigned in a random manner using an interactive web response system, with stratification based on the presence or absence of type 2 diabetes. The patients, investigators, and outcome assessors were blinded to the treatment allocation.
The primary outcome measure was the percentage of patients exhibiting a progression of liver fibrosis by at least one stage or more, without any deterioration of nonalcoholic steatohepatitis (NASH) after 48 weeks. This was evaluated through biopsy in the intention-to-treat population. Safety was assessed in all patients who received at least one administration of the investigational medication. The clinical trial has concluded, completed, and duly registered with ClinicalTrials.gov under the identification number NCT03987451. About 71 individuals were recorded for the study from June 18, 2019, to April 22, 2021. Among them, 49 (69%) were identified as female, while 22 (31%) were identified as male. The study participants exhibited a mean age of 59·5 years (standard deviation [SD] 8·0) and a mean body mass index (BMI) of 34·9 kg/M2 (SD 5·9). Among the patients, 53 (75%) had diabetes. 47 individuals were randomly allocated to the semaglutide cohort, while 24 were assigned to the placebo cohort.
After 48 weeks, there was no statistically significant disparity between the two cohorts in the percentage of patients exhibiting an enhancement in hepatic fibrosis of one stage or more without deterioration of non-alcoholic steatohepatitis (NASH) (five [11%] out of 47 patients in the semaglutide cohort versus seven [29%] out of 24 in the placebo cohort; odds ratio 0·28 [95% CI 0·06–1·24; P=0·087). Additionally, no statistically significant variation was observed between the groups regarding the percentage of patients who attained NASH resolution (P=0.29). Comparable rates of patients in both groups experienced adverse events (42 [89%] patients in the semaglutide group vs. 19 [79%] in the placebo group) and serious adverse events (six [13%] vs. two [8%]). The most prevalent adverse events reported were nausea (21 [45%] compared to four [17%]), diarrhea (nine [19%] compared to two [8%]), and vomiting (eight [17%] compared to none). The hepatic and renal function exhibited no significant changes and remained stable. There were no instances of decompensation or fatalities. In individuals diagnosed with non-alcoholic steatohepatitis (NASH) and compensated cirrhosis, the administration of semaglutide did not yield significant improvements in fibrosis or the attainment of NASH resolution compared to a placebo. There were no newly identified safety concerns reported.