Semaglutide Resolves Nonalcoholic steatohepatitis, Finds Study
Nonalcoholic steatohepatitis (NASH) is a common disease that is associated with increased morbidity and mortality, but treatment options are limited. A recent study suggests that treatment with semaglutide resolves NASH with a significantly higher percentage than placebo. The research has been published in The NEW ENGLAND JOURNAL Of MEDICINE on March 25, 2021.
Strong evidence indicates that type 2 Diabetes Mellitus is one of the most important risk factors for faster progression of Nonalcoholic fatty liver disease (NAFLD) to NASH, cirrhosis and hepatocellular carcinoma (HCC). Some previous trials on GLP-1 RAs have also consistently demonstrated that these drugs exert beneficial effects on the histological resolution of NASH. However, there are no approved drugs to specifically treat the NAFLD or NASH. Therefore, Dr Philip N. Newsome, M.B., Ch.B., PhD and his team, conducted a study to assess the efficacy and safety of the glucagon-like peptide-1 receptor agonist semaglutide in patients with NASH.
It was a 72-week, double-blind phase 2 trial involving patients with biopsy-confirmed NASH and liver fibrosis of stage F1, F2, or F3. Researchers randomly assigned 320 patients to receive once-daily subcutaneous 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). The major outcome assessed was the resolution of NASH with no worsening of fibrosis. They also evaluated for improvement of at least one fibrosis stage with no worsening of NASH. The researchers performed these outcomes only in patients with stage F2 or F3 fibrosis; other analyses were performed in all the patients.
Key findings of the study were:
- Upon analysis, the researchers noted 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.
- They also noted an improvement of the fibrosis stage in 43% of the patients in the 0.4-mg group and 33% of the patients in the placebo group.
- They observed a weight loss of 13% in the 0.4-mg group and 1% in the placebo group.
- However, they reported that the incidence of nausea, constipation, and vomiting was higher in the 0.4-mg group than in the placebo group (nausea, 42% vs 11%; constipation, 22% vs 12%; and vomiting, 15% vs 2%).
- They also reported malignant neoplasm in 3 patients who received semaglutide (1%).
- Overall, neoplasms (benign, malignant, or unspecified) were reported in 15% of the patients in the semaglutide groups and 8% in the placebo group with no pattern of occurrence in specific organs.
The authors concluded, "This phase 2 trial involving patients with NASH showed that treatment with semaglutide resulted in a significantly higher percentage of patients with NASH resolution than placebo. However, the trial did not show a significant between-group difference in the percentage of patients with an improvement in the fibrosis stage. "
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