Journal
NEW ENGLAND JOURNAL OF MEDICINE
Volume 384, Issue 12, Pages 1113-1124Publisher
MASSACHUSETTS MEDICAL SOC
DOI: 10.1056/NEJMoa2028395
Keywords
-
Categories
Funding
- Novo Nordisk
- NIHR Birmingham Biomedical Research Centre
- Pharmaxis
- Boehringer Ingelheim
- Cirius Therapeutics
- Novartis
- Echosens
- Poxel
- Zydus
- Inventiva
- Conatus Pharmaceuticals
- Gilead
- Mallinckrodt
- Salix Pharmaceuticals
- Bristol-Myers Squibb
- Merck
- EchoSens-Sandhill Scientific
- Sequana Medical
- Indalo Therapeutics
- Genentech
- Immuron
- Pfizer
- Second Genome
- Tobira Therapeutics-Allergan
- CiVi Biopharma
- Corcept Therapeutics
- CymaBay Therapeutics
- Galectin Therapeutics
- Galmed Pharmaceuticals
- GenFit
- Hepion Pharmaceuticals
- HighTide Therapeutics
- Intercept Pharmaceuticals
- Madrigal Pharmaceuticals
- NGM Biopharmaceuticals
- NorthSea Therapeutics
- Novartis Pharmaceuticals
- Sagimet Biosciences
- ENYO Pharma
- Viking Therapeutics
- Gilead Sciences
- Allergan
- Perspectum
- Fractyl
Ask authors/readers for more resources
This phase 2 trial demonstrated that treatment with semaglutide resulted in a significantly higher percentage of patients with NASH resolution compared to placebo in patients with NASH, but did not show a significant between-group difference in the percentage of patients with an improvement in fibrosis stage.
BACKGROUND Nonalcoholic steatohepatitis (NASH) is a common disease that is associated with increased morbidity and mortality, but treatment options are limited. The efficacy and safety of the glucagon-like peptide-1 receptor agonist semaglutide in patients with NASH is not known. METHODS We conducted a 72-week, double-blind phase 2 trial involving patients with biopsyconfirmed NASH and liver fibrosis of stage F1, F2, or F3. Patients were randomly assigned, in a 3:3:3:1:1:1 ratio, to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg or corresponding placebo. The primary end point was resolution of NASH with no worsening of fibrosis. The confirmatory secondary end point was an improvement of at least one fibrosis stage with no worsening of NASH. The analyses of these end points were performed only in patients with stage F2 or F3 fibrosis; other analyses were performed in all the patients. RESULTS In total, 320 patients (of whom 230 had stage F2 or F3 fibrosis) were randomly assigned 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). 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<0.001 for semaglutide 0.4 mg vs. placebo). An improvement in 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 = 0.48). The mean percent weight loss was 13% in the 0.4-mg group and 1% in the placebo group. 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%). Malignant neoplasms were reported in 3 patients who received semaglutide (1%) and in no patients who received placebo. Overall, neoplasms (benign, malignant, or unspecified) were reported in 15% of the patients in the semaglutide groups and in 8% in the placebo group; no pattern of occurrence in specific organs was observed. CONCLUSIONS 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 fibrosis stage.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available