Abstract
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 biopsy-confirmed 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. (Funded by Novo Nordisk;
ClinicalTrials.gov number, NCT02970942. opens in new tab.)
Original language | English |
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Pages (from-to) | 113-1124 |
Number of pages | 12 |
Journal | New England Journal of Medicine |
Volume | 384 |
Issue number | 12 |
Early online date | 13 Nov 2020 |
DOIs | |
Publication status | Published - 25 Mar 2021 |
Keywords
- Semaglutide
- Nonalcoholic steatohepatitis
- NASH
- Placebo-controlled trial
ASJC Scopus subject areas
- Medicine(all)