Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia

    Research output: Contribution to journalLetterpeer-review

  3. Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Monoclonal Antibody for Patients with Covid-19. Reply

    Research output: Contribution to journalLetterpeer-review

  5. A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Repeated Activation of Noradrenergic Receptors in the Ventromedial Hypothalamus Suppresses the Response to Hypoglycemia

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Effects of carbamazepine, eslicarbazepine, valproic acid and levetiracetam on bone microarchitecture in rats

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Semaglutide for the treatment of non-alcoholic steatohepatitis: Trial design and comparison of non-invasive biomarkers

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Detection of Hypoglycemia Using Measures of EEG Complexity in Type 1 Diabetes Patients

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Philip N Newsome
  • Kristine Buchholtz
  • Kenneth Cusi
  • Martin Linder
  • Takeshi Okanoue
  • Vlad Ratziu
  • Arun J Sanyal
  • Anne-Sophie Sejling
  • Stephen A Harrison
  • NN9931-4296 Investigators
View graph of relations

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.).

Original languageEnglish
JournalThe New England journal of medicine
Volume384
Issue number12
Pages (from-to)1113-1124
Number of pages12
ISSN0028-4793
DOIs
Publication statusPublished - 25 Mar 2021
Externally publishedYes

ID: 61735551