Investigation of Efficacy and Safety of Three Dose Levels of Subcutaneous Semaglutide Once Daily Versus Placebo in Subjects With Non-alcoholic Steatohepatitis.

Summary

Investigation of efficacy and safety of three dose levels of subcutaneous semaglutide once daily versus placebo in subjects with non-alcoholic steatohepatitis

Timeline

Start

2016-11-30

Primary completion

2020-02-13

Completion

2020-03-19

Outcome

Met primary endpoint

paper NASH resolution was achieved with no worsening of fibrosis PMID 33185364 ↗

paper 59% in the 0.4-mg group, and 17% in the placebo group (P<0.001 for semaglutide 0.4 mg vs. placebo). PMID 33185364 ↗

Publications

• Results Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, Sanyal AJ, Sejling AS, Harrison SA; NN9931-4296 Investigators. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med. 2021 Mar 25;384(12):1113-1124. doi: 10.1056/NEJMoa2028395. Epub 2020 Nov 13.
• Nitze LM, Ratziu V, Sanyal AJ, Wong VW, Balendran C, Fleckner J, Skalshoi Kjaer M, Krarup N, Anstee QM. Exploration of Multiple Non-Invasive Tests for Assessing Response to Treatment in a Semaglutide Phase 2b Trial in Patients with MASH. Aliment Pharmacol Ther. 2026 Feb;63(3):396-404. doi: 10.1111/apt.70376. Epub 2025 Sep 23.
• Schattenberg JM, Gronbaek H, Kliers I, Ladelund S, Long MT, Nygard SB, Sanyal AJ, Davies MJ. Proteomic signatures reflect effects of semaglutide treatment for MASH. JHEP Rep. 2025 Jul 22;7(10):101521. doi: 10.1016/j.jhepr.2025.101521. eCollection 2025 Oct.
• Ratziu V, Francque S, Behling CA, Cejvanovic V, Cortez-Pinto H, Iyer JS, Krarup N, Le Q, Sejling AS, Tiniakos D, Harrison SA. Artificial intelligence scoring of liver biopsies in a phase II trial of semaglutide in nonalcoholic steatohepatitis. Hepatology. 2024 Jul 1;80(1):173-185. doi: 10.1097/HEP.0000000000000723. Epub 2023 Dec 19.
• Wai-Sun Wong V, Anstee QM, Nitze LM, Geerts A, George J, Nolasco V, Kjaer MS, Ladelund S, Newsome PN, Ratziu V. FibroScan-aspartate aminotransferase (FAST) score for monitoring histological improvement in non-alcoholic steatohepatitis activity during semaglutide treatment: post-hoc analysis of a randomised, double-blind, placebo-controlled, phase 2b trial. EClinicalMedicine. 2023 Nov 20;66:102310. doi: 10.1016/j.eclinm.2023.102310. eCollection 2023 Dec.
• Romero-Gomez M, Armstrong MJ, Funuyet-Salas J, Mangla KK, Ladelund S, Sejling AS, Shrestha I, Sanyal AJ. Improved health-related quality of life with semaglutide in people with non-alcoholic steatohepatitis: A randomised trial. Aliment Pharmacol Ther. 2023 Aug;58(4):395-403. doi: 10.1111/apt.17598. Epub 2023 Jun 16.
• Harrison SA, Calanna S, Cusi K, Linder M, Okanoue T, Ratziu V, Sanyal A, Sejling AS, Newsome PN. Semaglutide for the treatment of non-alcoholic steatohepatitis: Trial design and comparison of non-invasive biomarkers. Contemp Clin Trials. 2020 Oct;97:106174. doi: 10.1016/j.cct.2020.106174. Epub 2020 Oct 8.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Semaglutide	Peptide	0.1 mg	Subcutaneous
Subject	Semaglutide	Peptide	0.2 mg	Subcutaneous
Subject	Semaglutide	Peptide	0.4 mg	Subcutaneous

Indications