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SHR Neuro Cancer Cardio Lipid Metab Microb
Sanyal, AJ; Bedossa, P; Fraessdorf, M; Neff, GW; Lawitz, E; Bugianesi, E; Anstee, QM; Hussain, SA; Newsome, PN; Ratziu, V; Hosseini-Tabatabaei, A; Schattenberg, JM; Noureddin, M; Alkhouri, N; Younes, R, , 1404-0043, Trial, Investigators.
A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis.
N Engl J Med. 2024; 391(4):311-319
Doi: 10.1056/NEJMoa2401755
PubMed
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- Study Group Members Med Uni Graz:
- Stauber Rudolf
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- Abstract:
- BACKGROUND: Dual agonism of glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor may be more effective than GLP-1 receptor agonism alone for treating metabolic dysfunction-associated steatohepatitis (MASH). The efficacy and safety of survodutide (a dual agonist of glucagon receptor and GLP-1 receptor) in persons with MASH and liver fibrosis are unclear. METHODS: In this 48-week, phase 2 trial, we randomly assigned adults with biopsy-confirmed MASH and fibrosis stage F1 through F3 in a 1:1:1:1 ratio to receive once-weekly subcutaneous injections of survodutide at a dose of 2.4, 4.8, or 6.0 mg or placebo. The trial had two phases: a 24-week rapid-dose-escalation phase, followed by a 24-week maintenance phase. The primary end point was histologic improvement (reduction) in MASH with no worsening of fibrosis. Secondary end points included a decrease in liver fat content by at least 30% and biopsy-assessed improvement (reduction) in fibrosis by at least one stage. RESULTS: A total of 293 randomly assigned participants received at least one dose of survodutide or placebo. Improvement in MASH with no worsening of fibrosis occurred in 47% of the participants in the survodutide 2.4-mg group, 62% of those in the 4.8-mg group, and 43% of those in the 6.0-mg group, as compared with 14% of those in the placebo group (P<0.001 for the quadratic dose-response curve as best-fitting model). A decrease in liver fat content by at least 30% occurred in 63% of the participants in the survodutide 2.4-mg group, 67% of those in the 4.8-mg group, 57% of those in the 6.0-mg group, and 14% of those in the placebo group; improvement in fibrosis by at least one stage occurred in 34%, 36%, 34%, and 22%, respectively. Adverse events that were more frequent with survodutide than with placebo included nausea (66% vs. 23%), diarrhea (49% vs. 23%), and vomiting (41% vs. 4%); serious adverse events occurred in 8% with survodutide and 7% with placebo. CONCLUSIONS: Survodutide was superior to placebo with respect to improvement in MASH without worsening of fibrosis, warranting further investigation in phase 3 trials. (Funded by Boehringer Ingelheim; 1404-0043 ClinicalTrials.gov number, NCT04771273; EudraCT number, 2020-002723-11.).
- Find related publications in this database (using NLM MeSH Indexing)
- Adult - administration & dosage
- Aged - administration & dosage
- Female - administration & dosage
- Humans - administration & dosage
- Male - administration & dosage
- Middle Aged - administration & dosage
- Dose-Response Relationship, Drug - administration & dosage
- Double-Blind Method - administration & dosage
- Fatty Liver - drug therapy, pathology
- Injections, Subcutaneous - adverse effects
- Liver - pathology, drug effects
- Liver Cirrhosis - drug therapy, pathology
- Receptors, Glucagon - agonists
- Glucagon-Like Peptide-1 Receptor Agonists - administration & dosage