Study summary · research use only
A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This 48-week phase 2 trial randomly assigned adults (human) with biopsy-confirmed MASH and fibrosis stage F1 through F3, in a 1:1:1:1 ratio, to once-weekly subcutaneous survodutide (2.4, 4.8, or 6.0 mg) or placebo, over a 24-week dose-escalation phase and 24-week maintenance phase. Among 293 participants, MASH improvement without worsening fibrosis occurred in 47%, 62%, and 43% of the three survodutide groups versus 14% with placebo. A decrease in liver fat content of at least 30% occurred in 63%, 67%, and 57% versus 14% with placebo; fibrosis improvement of at least one stage occurred in 34%, 36%, and 34% versus 22%. Nausea, diarrhea, and vomiting were reported more often with survodutide than placebo, while serious adverse events occurred in 8% versus 7%.
Abstract
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. 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. 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. 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.).
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