Survodutide Linked to Major Fatty Liver Disease Improvement

On MONDAY, June 17, 2024, findings were released indicating that most patients taking survodutide, a dual agonist targeting both the glucagon receptor and the glucagon-like peptide-1 (GLP-1) receptor, experience significant improvements in metabolic dysfunction-associated steatohepatitis (MASH) without a worsening of fibrosis. These results come from a phase 2 study published online on June 7 in the New England Journal of Medicine, coinciding with the annual congress of the European Association for the Study of the Liver, held from June 5 to 8 in Milan.

The study, led by Dr. Arun J. Sanyal from Virginia Commonwealth University in Richmond, evaluated the efficacy and safety of survodutide among individuals with confirmed MASH and liver fibrosis. The research included 293 adults with biopsy-confirmed MASH and fibrosis stages F1 through F3. Participants were randomly assigned in a 1:1:1:1 ratio to receive either a weekly subcutaneous injection of survodutide at doses of 2.4 mg, 4.8 mg, or 6.0 mg, or a placebo, for a duration of 48 weeks.

The results showed significant improvements in MASH without worsening fibrosis among 47 percent, 62 percent, and 43 percent of participants in the 2.4-mg, 4.8-mg, and 6.0-mg survodutide groups, respectively. This was in stark contrast to the placebo group, where only 14 percent experienced similar improvements. Furthermore, a reduction in liver fat content by 30 percent or more was observed in 63 percent, 67 percent, and 57 percent of participants in the respective survodutide groups, compared to just 14 percent in the placebo group. Improvement in fibrosis by at least one stage occurred in 34 percent, 36 percent, and 34 percent of the survodutide groups, respectively, versus 22 percent in the placebo group.

However, the study also noted a higher frequency of adverse events among those taking survodutide. Nausea was reported by 66 percent of participants on survodutide, compared to 23 percent in the placebo group. Similarly, diarrhea was reported by 49 percent of the survodutide group compared to 23 percent in the placebo group, and vomiting was reported by 41 percent versus 4 percent in the placebo group. Serious adverse events were recorded in 8 percent of those taking survodutide, slightly higher than the 7 percent noted in the placebo group.

Dr. Sanyal highlighted the significance of these findings, stating, "These data demonstrate that direct liver targeting with glucagon agonism in addition to GLP-1 effects helps resolve nonalcoholic fatty liver disease and improve fibrosis while maintaining the benefits of GLP-1 agonism."

The study was funded by Boehringer Ingelheim, the company that manufactures survodutide.