Zabopegdutide Improves Fibrosis, MASH Resolution at 48 Weeks

Zabopegdutide, an investigational liver-targeted dual glucagon-like peptide-1 (GLP-1)/glucagon receptor agonist, met both key histologic end points at 48 weeks in patients with metabolic dysfunction-associated steatohepatitis (MASH), according to phase 2 data presented by Mazen Noureddin, MD, MHSc, at The Liver Meeting 2026 in Denver, Colorado.

“Glucagon does have a direct effect on the liver, especially the anti-fibrotic effects,” Noureddin, professor of medicine at the Sherrie & Alan Conover Center for Liver Disease & Transplantation at Houston Methodist Hospital, told HCPLive.

How Did Zabopegdutide Perform at 48 Weeks?

In the double-blind DD01-DN-02 trial, 67 patients with MASLD or MASH were randomized to weekly subcutaneous zabopegdutide 40 mg or placebo.¹ Among patients with paired biopsies, 50.0% receiving zabopegdutide achieved at least 1-stage fibrosis improvement without worsening of MASH, compared with 15.8% receiving placebo (P = .03). MASH resolution without worsening of fibrosis occurred in 62.5% vs 5.3% (P < .001), and 37.5% vs 5.3% met both end points (P = .02).¹ An artificial intelligence-based measure of fibrosis also favored zabopegdutide.¹

The 48-week findings extend 12-week results published earlier this year, when 76% of treated patients achieved at least a 30% relative reduction in liver fat by MRI-proton density fat fraction, the trial’s primary end point, vs 12% receiving placebo.² Treatment-emergent adverse events were mostly gastrointestinal and mild or moderate, with 2 drug-related serious events reported.¹

Where Could Zabopegdutide Fit?

The data arrive as the MASH treatment landscape expands beyond resmetirom (Rezdiffra) and semaglutide (Wegovy), now approved for noncirrhotic MASH with moderate to advanced fibrosis.³ Noureddin notes that histologic benefit emerged despite a small biopsy subgroup, though phase 2b and 3 trials in larger populations are needed to confirm the results.

Watch the full interview to hear Noureddin discuss the rationale for the compound’s liver-targeted design, longer-term liver fat findings, and the agents in the MASH pipeline he is watching most closely.

References

1. Noureddin M, Dunn W, Patil R, et al. Topline histology data: zabopegdutide (DD01), a dual GLP-1/glucagon agonist, drives significant fibrosis improvement and MASH resolution at 48 weeks. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.
2. Noureddin M, Dunn W, Patil R, et al. The glucagon and GLP-1 receptor dual agonist DD01 for metabolic dysfunction-associated steatotic liver disease and steatohepatitis (DD01-DN-02): 12-week results from a randomised, double-blind, multicentre, placebo-controlled, phase 2 trial. Lancet Gastroenterol Hepatol. 2026;11(10):887-896. doi:10.1016/S2468-1253(26)00130-5
3. FDA approves semaglutide (Wegovy) injection 2.4 mg for noncirrhotic MASH. HCPLive. August 15, 2025. Accessed November 9, 2026. https://www.hcplive.com/view/fda-approves-semaglutide-wegovy-injection-2-4-mg-for-noncirrhotic-mash