Phase 2 Data Show Early Liver Benefits With Zabopegdutide in MASH

Newly published 12-week phase 2 data suggest zabopegdutide (DD01) produced rapid improvements in liver fat, liver stiffness, and fibrosis biomarkers in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), with many benefits occurring before clinically meaningful weight loss.

The findings provide additional context for the company's recently announced positive 48-week phase 2 biopsy results, in which zabopegdutide achieved statistically significant improvements in both MASH resolution and fibrosis improvement among patients with biopsy-confirmed MASH and fibrosis stages F1-F3.

“Our recently announced 48-week biopsy results established that zabopegdutide produces clinically meaningful histological improvements in patients with MASH,” said Seulki Lee, PhD, President and CEO of D&D Pharmatech, in a statement. “The publication in the Lancet Gastroenterology & Hepatology demonstrates that these outcomes were foreshadowed by rapid and substantial improvements in liver health within the first 12 weeks of treatment. Importantly, many of these benefits occurred before meaningful weight loss, suggesting that zabopegdutide provides direct therapeutic effects on the liver beyond weight reduction. Together, these findings highlight the differentiated profile of zabopegdutide and support its potential to become a best-in-class therapy for MASH.”

Early Improvements in Liver Fat and Fibrosis Biomarkers

Zabopegdutide is an investigational once-weekly dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist designed to reduce hepatic steatosis while promoting weight loss and improving metabolic parameters. According to investigators, activation of the glucagon receptor is intended to enhance lipid mobilization from the liver, complementing the metabolic effects of GLP-1 receptor agonism.

The randomized, double-blind, placebo-controlled phase 2 DD01-DN-02 trial (NCT06410924) enrolled 67 adults who were overweight or obese with MASLD/MASH. The participants received a 2-week dose escalation to a maintenance dose of 40 mg once weekly or placebo.

At 12 weeks, 75.8% of patients receiving zabopegdutide achieved at least a 30% reduction in liver fat, while 72.7% experienced > 50% reductions. Additionally, 48.5% achieved normalization of liver fat, defined as less than 5% by MRI-proton density fat fraction (MRI-PDFF).

Investigators also reported significant reductions in liver stiffness measured by magnetic resonance elastography (MRE) as well as decreases in fibrosis biomarkers, including enhanced liver fibrosis (ELF) score and procollagen type III N-terminal peptide (PRO-C3). Improvements were also observed in liver enzymes, glycemic control, lipid parameters, and body weight, with mean weight reductions of 3.8% at week 12 and 6.4% at week 24.

Liver Benefits Observed Before Clinically Meaningful Weight Loss

A key finding from the analysis was the observation that improvements in liver health occurred even among participants who had not yet achieved clinically meaningful weight loss.

Among patients with less than 5% weight loss by week 12, treatment with zabopegdutide was associated with a 37.4% reduction in liver fat measured by MRI-PDFF and a 19.2% reduction in liver stiffness by MRE. Investigators noted patients who achieved at least 5% weight loss experienced even greater reductions in liver fat, suggesting both weight-dependent and potentially weight-independent effects may contribute to treatment response.

The investigators suggested these findings support the possibility that zabopegdutide exerts direct hepatic effects in addition to improvements associated with weight reduction. They further noted that the previously reported 48-week biopsy analysis demonstrated statistically significant improvements in MASH resolution and fibrosis among patients who experienced relatively modest weight loss, although additional studies are needed to further characterize the relationship between weight loss and histologic response.

Findings Provide Context for Positive 48-Week Biopsy Results

Although liver biopsy remains the reference standard for evaluating treatment response in MASH, noninvasive imaging and serum fibrosis biomarkers are increasingly used to monitor disease activity during clinical trials.

Investigators noted the current analysis suggests improvements in liver fat, liver stiffness, and fibrosis biomarkers may emerge within the first 12 weeks of treatment and precede the histologic improvements observed after 48 weeks. If confirmed in future studies, these findings could help inform earlier assessment of treatment response using noninvasive measures.

Zabopegdutide was generally well tolerated in the study and reached its target maintenance dose following a 2-week dose-escalation period.

References

1. D&D Pharmatech Announces The Lancet Gastroenterology & Hepatology Publication of Phase 2 Data Demonstrating Rapid, Weight-Independent Activity of Zabopegdutide (DD01) in MASLD/MASH. (2026, July 22). BusinessWire. https://www.businesswire.com/news/home/20260721648937/en/DD-Pharmatech-Announces-The-Lancet-Gastroenterology-Hepatology-Publication-of-Phase-2-Data-Demonstrating-Rapid-Weight-Independent-Activity-of-Zabopegdutide-DD01-in-MASLDMASH

2. D&D Pharmatech Announces Positive 48-Week Histology Results for Zabopegdutide (DD01), Demonstrating Statistically Significant Fibrosis Improvement and MASH Resolution. (2026, May 27). BusinessWire. https://www.businesswire.com/news/home/20260526295057/en/DD-Pharmatech-Announces-Positive-48-Week-Histology-Results-for-Zabopegdutide-DD01-Demonstrating-Statistically-Significant-Fibrosis-Improvement-and-MASH-Resolution