Zabopegdutide Produces Rapid Liver-Fat Reduction in MASLD/MASH—but GI Toxicity Is Frequent: The Lancet Gastroenterology & Hepatology | October 2026

What Did the Study Find?

This 12-centre US trial randomised 67 adults with overweight or obesity and MASLD/MASH to once-weekly zabopegdutide—DD01, a dual GLP-1/glucagon-receptor agonist—or placebo. Seventy-eight per cent had biopsy-confirmed MASH.

At week 12, 76% (25/33) receiving DD01 achieved at least a 30% relative reduction in MRI-PDFF liver fat, compared with 12% (4/34) receiving placebo (adjusted RR 6.3, 95% CI 2.5–15.9; P<0.0001). The absolute difference was 64 percentage points. However, treatment-emergent adverse events occurred in 85% versus 68%: nausea affected 55% versus 18%, vomiting 30% versus 12%, and diarrhoea 27% versus 18%. Treatment was discontinued because of adverse events in 12% versus 3%; two serious events—abdominal pain and acute cholecystitis—occurred with DD01.

Why Does It Matter?

The liver-fat effect is large and rapid, but MRI-PDFF is a surrogate. This small, short analysis does not establish histological MASH resolution, fibrosis improvement or clinical benefit.

GastroAGI Takeaway: Zabopegdutide is a compelling phase 2 signal, not a practice-changing therapy yet—biopsy-based durability and longer-term safety must drive interpretation.