Novo drugs cut fibrosis markers in alcohol-related liver disease

Three Novo Nordisk drugs developed for obesity and fatty liver disease each lowered a blood-based liver fibrosis score compared with placebo in heavy drinkers with alcohol-related liver disease, according to Phase 2 results presented on November 8, 2026 at The Liver Meeting 2026, the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Denver.

Vijay Shah, MD, of the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester, Minnesota, presented the trial as abstract 0087 in an 11:00 a.m. Mountain time slot. The trial title and Novo’s abstract use the term “alcohol-related liver disease”; AASLD’s session title uses “alcohol-associated liver disease.” Both refer to the same condition, and this story uses the trial’s wording.

The trial

The multinational, placebo-controlled study randomized 270 people with heavy alcohol use and advanced liver disease, HCPLive reported. ClinicalTrials.gov lists the Novo Nordisk-sponsored study as NCT06409130, completed, with an actual enrollment of 270.

Participants received 28 weeks of a once-weekly injection of one of three drugs or one of two combinations:

• Zalfermin, coded NNC0194-0499 in the trial registry, an analog of the hormone FGF21
• Cagrilintide, an amylin analog
• Semaglutide, the GLP-1 receptor agonist also sold as Wegovy
• Zalfermin plus semaglutide
• Cagrilintide plus semaglutide, the pairing Novo calls CagriSema

The registry splits the study into two groups, each with its own matched placebo: one testing zalfermin and semaglutide, and one testing cagrilintide and CagriSema. A published first-in-human study identifies zalfermin as the drug “formerly NNC0194-0499.”

What was reported

The primary endpoint was the change in the Enhanced Liver Fibrosis (ELF) score, a blood test that estimates scarring, from week 0 to week 28. HCPLive reported that every active treatment arm met it, lowering ELF scores compared with placebo. Liver stiffness and PRO-C3, a blood marker tied to collagen formation, also improved consistently.

The investigators describe the study as the first randomized trial to show that drug treatment can improve fibrosis biomarkers in this disease, according to HCPLive.

Drinking fell in every group, including placebo, but the drug arms did not differ significantly from placebo. HCPLive says that pattern suggests the benefit may come in part from direct effects on the liver. Shah also pointed to metabolic risk factors in many participants, consistent with what clinicians call MetALD, as a possible contributor.

“If you took a liver of somebody who had MASLD or MASH and somebody who had alcohol, they looked the same,” Shah told HCPLive, explaining why drugs studied in fatty liver disease were tested here.

No drug is approved to target fibrosis in alcohol-related liver disease, and sustained abstinence remains the cornerstone of care, HCPLive noted. Zalfermin and cagrilintide are investigational, and none of the three drugs is approved for this use.

What is not known

• Effect sizes. No ELF changes, differences from placebo, liver stiffness values or p-values have been published in the public sources. It is not known which arm did best, or whether the combinations beat single drugs.
• Safety. Shah discussed safety and tolerability in a video interview, but no detailed adverse event data are public in the written sources.
• Durability and outcomes. ELF, liver stiffness and PRO-C3 are surrogate markers. A 28-week trial cannot show whether the drugs prevent cirrhosis, liver failure or death.
• Next steps. We found no Novo Nordisk press release on these results, and Novo has not said publicly whether it will run a larger trial.

This story summarizes a conference presentation and trial records. It is not medical advice.