Experimental Weight Loss Drug Shows Promise in Treating Liver Disease

A clinical trial investigating the experimental weight loss drug retatrutide suggests it may not only prevent the progression of liver disease but potentially reverse it. According to Dr. Arun Sanyal, a hepatologist at Virginia Commonwealth University and director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, more than 85% of obese participants with fatty liver disease in the trial reduced their liver fat to levels that no longer classified them as having the condition.

Dr. Sanyal presented these findings on November 13 at the American Association for the Study of Liver Diseases conference in Boston. The study is part of a larger phase 2 clinical trial sponsored by Eli Lilly and Co., which was published in the New England Journal of Medicine in June. A phase 3 trial commenced in August.

The findings indicate that retatrutide could serve as a “bottom-up” therapy for high-risk patients. “The implications of this trial are profound,” said Dr. Sanyal. “We could eliminate liver fat early in the disease course, potentially reducing long-term risks like cardiac, metabolic, renal, and liver-related complications from obesity. This research offers hope for tackling a disease that currently lacks approved therapies.”

Dr. Sanyal’s study evaluated the effects of two doses of retatrutide on fatty liver disease, now termed metabolic dysfunction-associated steatotic liver disease (MASLD). Patients with MASLD exhibit liver fat comprising 5% or more of the liver’s weight and at least one cardiometabolic risk factor, such as diabetes, heart disease, or stroke.

By week 48 of the trial, 93% of participants taking the higher dose of retatrutide reduced their liver fat below 5%. “This is a dramatic outcome,” Dr. Sanyal noted. “In obese populations, up to 75% have excess liver fat. Retatrutide could become a transformative treatment for early-stage liver disease.”

Retatrutide works by activating the GIP, GLP-1, and glucagon receptors, which regulate hunger, satiety, and blood sugar levels, leading to weight loss.

Obesity remains a critical public health issue, contributing to conditions such as type 2 diabetes, cardiovascular disease, and liver disease. Approximately 33 million Americans have type 2 diabetes, with 5–7% of them developing clinically significant liver disease. The interplay between type 2 diabetes and liver disease is increasingly recognized, as each condition heightens the risk of the other. Up to 70% of people with type 2 diabetes also have excess liver fat.

The trial enrolled 98 obese adults aged 18–75, who were randomly assigned retatrutide doses. By week 48, participants taking 8mg of retatrutide experienced an 81.7% relative reduction in liver fat, while those on 12mg achieved an 86% reduction. Liver fat decreased to below 5% in 89% of the 8mg group and 93% of the 12mg group. Average weight loss over the 48 weeks was 23.8% for the 8mg group and 25.9% for the 12mg group.

The U.S. Food and Drug Administration recently approved Eli Lilly’s Zepbound for treating obesity in adults. The drug, also marketed as Mounjaro for type 2 diabetes, has shown similar benefits in improving liver health by reducing liver fat.