GLP-1 for NASH? A Hepatologist's Perspective on Current Data

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In a recent interview, Kris Kowdley, MD, discusses current data surrounding use of GLP-1 receptor agonists in NAFLD and NASH as well as the prospective role of combination agents.

Nonalcoholic fatty liver disease (NAFLD) represents a significant treatment challenge for patients in the US and abroad. With a lack of FDA-approved therapies juxtaposed with an increased prevalence, driven in part by ballooning rates of type 2 diabetes, hepatologists and other care providers have been forced to manage the condition with available therapies.

Among those with type 2 diabetes, some clinicians purport anecdotal evidence in support of GLP-1 receptor agonist use as a means of achieving resolution of nonalcoholic steatohepatitis (NASH). In a phase 2 trial of patients with NASH published in the New England Journal of Medicine, use of semaglutide in doses of 0.1, 0.2, or 0.4 mg was associated with a significantly higher percentage of patients with NASH resolution than placebo, but was not associated with a significant between-group difference in the percentage of patients with an improvement in fibrosis stage.

However, the story for GLP-1 receptor agonists underwent a major shift in 2022 with the formal introduction of tirzepatide (Mounjaro), a novel dual GIP/GLP-1 receptor agonist from Eli Lilly and Company. Approved for treatment of type 2 diabetes in 2022, the agent grabbed more headlines for its effects in people with obesity or overweight at the American Diabetes Association (ADA) 2022 scientific sessions when SURMOUNT-1 data was presented. The company has disclosed plans to pursue an indication in chronic weight management, but also has an interest in exploring the agent as a treatment for NASH.

At the upcoming ADA 2023 Scientific Sessions in June, the community is expected to be given the opportunity to learn about another GLP-1 receptor agonist combination therapy: retatrutide. A novel GIP/GLP-1/Glucagon receptor triagonist, the agent is currently being examined as treatment for multiple conditions, including the phase 2 trial due to be presented at ADA 2023, which was conducted in patients with obesity, NAFLD, and type 2 diabetes.

For more on the topic, HCPLive sat down with Kris Kowdley, MD, a hepatologist and clinical faculty at the Elson S. Floyd College of Medicine, during a recent visit to the MJH Life Sciences studio to learn about his perspective on the potential role of GLP-1 receptor agonists and combination therapies as a treatment of NAFLD.