UTHealth Houston research: semaglutide reduces severity of fatty liver disease in people with HIV

Semaglutide is a safe, effective therapy for a common fatty liver disease in people with HIV, according to the results of a clinical trial presented by UTHealth Houston.

The use of semaglutide 1mg weekly was safe and effective in improving metabolic dysfunction-associated steatotic liver disease (MASLD) among people living with HIV, according to clinical trial findings presented by a UTHealth Houston researcher at the Conference on Retroviruses and Opportunistic Infections in Denver, Colorado, today.

Jordan E. Lake, MD, MSc, professor of infectious diseases with McGovern Medical School at UTHealth Houston and first author of the abstract, gave an oral presentation on the study, “Semaglutide Reduces Metabolic Dysfunction-Associated Steatotic Liver Disease in People with HIV: the SLIM LIVER Study.” The study evaluated semaglutide as a treatment for MASLD among people living with HIV without diabetes.

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. It mimics the GLP-1 hormone that is released in the gastrointestinal tract in response to eating. Recently, semaglutide has been associated with cardiometabolic improvements in the general population through its effects on weight reduction and systemic inflammation.

“What we found is that semaglutide is an extremely effective treatment for MASLD in people with HIV,” said Lake, who is also the SLIM LIVER protocol co-chair. “Along with reducing liver fat in people with HIV, participants also experienced weight loss and improvements in blood sugar, insulin resistance, and blood triglyceride levels.” 

MASLD encompasses the condition previously known as nonalcoholic fatty liver disease (NAFLD), an illness characterized by the accumulation of excess liver fat not caused by alcohol consumption or viral hepatitis. Over time, fat deposits cause local and systemic inflammation, as well as cellular damage, and can result in cardiovascular and progressive liver disease. According to previous research, an estimated 30-40% of people with HIV experience NAFLD, which is slightly higher than the average among people without HIV. MASLD is NAFLD in the presence of at least one traditional cardiovascular risk factor, such as high cholesterol or diabetes.

“Weight loss is the main treatment for fatty liver disease,” Lake said. “So, if you lose weight, you should lose liver fat, and that is certainly what we saw.”

In the Phase 2b, single-arm study, researchers found through an MRI technique, which was funded by McGovern Medical School and designed to measure the amount of fat in the liver, that a weekly 1 mg dose of semaglutide for 24 weeks was a safe and effective pharmacologic therapy for MASLD, showing evidence of broader cardiometabolic benefit. 

“Future analyses will assess if this drug has unique properties in people with HIV,” Lake said. “We’ve shown it does what we would expect it to do. Our future work is to show whether it also has unique benefits for our patients with HIV.”

The SLIM LIVER study, also called ACTG A5371, was sponsored by the ACTG, a global clinical trials network that conducts research to improve the management of HIV and other infections, with additional support from McGovern Medical School. The ACTG is sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634.

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