ACTG CROI Presentations Show That Semaglutide Improves Metabolic-Associated Steatotic Liver Disease Among People Living With HIV

Mar 08, 2024

LOS ANGELES, March 05, 2024 (GLOBE NEWSWIRE) — ACTG, a global clinical trials network focused on HIV and other infectious diseases, today announced an oral presentation from its SLIM LIVER study (also known as A5371), “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People with HIV: the SLIM LIVER Study” at the Conference on Retroviruses and Opportunistic Infections (CROI 2024) in Denver, Colorado. Yesterday, the SLIM LIVER poster “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER study” was presented. Together, these presentations demonstrate that semaglutide was highly effective in improving, and in some cases, resolving completely, metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as non-alcoholic fatty liver disease) among people living with HIV. They also demonstrate that while muscle volume decreased with semaglutide-induced weight loss, no significant changes in physical function were observed.

Today’s oral session was presented by SLIM LIVER Protocol Co-Chair Jordan E. Lake, M.D., M.Sc., UTHealth Houston and yesterday’s poster session was presented by Grace L. Ditzenberger, P.T., D.P.T., University of Colorado – Anschutz Medical Campus.

SLIM LIVER is the first study evaluating semaglutide as a treatment for MASLD among people living with HIV. MASLD is common among people living with HIV and likely acts synergistically with HIV to accelerate liver injury and organ dysfunction. Semaglutide is a glucagon-like peptide-1 receptor agonist that has been associated with cardiometabolic improvements in the general population through its effects on weight reduction and systemic inflammation.

“We are excited to present these important findings from SLIM LIVER at CROI this week,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California Los Angeles. “Participants in SLIM LIVER experienced weight loss and improvements in blood sugar, insulin resistance, and triglycerides, all of which are important improvements in cardiometabolic health. These findings have the potential to have a significant impact on the health and quality of life of people living with HIV.”

SLIM LIVER is a phase 2b single-arm, pilot study that enrolled adults living with HIV who were virally suppressed and had central adiposity (increased waist circumference), insulin resistance or pre-diabetes, and steatotic liver disease. All participants received semaglutide for 24 weeks (titrated to 1 mg, dosed subcutaneously every week, by week four).

In the primary analysis presented today, the median age of the 49 participants was 52 years old and their mean BMI was 35 kg/m2; 39 percent were Hispanic, 33 percent were Black/African American, 43 percent were women (cisgender and transgender), and 82 percent were taking antiretroviral therapy (ART) that included an integrase inhibitor. Participants experienced significant improvements in their weight, waist circumference, fasting glucose, BMI, hemoglobin A1C (a blood test that shows the glucose level over a period of three months), ALT (a liver enzyme that can become elevated when liver damage is present), and triglyceride concentrations. The primary analysis of SLIM LIVER demonstrated that semaglutide is a safe and effective pharmacologic therapy for MASLD among people living with HIV and has cardiometabolic benefits for this population.

The sub-analysis presented as a poster yesterday examined changes in muscle quality, quantity, and function among people living with HIV who were enrolled in SLIM LIVER. Among the 46 participants for whom muscle measurements were available, the mean age was 50 years old and their mean BMI was 35.5 kg/m2. This analysis found that among people living with HIV taking semaglutide in SLIM LIVER, muscle volume (quantity) decreased with weight loss, with no significant change in muscle fat (quality) or physical function.

Researchers found that the short-term side effect profile of semaglutide among people living with HIV was similar to that in people who do not have HIV.

“Even at the low dose of 1 milligram every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” said Dr. Lake. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”

SLIM LIVER is led by Dr. Lake, Kristine Erlandson, M.D., University of Colorado Anshchutz (Co-Chair), and Fred Sattler, M.D., University of Southern California (Vice-Chair). ACTG is led by Dr. Currier and Joseph J. Eron, M.D., University of North Carolina (ACTG Vice-Chair). It is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (which also funds ACTG) under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634, and received additional funding from UTHealth Houston McGovern School of Medicine.

About ACTG
ACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at 65 locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve.

Media Contact:
Rachel Reiss, ACTG