MASLD (metabolic dysfunction-associated liver disease), the new nomenclature for nonalcoholic fatty liver disease, a condition in which excessive fat builds up in the liver, is a common issue for people living with HIV (PLWH). Results of one study presented at CROI 2024 showed that a weekly injection of a low dose of semaglutide reduced liver fat for PLWH by an average of 30% with few adverse effects. Participants also had improvements in weight, waist circumference, fasting glucose, body mass index (BMI), ALT (a liver enzyme that can signal liver damage) and concentrations of triglycerides (a type of fat in the blood). Semaglutide is the active ingredient in Ozempic and Wegovy, which are used to manage diabetes and encourage weight loss.
Jordan E. Lake, MD, MSc, author of the study and a professor of infectious diseases at McGovern Medical School at UTHealth Houston, presented findings from a phase 2b open label pilot, called the SLIM LIVER study, the first study to evaluate semaglutide as a treatment for MASLD among PLWH. Among the 49 participants enrolled, all were virally suppressed on ART and had an elevated waist circumference as well as some measure of insulin resistance or pre-diabetes. The median age of enrollees was 52, with 37% cis women, 6% transgender women and 57% cis men. More than two-thirds were people of color.
Researchers measured changes in participants’ liver fat content using specialized MRI scans to measure intrahepatic content (content within the liver). If the MRI showed 5% of liver volume composed of intrahepatic triglycerides (IHTG), that participant was started on injections of semaglutide, beginning at .25 mg weekly, increasing to .5 mg at week two and boosted again to 1.0 mg from week four to the conclusion of the study at week 24.
Results showed overall significant reductions of IHTG at 24 weeks. More than half (58%) had a 31% relative reduction in IHTG and 28% had complete MASLD resolution at 24 weeks. “It was notable to us that greater IHTG reductions were observed in Hispanic and non-Hispanic White participants and people over 60 years” the research team reported.
Semaglutide induced weight loss across all populations in the study, and Dr. Lake noted that the mean weight loss was 17 lbs. (8 kg), with greater losses among women, non-Hispanic White participants and people over 40 years. “For those who lost weight under semaglutide there was an even greater reduction in liver fat,” Dr. Lake said.
She concluded saying low-dose (1 mg/weekly) semaglutide is an effective therapy for MASLD in PLWH over 24 weeks, and was well tolerated with very few adverse events. She noted a limitation of the study, that it didn’t track participants beyond 24 weeks. “There are some remaining questions about secondary benefits such as lean mass loss, the durability of benefits and strategies to maintain the benefits.”
Previous studies on semaglutide in the general population also saw improvements in blood sugar, insulin resistance and levels of blood triglycerides.
With MASLD, triglycerides and other fats can build up in the liver, disrupting its function. Although it is considered a “silent killer,” doing organ damage before significant symptoms appear, severe cases can progress to fibrosis (scarring of the liver) and liver cancer.
MASLD is a particular concern for PLWH, and likely acts with HIV to accelerate liver injury and organ dysfunction, according to the clinical trials network Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG). Other risk factors for PLWH include inflammation and oxidative stress from the virus and ART-related weight gain. Studies have estimated that about a third of PLWH have at least mild MASLD.
Semaglutide did not significantly change muscle fat
Weight loss can generally be accompanied by muscle loss, but not much is known about the effect of weight loss drugs on muscles. In a related session at CROI, Grace Ditzenberger, PT, DPT, a PhD student from the University of Colorado, presented a secondary analysis from SLIM LIVER, exploring effects of semaglutide on muscle structure and function for PLWH enrolled in the study.
Researchers examined the psoas muscle, which is used in walking and maintaining balance, through capturing liver magnetic resonance imaging proton-density fat fraction (MRI-PDFF) at baseline and at week 24. Researchers also analyzed participants’ ease of motion in rising from a chair and walking.
Analysis concluded that participants experienced a decrease in muscle volume (quantity) with weight loss, but no significant change in muscle fat (quality) or physical function, and that PLWH over age 60 years had the largest decline in muscle volume. Chair rise time and gait speed did not decline despite loss of psoas muscle volume, and the changes in function were not orrelated with change in overall weight or BMI, Dr. Ditzenberger said.
“More research is needed on long-term implications of semaglutide and on strategies to preserve muscle mass with weight loss interventions,” she concluded.
LARRY BUHL is a multimedia journalist based in Los Angeles. He has covered HIV/AIDS and other infectious diseases for more than two decades. In addition to POSITIVELY AWARE, he is a regular contributor to TheBody.com, Everyday Health and capitalandmain.com. His work has appeared in USA Today, Salon, Undark, KQED, The New York Times and others.