March 08, 2024
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Key takeaways:
- The first clinical trial of semaglutide for MASLD in people with HIV was a success.
- Weekly injections reduced the amount of fat in the liver by 31% in the small trial.
DENVER — A low weekly dose of semaglutide can safely minimize what used to be called nonalcoholic fatty liver disease in people with HIV, a first-of-its-kind study showed.
The condition, now known as metabolic dysfunction-associated steatotic liver disease (MASLD), occurs when excess fat accumulates in the liver unrelated to alcohol consumption or viral hepatitis.
Data derived from Lake JE, et al. Abstract 159. Presented at: Conference on Retroviruses and Opportunistic Infections; March 3-6, 2024; Denver.
MASLD is a leading cause of chronic liver disease in the United States and may be more common among people with HIV than the general population, according to Jordan E. Lake, MD, MSc, associate professor of infectious diseases at McGovern Medical School in Houston.
Patients with HIV also may develop “a more aggressive form” of MASLD that progresses to end-stage liver disease more rapidly, Lake said during a press conference at the Conference on Retroviruses and Opportunistic Infections.
Semaglutide, which is approved in the U.S. at low doses for treating type 2 diabetes and at high doses for weight loss, “has a lot of secondary effects, including reducing systemic inflammation through a number of pathways,” Lake said. “And while in most people with HIV traditional risk factors are driving their fatty liver disease, we do think there is a component of liver disease that is HIV specific, so some of those secondary effects of semaglutide may have unique benefits in people with HIV.”
Lake and colleagues enrolled 49 adults with MASLD and HIV into the open-label phase 2b SLIM LIVER study. The participants were all on suppressive ART, including 40 (82%) whose regimens included an integrase strand transfer inhibitor, a class of drugs that has been associated with weight gain.
Study participants injected themselves weekly with semaglutide, beginning with a dose of 0.25 mg and increasing to 1 mg at week 4, which is the dose prescribed for diabetes, Lake said.
The researchers monitored participants regularly for adverse events — “Nothing stood out as a safety signal,” Lake said — and performed MRIs on their livers after 24 weeks.
“What we saw were really great, clinically significant reductions of liver fat, even over that short period of time,” Lake said.
The absolute reduction in liver fat was a little over 4%, which corresponded to a more than 31% relative reduction, the researchers reported. Around one-third of participants had a complete resolution of MASLD, and almost 60% experienced at least a 30% reduction in liver fat, Lake said.
“In the hepatology world, the reason that number is important is because that’s … the number that’s associated with histologic improvements on biopsy,” Lake said.
According to Lake, participants also experienced an average weight loss of around 17 pounds in the 24 weeks, with significant improvements in glucose, insulin resistance and triglyceride levels.
Additional research is underway to understand whether people with HIV experience any unique immunologic or inflammatory pathway changes while taking semaglutide.
One thing that could limit its use in people with HIV is cost.
“Access is definitely an issue,” Lake said. “It’s a very expensive drug, among other things.”
References:
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Sources/Disclosures
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Source:
Lake JE, et al. Abstract 159. Presented at: Conference on Retroviruses and Opportunistic Infections; March 3-6, 2024; Denver.
Disclosures:
Lake reports receiving consulting or advisory fees from Theratechnologies and grants paid to his institution from Gilead Sciences.
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