A medication used to treat diabetes and obesity – and touted on social media for weight loss – can be a powerful weapon against a type of fatty liver disease in people with HIV.
This is according to a study – “The Effect of Open-Label Semaglutide on Metabolic Dysfunction–Associated Steatotic Liver Disease in PeopleWith HIV” by Jordan E. Lake, Douglas W. Kitch, Amy Kantor, Kristine Erlandson, et al – that appeared in the Annals of Internal Medicine.
In this study, the researchers focused on the use of a medication called semaglutide in treating metabolic dysfunction-associated steatotic liver disease, or MASLD, among people living with HIV.
MASLD is the most common cause of chronic liver disease and of liver-related deaths. It’s a new term for what used to be called nonalcoholic fatty liver disease, which as the name suggests is not linked to drinking alcohol. It’s associated with at least one metabolic risk factor, such as obesity or high cholesterol.
“It basically just means increased fat in the liver,” Erlandson said. “Fatty liver is one of the more common reasons for a liver transplant… We know that fatty liver occurs in about 25% to 30% of the general population, but it occurs in up to 50% of people with HIV.”
In some cases, fatty liver in people with HIV can be related to the side effects of certain antiretroviral therapies, particularly older ones, she says. It appears that HIV may help to accelerate MASLD’s progression to liver damage, cirrhosis, and liver failure.
Best known as Ozempic, Wegovy
“Currently the mainstay of treatment for fatty liver is weight loss, and we all know that weight loss can be difficult for many people to achieve and to ultimately maintain,” Erlandson said.
This led the researchers to focus on investigating semaglutide as a therapy.
Semaglutide was approved by the US Food & Drug Administration in 2017 as a treatment for type 2 diabetes, often under the brand name Ozempic. More recently, a higher dosage of semaglutide, sold as Wegovy, was approved for use for treating obesity or for managing weight with accompanying health conditions.
Lately, the drug has gained widespread popularity as an off-label treatment for general weight loss, boosted by internet chatter and celebrity endorsements.
“Because weight loss is the recommendation for fatty liver, and there aren’t any approved therapies for decreasing liver fat, our idea was that if we had an effective drug for weight loss, we would likely see improvements in fatty liver,” Erlandson said.
Fatty liver also is associated with metabolic dysfunction involving regulation of glucose, she added. “If we could target that metabolic aspect, too, we might have greater improvement. There also appear to be anti-inflammatory and immune changes associated with this class of drugs. Since this may contribute to progression of fatty liver in people with HIV, we thought that the immune and inflammation pathways may be a unique aspect of how this drug may work in people with HIV and fatty liver, making it more effective than just giving a different weight-loss drug.”
A highly effective therapy
For the trial, adult participants with HIV and MASLD were recruited in the US and Brazil. Participants also had a larger-than-typical waist circumference, but they were not necessarily overweight. It was an “open label, single arm” study, meaning that there was no control group getting a placebo, and participants knew what drug they were getting.
After 24 weeks, the participants were evaluated: 29% showed no signs of MASLD, and another 58% showed significant reductions in liver fat, enough to lower their risk of progression to advanced liver disease. “And we saw improvements in many other metabolic markers,” Erlandson said. “Not surprisingly, we saw very impressive weight loss among essentially all of our participants.”
The study concluded that semaglutide is “a highly effective MASLD therapy” for people with HIV. It also found evidence that the drug may reduce risk of cardiovascular disease, which is higher among people with HIV, by reducing liver fat.
Erlandson noted that study participants were given a smaller dose of semaglutide than the FDA now allows. “I suspect if we’re using the larger doses now approved, we’ll see an even greater benefit,” she says.
Meanwhile, she said that insurance companies should be be convinced to treat fatty liver as a qualifying condition for semaglutide, “because many patients can’t afford to pay for it out of their pocket and insurance often won’t cover it.”
