Fatty Liver Disease, MASLD
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New research from a Phase IIb pilot study has found that a weekly injection of semaglutide (Wegovy) reduced the amount of fat in the liver by 31% in people infected with HIV who have metabolic dysfunction-associated steatotic liver disease (MASLD). The regimen was also well tolerated noted the researchers who presented their findings Tuesday at the 2024 Conference on Retroviruses and Opportunistic Infections (CROI) in Denver.

Funding for the research—conducted in the U.S. and Brazil—is the first clinical trial of semaglutide for MASLD for people with HIV.

Previously called nonalcoholic fatty liver disease, MASLD causes an excess accumulation of fat in the liver which is caused by neither alcohol consumption nor viral hepatitis. The accumulation of fat, over time, can result in inflammation, tissue damage, as well as cardiovascular and liver disease. The most common liver disease in the U.S., MASLD is estimated to affect between 30% and 40% of those with HIV. Semaglutide is an approved medication for the treatment of type 2 diabetes and has received broad recognition as an effective drug for long-term weight loss and management.

In this study, patients with HIV and MASLD over the age of 18 whose viral load, or the amount of HIV in the blood, was suppressed to undetectable levels by antiretroviral therapy (ART). Study participants represented a wide range of ethnicities, ages, genders, and races. Of the 49 people included in the study analysis, 40 people (82%) were receiving ART treatment regimens which contained an integrase transfer inhibitor. These treatments are a class of antiretroviral therapies that have been shown to be effective suppressors of HIV, but have also been associated with weight gain among some of those who take them.

Enrolled patients self-administered a semaglutide injection each week and escalated doses until they reached a 1 mg dose on the fourth week. Patients were frequently monitored for drug safety.  At 24 weeks, using a specially designed MRI to measure the amount of fat in the liver, the team assessed each patient’s change in liver fat content. On average, the patients showed a 31% reduction of liver fat and 29% of the patients had a complete resolution of MASLD, defined by liver fat representing five percent or less of overall liver content. A separate analysis showed that while the volume of the psoas muscle, which connects the torso with the lower body, decreased there was no significant change in function.

The patients also demonstrated effects from the drug noted in previous studies of people without HIV, that included weight loss, reduced fasting blood glucose and reduced fasting triglycerides. Semaglutide was also generally well tolerated in a profile similar to previous studies in people without HIV. The most common side effects were gastrointestinal and two participants experienced more significant adverse events, but were still able to complete the study.

The findings suggest that semaglutide is a safe and effective therapy for those HIV patients who also suffer from MASLD, and could inform care regimens for healthier aging with HIV over a lifespan. Additional research is now being conducted to determine if people with HIV taking semaglutide experience any unique immunological or inflammatory pathway changes.

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