Weekly Semaglutide Injections Reduced Dangerous Belly Fat in People Living with HIV

What the researchers found

Semaglutide produced a statistically significant reduction in abdominal visceral adipose tissue of 30.82 cm² (95% CI: -50.13 to -11.51), representing a 30.6% decrease compared to placebo over 32 weeks. Abdominal subcutaneous fat also decreased by 42.01 cm² (11.2% reduction), and total body fat dropped by 18.9%.

These reductions occurred without a statistically significant increase in treatment-related adverse events, though one grade 4 elevated lipase event and two cases of cholelithiasis were observed in the semaglutide group.

Why it matters

HIV-associated lipohypertrophy has lacked effective treatments despite increasing cardiometabolic risk. This trial provides the first randomized controlled evidence that a GLP-1 receptor agonist peptide can meaningfully reduce visceral fat in this population, potentially opening a new therapeutic avenue for a condition that affects many people living with HIV on long-term antiretroviral therapy.

How the study worked

This was a randomized, double-blind, placebo-controlled phase 2b trial conducted at a single US site. 108 adults with HIV, controlled viral load, BMI of 25 or more, and lipohypertrophy (but no diabetes) were randomly assigned 1:1 to receive either semaglutide (titrated over 8 weeks to 1.0 mg weekly for 24 weeks) or placebo by subcutaneous injection. Fat was measured by body compartment at 32 weeks. Analysis followed intention-to-treat principles.

What this study cannot tell us

This was a single-center trial with a relatively small sample size of 108 participants. All participants were from one US site, limiting generalizability. The study excluded people with diabetes, so results may not apply to HIV patients with concurrent diabetes. The 32-week duration may not capture long-term effects or sustained benefit after stopping treatment. A few serious adverse events (elevated lipase, gallstones) need further evaluation in larger populations.

How to read the evidence

This is a randomized, double-blind, placebo-controlled phase 2b trial published in The Lancet Diabetes & Endocrinology, providing strong evidence. However, the single-center design and moderate sample size (n=108) place it below a large multicenter phase 3 trial.

When this study was published

Published in 2024, this is a very recent study reflecting current clinical practice and the latest understanding of GLP-1 agonists in HIV care.

The bigger picture

GLP-1 receptor agonists like semaglutide have transformed obesity and diabetes treatment, but their role in HIV-specific metabolic complications was previously unexplored in rigorous trials. This study bridges that gap, suggesting that peptide-based therapies may address the unique fat distribution abnormalities seen in HIV, which traditional weight-loss approaches have struggled to correct.

Questions still open

• Do the fat-reducing benefits of semaglutide persist after the medication is stopped in people with HIV?
• How does semaglutide perform in HIV patients who also have type 2 diabetes, given they were excluded from this trial?
• What is the long-term safety profile of GLP-1 agonists specifically in people on antiretroviral therapy?

Common questions

Read the original research

Once-weekly semaglutide in people with HIV-associated lipohypertrophy: a randomised, double-blind, placebo-controlled phase 2b single-centre clinical trial.

The lancet. Diabetes & endocrinology, 12(8), 523-534

Citation

Eckard, Allison Ross; Wu, Qian; Sattar, Abdus; Ansari-Gilani, Kianoush; Labbato, Danielle; Foster, Theresa; Fletcher, Aaron A; Adekunle, Ruth O; McComsey, Grace A. (2024). Once-weekly semaglutide in people with HIV-associated lipohypertrophy: a randomised, double-blind, placebo-controlled phase 2b single-centre clinical trial.. The lancet. Diabetes & endocrinology, 12(8), 523-534. https://doi.org/10.1016/S2213-8587(24)00150-5