Semaglutide Reduces Key Inflammation Markers in People Living with HIV Who Have Excess Abdominal Fat

What the researchers found

After 32 weeks of weekly subcutaneous semaglutide (1.0 mg), participants showed significant reductions in C-reactive protein (CRP), interleukin-6 (IL-6), and soluble CD163 (sCD163) compared to baseline — all markers strongly linked to cardiovascular risk and mortality in people with HIV. Soluble CD14 showed a trend toward reduction (P = .08). Importantly, monocyte proportions and T-cell phenotypes remained unchanged, suggesting the anti-inflammatory effect operates through pathways other than direct immune cell modulation.

Why it matters

Chronic inflammation is a major driver of cardiovascular disease and premature death in people with HIV, even when viral load is well-controlled. Finding treatments that can reduce this inflammation — beyond what antiretroviral therapy alone achieves — could meaningfully improve long-term outcomes. This trial provides randomized evidence that semaglutide has anti-inflammatory properties relevant to this high-risk population.

How the study worked

This was a single-site, randomized, double-blinded, placebo-controlled trial. Researchers enrolled 108 virologically suppressed, non-diabetic adults with HIV who had a BMI of 25 or higher and increased abdominal girth after starting antiretroviral therapy. Participants were split evenly into semaglutide and placebo groups for 32 weeks, with an 8-week dose titration period followed by 24 weeks at the full 1.0 mg weekly dose. Blood markers of inflammation and immune cell phenotypes were measured at baseline and after treatment.

What this study cannot tell us

The trial was conducted at a single site, which may limit generalizability. The 15% dropout rate in each group could introduce some bias. The study measured surrogate markers of inflammation rather than hard clinical endpoints like heart attacks or strokes. Monocyte and T-cell analyses showed no changes, leaving the precise anti-inflammatory mechanism unclear. The 32-week duration may not capture long-term effects.

How to read the evidence

This is a randomized, double-blinded, placebo-controlled trial — the gold standard for clinical evidence. The sample size of 108 is moderate, and the study measured validated biomarkers. However, it was single-site and used surrogate endpoints rather than clinical outcomes.

When this study was published

Published in 2025, this is a very recent study reflecting current clinical interest in the anti-inflammatory properties of GLP-1 receptor agonists.

The bigger picture

GLP-1 receptor agonists like semaglutide are generating enormous interest for benefits beyond blood sugar and weight control. This trial adds to a growing body of evidence that semaglutide has meaningful anti-inflammatory effects. For the HIV community specifically, where inflammation persists despite viral suppression and drives excess cardiovascular mortality, these findings open a promising new therapeutic avenue.

Questions still open

• Do the reductions in inflammatory markers translate into fewer cardiovascular events over the long term in people with HIV?
• What is the mechanism by which semaglutide reduces CRP, IL-6, and sCD163 without altering immune cell populations?
• Would longer treatment durations or different doses produce even greater anti-inflammatory benefits?

Common questions

Read the original research

The Effects of Semaglutide on Inflammation and Immune Activation in HIV-associated Lipohypertrophy.

Open forum infectious diseases, 12(4), ofaf152

Citation

Funderburg, Nicholas T; Ross Eckard, Allison; Wu, Qian; Sattar, Abdus; Ailstock, Kate; Cummings, Morgan; Labbato, Danielle; McComsey, Grace A. (2025). The Effects of Semaglutide on Inflammation and Immune Activation in HIV-associated Lipohypertrophy.. Open forum infectious diseases, 12(4), ofaf152. https://doi.org/10.1093/ofid/ofaf152