Tesamorelin Reduced Belly Fat in People with HIV but Didn't Clearly Improve Cognitive Function | Research

The takeaway

Tesamorelin significantly reduced abdominal obesity in people with HIV but failed to produce a significant cognitive benefit over standard care in this 6-month trial.

-2.7 cm waist circumference
Median reduction with tesamorelin versus standard of care over 6 months (p=0.015)

What the researchers found

In a 6-month trial of 73 people with HIV and abdominal obesity, tesamorelin (2 mg daily subcutaneous) significantly reduced waist circumference compared to standard of care (median difference -2.7 cm, p=0.015). However, while the tesamorelin group showed a trend toward improved cognitive performance (mean change 0.146, p=0.060), the between-group difference in cognition was not statistically significant (p=0.673). IGF-1 levels increased with tesamorelin but did not correlate with cognitive changes or waist circumference reduction.

Why it matters

Cognitive impairment affects up to half of people with HIV even when the virus is well controlled, and abdominal obesity may contribute through inflammation and hormonal changes. This trial tested whether reducing belly fat with a GHRH peptide could also improve brain function — a novel approach to HIV-associated cognitive problems. The negative cognitive result is important because it suggests that simply reducing visceral fat may not be enough to reverse established cognitive deficits.

The numbers in context

n=73 · 3:2 randomization · 2 mg tesamorelin daily SC · 6 months · WC reduction -2.7 cm (p=0.015) · Cognitive trend p=0.060 · Between-group cognitive p=0.673

How the study worked

Phase 2 randomized open-label clinical trial. 73 virally suppressed adults with HIV and abdominal obesity randomized 3:2 to tesamorelin (2 mg subcutaneous daily) or standard of care for 6 months. Primary outcome was change in neurocognitive performance. Secondary outcomes included waist circumference, mood, and daily functioning. Excluded patients with non-HIV causes of cognitive impairment, active substance use, or malignancy.

Who was studied

Virally suppressed adults with HIV and abdominal obesity (elevated waist circumference)

What this study cannot tell us

Open-label design (no placebo) introduces potential bias. Underpowered — the study itself acknowledges insufficient statistical power. Six months may be too short for meaningful cognitive recovery. The lack of a placebo arm makes it difficult to separate treatment effects from natural variation. IGF-1 increases did not correlate with cognitive changes, questioning the proposed mechanism.

How to read the evidence

Moderate evidence: randomized clinical trial published in a major infectious disease journal, but limited by open-label design, small sample size with acknowledged insufficient power, and no placebo arm.

When this study was published

Published in 2025. Highly current and directly relevant to ongoing debates about tesamorelin's potential neurological benefits in HIV populations.

The bigger picture

Tesamorelin is the only FDA-approved treatment for HIV-associated lipodystrophy, and there's been growing interest in whether its metabolic benefits extend to the brain. This trial represents the first randomized attempt to test that hypothesis directly. While the cognitive results were negative, the study was underpowered, and the trend toward improvement (p=0.060) leaves the door open. It also highlights the broader challenge of treating HIV-associated cognitive impairment, where no effective pharmacological therapy currently exists.

Questions still open

Would a larger, longer, placebo-controlled trial with tesamorelin reveal a significant cognitive benefit?
If visceral fat reduction alone doesn't improve cognition, is inflammation rather than adiposity the key driver of HIV-associated cognitive impairment?
Could combining tesamorelin with other neuroprotective interventions produce synergistic cognitive benefits?

Common questions

What is tesamorelin and what is it approved for?

Tesamorelin is a synthetic peptide that stimulates the pituitary gland to release growth hormone. It's FDA-approved under the brand name Egrifta to reduce excess abdominal fat in people with HIV who develop lipodystrophy — a redistribution of body fat that can occur with antiretroviral therapy.

Why might reducing belly fat help cognitive function in HIV?

Visceral abdominal fat produces inflammatory molecules and hormonal changes (like reduced IGF-1) that may contribute to brain inflammation and cognitive decline. The theory was that reducing this fat with tesamorelin might lower inflammation and increase IGF-1, potentially improving brain function — but this trial did not confirm that hypothesis.

Read the original research

Effects of Tesamorelin on Neurocognitive Impairment in Persons With HIV and Abdominal Obesity.

The Journal of infectious diseases, 231(5), 1230-1238

View on PubMed ↗Publisher’s paper ↗

Citation

Ellis, Ronald J; Vaida, Florin; Hu, Keren; Dube, Michael; Henry, Brook; Chow, Felicia; Heaton, Robert K; Lee, Daniel; Sattler, Fred. (2025). Effects of Tesamorelin on Neurocognitive Impairment in Persons With HIV and Abdominal Obesity.. The Journal of infectious diseases, 231(5), 1230-1238. https://doi.org/10.1093/infdis/jiaf012