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

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.

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.

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.

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.

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.