In a small 6‑month trial, the peptide tesamorelin helped people with HIV and belly fat lose a few centimeters around the waist, but it didn’t show a clear improvement in brain function compared to standard care. The study was short, had few participants, and lacked a placebo, so the cognitive benefit remains uncertain.

In people with HIV who are virally suppressed with antiretroviral therapy, abdominal obesity (AO) is linked to neurocognitive impairment (NCI), potentially due to visceral adiposity, inflammation, and reduced insulin-like growth factor 1 (IGF-1). Tesamorelin, a growth hormone-releasing hormone, reduces AO and increases IGF-1, suggesting that it might mitigate NCI in people with HIV and viral suppression. This 6-month phase 2 randomized open-label clinical trial compared tesamorelin vs standard of care (SOC) for NCI in people with HIV who were virally suppressed and abdominally obese (elevated waist circumference [WC]). Exclusions included conditions other than HIV causing NCI, active substance use disorder, and malignancy. Seventy-three participants were randomized 3:2 to tesamorelin or SOC (2 mg subcutaneously daily). The primary outcome was the change in neurocognitive performance at 6 months, with secondary outcomes including WC, mood, and daily functioning. The groups were well matched at baseline. The tesamorelin group showed a trend toward improved neurocognitive performance after 6 months (mean change, 0.146; 95% CI, -.002 to .294; P = .060) while the SOC group did not (0.103; 95% CI, -.095 to .301; P = .295), but the between-group difference was not significant (P = .673). IGF-1 levels increased, but changes did not correlate with summary regression change score or WC. The tesamorelin group had a greater reduction in WC than the SOC group (median difference, -2.7 cm; P = .015). While tesamorelin reduced WC, the cognitive benefits did not significantly differ between groups. Recognizing the limitations of insufficient power and no placebo arm, this study suggests no clear benefit of short-term AO reduction with tesamorelin on NCI.