Tesamorelin

Tesamorelin (Egrifta) is a synthetic analogue of human growth hormone-releasing hormone that stimulates the synthesis and release of endogenous growth hormone. ^[1] It is the first and, so far, only treatment indicated for the reduction of excess abdominal fat in patients with HIV-associated lipodystrophy, having been approved by the Food and Drug Administration in November 2010. ^{[1] [2]}

As a growth hormone-releasing hormone analogue, tesamorelin restores normal GH pulsatility and amplitude, and selectively reduces visceral fat, intima media thickness and triglycerides. ^[3] Subcutaneous tesamorelin is effective in reducing visceral adipose tissue but does not affect subcutaneous adipose tissue to a clinically significant extent, and discontinuation of therapy results in reaccumulation of visceral adipose tissue. ^[1]

In two 26-week, well designed clinical trials in patients with HIV-associated central fat accumulation, tesamorelin significantly reduced visceral adipose tissue and improved other body composition measures such as trunk fat and waist circumference. ^{[1] [2]} A meta-analysis of five randomized controlled trials found that tesamorelin was associated with a significant reduction in visceral adipose tissue (mean difference -27.71 cm2), a reduction in hepatic fat percentage (mean difference -4.28%), and an increase in lean body mass (mean difference 1.42 kg). ^[4] Tesamorelin improves body composition, hepatic fat, lean body mass, and IGF-1 levels in HIV-associated lipodystrophy without serious side effects or perturbation of glucose, and has shown promise for MASLD in people with HIV. ^{[4] [5]} Beyond its approved indication, tesamorelin has been noted to improve cognitive function in older persons, but such uses are not FDA-approved and supporting evidence is limited. ^[3]

Tesamorelin is generally well tolerated, with treatment-emergent serious adverse events occurring in fewer than 4% of patients during 26 weeks of therapy, most being injection-site reactions or events known to be associated with growth hormone therapy such as arthralgia, headache and peripheral oedema. ^[1] Potential limitations for its use include high cost and a lack of long-term safety and adherence data. ^[2]