Tesamorelin is a synthetic analog of human growth hormone-releasing hormone (GHRH) conjugated with trans-3-hexenoic acid at the N-terminus to enhance stability and bioavailability. It was FDA-approved in 2010 (as Egrifta) for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy. It is the only GHRH analog with regulatory approval specifically for visceral adipose tissue reduction.

Tesamorelin binds to GHRH receptors on pituitary somatotrophs, stimulating the synthesis and pulsatile release of endogenous growth hormone. The trans-3-hexenoic acid modification protects the N-terminus from enzymatic degradation by dipeptidyl peptidase IV (DPP-IV), extending its biological activity. The resulting GH elevation promotes lipolysis (particularly in visceral fat), increases IGF-1, and may improve hepatic fat metabolism. It preserves the hypothalamic-pituitary feedback axis.

• Reduced visceral adipose tissue by 15-18% in HIV-associated lipodystrophy trials (Falutz et al., 2007)
• Decreased liver fat and improved NAFLD-related biomarkers in clinical studies
• Maintained or improved trunk fat distribution without worsening glucose tolerance
• Improved cognitive function parameters in aging adults in the TERI-MCI trial (Baker et al., 2019)
• Did not worsen glucose homeostasis despite increasing GH and IGF-1 levels

1. Tesamorelin for HIV-associated abdominal fat accumulation
   N Engl J Med, 2007
2. Effects of tesamorelin on non-alcoholic fatty liver disease
   Lancet HIV, 2019
3. Tesamorelin and cognitive outcomes in older adults
   J Clin Endocrinol Metab, 2019

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