A 44-amino-acid modified GHRH analog with a trans-3-hexenoic acid group attached to the N-terminal tyrosine. The only GHRH-based drug currently FDA-approved for therapeutic use in the US — specifically for reducing excess visceral abdominal fat in HIV-infected patients with lipodystrophy.
Tesamorelin is a synthetic 44-amino-acid analog of human GHRH with a single modification: a trans-3-hexenoic acid group conjugated to the N-terminal tyrosine residue. This modification improves stability and bioavailability compared to native GHRH.
It is marketed as Egrifta and is FDA-approved specifically for reducing excess visceral abdominal fat (lipodystrophy) in HIV-infected patients on antiretroviral therapy. It is the only GHRH-based drug currently approved for therapeutic use in the United States.
Tesamorelin activates the GHRH receptor on pituitary somatotrophs, stimulating GH production through the Gs-cAMP-PKA signaling cascade. The resulting GH increase preferentially mobilizes visceral fat through activation of hormone-sensitive lipase in visceral adipocytes, which have higher GH receptor density than subcutaneous fat.
| Pathway | Effect | Significance |
|---|---|---|
| GHRH-R activation | Full agonist at pituitary GHRH receptor | Stimulates endogenous GH production preserving pulsatility |
| Visceral fat reduction | GH-mediated lipolysis in visceral adipose | 17% reduction in trunk fat in Phase III trials |
| IGF-1 increase | GH-driven hepatic IGF-1 production | Increases IGF-1 within normal physiological range |
| Liver fat reduction | Reduces hepatic steatosis | Potential benefit for NAFLD/NASH (being studied) |
| No glucose worsening | Unlike direct GH, minimal impact on insulin sensitivity at approved dose | Safer metabolic profile for diabetic patients |
| Study | Design | Findings | Level |
|---|---|---|---|
| Phase III (HIV lipodystrophy) | RCT, n=816 | 17% reduction in visceral adipose tissue at 26 weeks vs placebo. FDA approval basis. | Level I |
| NAFLD/NASH | Phase II, n=61 | Reduced hepatic fat fraction by 37% in HIV patients with fatty liver | Level II |
| Cognitive function | Clinical study | Improved cognitive function in HIV patients, possibly via IGF-1 effects on hippocampus | Level II-III |
| Long-term safety | Extension studies, 2+ years | Sustained fat reduction; no significant safety concerns. IGF-1 remained in normal range. | Level I-II |
Injection site reactions: Erythema, pruritus, and pain at injection site are the most common side effects (~25%).
Arthralgia: Joint pain reported in ~13% of patients. Related to GH/IGF-1 increase.
Fluid retention: Peripheral edema and carpal tunnel symptoms can occur.
Theoretical cancer risk: GH/IGF-1 elevation could theoretically promote tumor growth. FDA label warns about this. Monitor for malignancy.
| Jurisdiction | Status |
|---|---|
| FDA | Approved: Egrifta (tesamorelin) for HIV lipodystrophy (2010). Daily SC injection. |
| Off-label | Increasingly used off-label for general visceral fat reduction and anti-aging |
| WADA | Banned under S2 |