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 (marketed as Egrifta and Egrifta SV) is the only FDA-approved GHRH analog for therapeutic use in the United States. It was approved in 2010 specifically for the reduction of excess abdominal fat (lipodystrophy) in HIV-infected adults on antiretroviral therapy — a condition where metabolic disruption from both the virus and its treatment causes abnormal fat accumulation in the trunk region.
Tesamorelin is a modified form of GHRH(1-44) with a trans-3-hexenoic acid modification at the N-terminus that enhances receptor binding and extends duration of action compared to native GHRH. Unlike direct GH replacement, tesamorelin works through the body's own pituitary GH production, maintaining physiological feedback regulation.
Beyond its approved indication, tesamorelin has generated significant interest in anti-aging medicine and in the treatment of NAFLD/MASLD (metabolic dysfunction-associated steatotic liver disease). A 2019 study published in The Lancet HIV showed that tesamorelin reduced liver fat by 37% in HIV-infected patients with NAFLD — a finding that has implications well beyond the HIV population.
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 |
FDA-approved safety profile: As an FDA-approved drug, tesamorelin has well-characterized safety from clinical trials and post-marketing surveillance. The most common side effects are injection site reactions (redness, swelling, pain) occurring in approximately 10% of patients.
Arthralgia: Joint pain is reported in approximately 10-13% of patients and is likely related to increased GH/IGF-1 levels. The effect is typically mild and dose-dependent.
Peripheral edema: Fluid retention and swelling, consistent with GH elevation, occurs in a subset of patients.
Glucose effects: Tesamorelin may slightly impair glucose tolerance, consistent with GH's counter-regulatory effects on insulin. Glucose monitoring is recommended, particularly in patients with pre-diabetes or diabetes.
Hypersensitivity: Rare hypersensitivity reactions including rash, urticaria, and pruritus have been reported. Tesamorelin should be discontinued if hypersensitivity occurs.
Pregnancy: Tesamorelin is contraindicated in pregnancy due to potential effects on fetal development. It should be discontinued upon pregnancy confirmation.
| 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 |