Tesamorelin: The Approved GHRH Analog

The short version

Tesamorelin is a synthetic analog of the full 44-amino-acid human GHRH sequence, with one modification: a trans-3-hexenoic acid group added to the N-terminus. That modification blocks the enzyme (DPP-IV) that would otherwise rapidly degrade the peptide, extending plasma stability while preserving full GHRH receptor activity. Like sermorelin, it stimulates the pituitary to release the body's own growth hormone — it does not supply exogenous GH ^[1].

Tesamorelin is the only peptide on this desk with current FDA approval. That approval (NDA 022505, 2010) is specifically for reducing excess abdominal fat in HIV-positive adults on antiretroviral therapy who have developed lipodystrophy. Every other use — general visceral-fat reduction, anti-aging, cognition, NAFLD in non-HIV patients — is off-label and investigational ^[9]. A 2026 meta-analysis of five RCTs confirms significant visceral fat reduction in the approved indication ^[8]. This page summarizes the evidence; it provides no dose recommendations.

What it is

Tesamorelin is GHRH(1-44)-NH2 with a trans-3-hexenoyl (trans-3-hexenoic acid) group conjugated to the N-terminal tyrosine. The molecular formula of the free base is C221H366N72O67S. It is supplied clinically as the acetate salt. The N-terminal modification confers resistance to cleavage by dipeptidyl peptidase-IV (DPP-IV), extending its plasma half-life substantially compared to unmodified GHRH while preserving the full 44-residue receptor-binding sequence.

Tesamorelin was developed by Theratechnologies under the research code TH9507. It received FDA approval in November 2010 under the trade name Egrifta for HIV-associated lipodystrophy and later as Egrifta SV and Egrifta WR for formulation variants. All trade names refer to the same active molecule.

How it works

Tesamorelin binds the GHRH receptor on anterior-pituitary somatotrophs, activating the Gs/adenylyl cyclase/cAMP/PKA signaling cascade that stimulates both synthesis and pulsatile secretion of endogenous GH. The resulting GH drives hepatic production of IGF-1, which in turn promotes lipolysis — the breakdown of fat stores — preferentially in visceral (intra-abdominal) adipose tissue ^[1].

Because tesamorelin amplifies the pituitary's own pulsatile rhythm rather than supplying a constant exogenous GH signal, its metabolic profile differs from recombinant GH. In healthy men, 2 mg/day for 2 weeks increased mean overnight GH by 0.5 ug/L (P=0.004) and raised IGF-1 by 181 ug/L (P<0.0001), while neither fasting glucose nor insulin-stimulated glucose uptake was significantly affected — suggesting preserved insulin sensitivity at this duration ^[11].

What the research shows

Approved indication: HIV-associated lipodystrophy (RCT evidence). A 2026 meta-analysis pooling five randomized controlled trials in HIV-associated lipodystrophy found tesamorelin reduced visceral adipose tissue by a mean of 27.71 cm2 (95% CI -38.37 to -17.06; P<0.001), reduced trunk fat by 1.18 kg, reduced hepatic fat fraction by 4.28%, and increased lean body mass by 1.42 kg, all without serious adverse events ^[8].

Visceral fat and liver fat (JAMA RCT). In a 6-month JAMA trial of 50 HIV-positive adults, tesamorelin 2 mg/day produced a visceral fat treatment effect of -42 cm2 (P=0.005) and a net hepatic lipid reduction of -2.9% (P=0.003) ^[10].

52-week durability. In a larger program (tesamorelin n=273, placebo n=137), VAT reduction was sustained at -18% versus baseline over 52 weeks (P<0.001); visceral fat reaccumulated upon discontinuation, and glucose changes over 52 weeks were not clinically significant ^[12].

Cognition (aging trial). A 2012 RCT in 152 older adults (66 with mild cognitive impairment) found 20 weeks of daily subcutaneous GHRH analog produced a favorable effect on cognition (P=0.03), increased IGF-1 by 117% within the physiologic range, and reduced body fat by 7.4% ^[2]. Adverse events were mild. Note that a 2025 HIV cognition trial did not show significant neurocognitive improvement over standard care, so cognitive findings are mixed.

Liver safety. The NIH LiverTox monograph assigns tesamorelin a likelihood score of E — unlikely cause of clinically apparent liver injury — noting no reported attributable liver-injury cases and no de novo serum-enzyme elevations in trials ^[9].

Reported effects, cautions and safety

The cautions below are drawn from the cited literature.

• Approval is narrow. FDA approval applies specifically to HIV-positive adults with antiretroviral-related lipodystrophy. Use in non-HIV populations, for general visceral-fat reduction, anti-aging, or other indications is off-label with no approved human indication ^[9].
• Visceral fat reaccumulates on discontinuation. Benefits are contingent on continued dosing; fat returns within weeks of stopping treatment ^[12].
• IGF-1 elevation and oncologic consideration. Active malignancy is a labeled contraindication. While trials showed no excess malignancy signal over 52 weeks, long-term oncologic-safety data in non-HIV populations are limited ^[1].
• Glucose monitoring. Modest glucose perturbation can occur; monitoring is warranted in individuals with prediabetes or dysglycemia, though the dedicated diabetes trial found no significant HbA1c change ^[12].
• WADA prohibition. Tesamorelin is prohibited in sport under WADA Prohibited List category S2 (peptide hormones, growth factors, related substances and mimetics), in- and out-of-competition.
• Research-grade material. Research-grade tesamorelin sold for laboratory use lacks the purity, potency, and sterility oversight of the FDA-approved product.

Where it fits in GH-axis research

Tesamorelin occupies a distinct position among the three: it is the only one with a current, active FDA approval, and it has the largest randomized trial evidence base of the class ^[8]. Where sermorelin has historical approval and decades of clinical use, tesamorelin has the most rigorous modern RCTs. Where CJC-1295 extends half-life for convenience, tesamorelin's DPP-IV resistance achieves metabolic stability without the multi-day sustained elevation. Its ceiling, however, is a narrow approved indication — making it the clearest illustration on this desk of how a well-evidenced peptide can still have most of its use categorized as off-label. See the comparison page for the full side-by-side.