# Tesamorelin: Research Overview — Peptides For Doctors > A literature summary of Tesamorelin (TH9507), the FDA-approved GHRH analog for HIV-associated lipodystrophy: mechanism, RCT evidence, visceral fat and cognitive findings, and off-label considerations. A DPP-IV-resistant full-length GHRH(1-44) analog with FDA approval for HIV-associated lipodystrophy and the most rigorous RCT evidence of the three. ## 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. ![Tesamorelin — GHRH receptor activation and visceral-fat signaling in cold petrol tones](/images/tesamorelin.webp) ## 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](/sermorelin) has historical approval and decades of clinical use, tesamorelin has the most rigorous modern RCTs. Where [CJC-1295](/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](/compare) for the full side-by-side. --- A clinician-facing literature digest — what the research says, stated precisely, with citations and without advice.