S tier · elite
The only compound in this group with an active FDA approval, supported by two adequately powered phase 3 randomised trials with a hard imaging endpoint and published long-term extension data.
tesamorelin
Tesamorelin is a synthetic 44-amino-acid analogue of human GHRH that binds pituitary GHRH receptors and increases endogenous, still-pulsatile GH secretion. It is approved in the United States to reduce excess abdominal visceral fat in adults with HIV-associated lipodystrophy, and the FDA label states that long-term cardiovascular safety has not been established.
the explanation
Tesamorelin is a lab-made copy of the natural brain hormone that tells the pituitary gland to release growth hormone. It is the only compound on this page that a regulator has actually approved, and only for one narrow use: shrinking deep belly fat in people with HIV-related fat redistribution.
regulatory status
FDA-approved prescription drug
Approved 2010 as Egrifta (later Egrifta SV and Egrifta WR, Theratechnologies) to reduce excess abdominal fat in HIV-infected adults with lipodystrophy; contraindicated in active malignancy, pituitary axis disruption and pregnancy.
how it works · proposed mechanism
Tesamorelin works one step upstream of growth hormone itself, at the pituitary GHRH receptor.
Binds the GHRH receptor
Tesamorelin is an agonist at the growth hormone-releasing factor receptor on anterior pituitary somatotrophs. Receptor occupancy triggers cAMP-dependent synthesis and release of stored growth hormone.
Keeps GH release pulsatile
Because the signal enters above the pituitary, negative feedback from IGF-1 and somatostatin remains intact. Published profiles show amplified physiological pulses rather than the flat elevation seen with exogenous recombinant GH.
Hexenoyl group resists degradation
The trans-3-hexenoyl cap on the N-terminal tyrosine blocks the DPP-4 cleavage that rapidly inactivates native GHRH. This is a stability modification, not a depot; the measured elimination half-life is still only 8-11 minutes.
Visceral fat is the target tissue
GH-driven lipolysis is disproportionately expressed in visceral adipose tissue, which is more lipolytically responsive than subcutaneous fat. Pooled phase 3 CT imaging showed a treatment effect of approximately -15% visceral adipose tissue versus placebo.
what’s reported
evidence shape
6 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
Glucose handling worsens: in the registration trials 5% of tesamorelin recipients versus 1% on placebo crossed HbA1c 6.5%, and the label describes an approximately 3.3-fold increased diabetes risk. The benefit is also entirely reversible, and the label states that long-term cardiovascular safety has never been established despite visceral fat being the surrogate that motivated the drug.
key published findings
- Human RCT (Falutz, NEJM 2007): 412 HIV-infected adults with abdominal lipodystrophy randomised 2:1 to tesamorelin 2 mg daily or placebo for 26 weeks; visceral adipose tissue fell significantly versus placebo with concurrent triglyceride reduction.
- Human RCT (Study 2, second phase 3 trial): 404 patients randomised, replicating the visceral fat endpoint; both trials together enrolled 816 patients with 543 exposed to active drug during the 26-week placebo-controlled phase.
- Human pooled analysis (Falutz, JCEM 2010, n=806): treatment effect of -15.4% visceral adipose tissue, mean IGF-1 +108 ± 112 vs -7 ± 64 ng/mL, triglycerides -37 mg/dL, with no clinically meaningful between-group differences in glucose parameters at weeks 26 and 52.
- Regulatory pharmacokinetics (FDA labels): mean elimination half-life 8 minutes after 1.4 mg EGRIFTA SV and 11 minutes after 1.28 mg EGRIFTA WR in healthy subjects, with median time to peak concentration 0.15 h.
- Safety signal (FDA label): elevated HbA1c ≥6.5% in 5% of tesamorelin-treated versus 1% of placebo-treated patients, with warnings for neoplasm risk requiring inactive pre-existing malignancy.
limitations of the evidence
- All pivotal efficacy data come from a single population, HIV-associated lipodystrophy, so extrapolation to metabolic visceral obesity without HIV rests on smaller and later studies.
- The primary endpoint is a CT imaging surrogate; no trial has been powered for cardiovascular events, mortality or diabetes incidence.
- Effects regress after discontinuation, and no trial has followed patients beyond the 52-week extension for oncological or cardiovascular outcomes.
identity
| full name | trans-3-hexenoyl-human growth hormone-releasing factor (1-44) amide |
| category | Growth Hormone |
| modality | peptide |
| formula | C221H366N72O67S |
| molar mass | 5135.86 g/mol |
| cas | 218949-48-5 |
| half-life | ~8-11 min (SC, healthy subjects; FDA label) |
| sequence | trans-3-hexenoyl-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg-Ala-Arg-Leu-NH2 |
laboratory handling
| storage | Lyophilised powder is stored refrigerated at 2-8°C per the approved product; research-grade lyophilised peptide is typically held desiccated at -20°C and protected from light. After reconstitution the FDA-labelled product is used immediately, and reconstituted peptide in laboratory settings is held at 2-8°C for short periods only. |
| solubility | Reconstituted in sterile water for injection in the approved presentation; in laboratory settings bacteriostatic or sterile water is the standard diluent, with dilute acetic acid used to aid dissolution of poorly soluble lots. |
| co-studied with | Because tesamorelin acts at the GHRH receptor and GHRPs act at GHS-R1a, the two classes are studied together on the rationale of complementary and partially synergistic GH release, but no published trial has tested tesamorelin in combination with a GHRP. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedU.S. Food and Drug Administration · 2019 · official
DailyMed / U.S. National Library of Medicine · 2024 · official
New England Journal of Medicine · 2007 · peer-reviewed
Journal of Clinical Endocrinology & Metabolism · 2010 · peer-reviewed
Clinical Infectious Diseases · 2012 · peer-reviewed
NIDDK / NCBI Bookshelf · 2020 · review
others in Growth Hormone