Tesamorelin, the GHRH analogue peptide: what it is, how it works, and what the studies measured
· Novatheris
Tesamorelin is a peptide that often gets confused with growth hormone. It is not. It is an analogue of the hormone that tells the pituitary to release growth hormone, and that difference changes everything that can be said about it.
This article gathers what published studies say about this peptide: its structure, how it acts, what the trials measured, and which questions are still open.
What tesamorelin is
Tesamorelin is a synthetic analogue of human GHRH. GHRH stands for growth hormone-releasing hormone: it is the signal the hypothalamus sends to the pituitary so it releases GH.
Tesamorelin does not replace GH. It stimulates the pituitary to release it in pulses, the way it does naturally. That GH, in turn, makes the liver produce more IGF-1, which is the marker almost every study measures to know whether the molecule is acting.
It exists as a commercial medicine (Egrifta, by Theratechnologies) for one very specific clinical use: reducing excess abdominal fat in adults with HIV and lipodystrophy. That medicine's label states it is not indicated for weight loss, because its effect on body weight is neutral.
The structure: a complete GHRH with one minimal change
What is interesting about tesamorelin, chemically, is how little it changes.
It carries the complete sequence of human GHRH, all 44 amino acids, ending in an amide. The only addition is a trans-3-hexenoyl group attached to the tyrosine at the starting end. Its chemical name sums it up: trans-3-hexenoyl-hGRF(1-44)-NH2.
That change makes it resistant to DPP-4, an enzyme that cuts and deactivates natural GHRH very quickly. That is why tesamorelin lasts longer than the original hormone.
Identity data for the notebook:
- Sequence: 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, with the hexenoyl group on the starting tyrosine.
- Formula: C221 H366 N72 O67 S, as free base. It comes as an acetate, with about 7 molecules of acetic acid.
- Molecular weight: 5135.9 Da.
- CAS: 218949-48-5.
A half-life of minutes
This is the figure that surprises people coming from the once-a-week metabolic peptides.
In healthy volunteers, the elimination half-life of subcutaneous tesamorelin is 8 minutes. Absolute bioavailability, meaning the share that reaches the blood, is below 4 %. And the area under the curve, a measure of how much drug circulates in total, is 34 % higher in HIV patients than in healthy volunteers.
In dogs, the measured half-life was 21 to 45 minutes.
Pharmacokinetics in healthy people and HIV patients are analyzed in González-Sales et al., Clin Pharmacokinet 2015. The preclinical evaluation of the molecule, back when it was called TH9507, is in Ferdinandi et al., Basic Clin Pharmacol Toxicol 2007.
Such a short half-life does not mean the effect lasts 8 minutes. What lasts is the signal on the pituitary and the IGF-1 rise that follows.
What the peptide's studies measured
Almost all the human evidence comes from HIV patients with abdominal fat accumulation, in placebo-controlled trials.
The first phase 3 trial. 412 people, 86 % men, over 26 weeks. Besides abdominal fat, it measured IGF-1: it rose 81.0 % with tesamorelin and fell 5.0 % with placebo. It is in Falutz et al., N Engl J Med 2007.
The second phase 3 trial. 404 people, a 6-month efficacy phase plus a 6-month extension. It is in Falutz et al., J Acquir Immune Defic Syndr 2010.
The pooled analysis. It combined both trials: 806 people, 543 on tesamorelin and 263 on placebo, up to 52 weeks. IGF-1 rose on average 108 ng/ml, versus a 7 ng/ml drop with placebo. The group that stayed on tesamorelin kept a -17.5 % reduction in visceral fat at 52 weeks. It is in Falutz et al., J Clin Endocrinol Metab 2010.
A trial outside HIV. In adults aged 55 to 87, healthy and with mild cognitive impairment, a 20-week trial set out to measure cognition. Along the way it recorded a 7.4 % drop in body fat and a 117 % rise in IGF-1. Its question was cognition, not fat or aging. It is in Baker et al., Arch Neurol 2012.
For a short overview of the molecule and its development, there is the note by Grunfeld et al. in Nat Rev Drug Discov 2011.
What is not known
High IGF-1 over a long time. The medicine's label states that the effects of prolonged IGF-1 elevation are unknown. In clinical use, IGF-1 is monitored throughout treatment.
The effect does not stay. The 52-week extension study found that once tesamorelin was stopped, visceral fat built back up. In the pooled analysis, the group switched to placebo at 26 weeks quickly lost the improvement. It is the work of Falutz et al., AIDS 2008.
Healthy populations. We located no published trial that tested tesamorelin for weight loss or as an anti-aging treatment in healthy people. The only controlled trial outside HIV that we cite had a different aim.
Tesamorelin as a research peptide
For anyone working with this peptide, two practical points.
The first is identity. With 44 amino acids and a group added at one end, the lab report has to confirm the correct molecular weight, not just high purity. At Novatheris every batch goes to Janoshik or Freedom Diagnostics, we require +99.5 % purity and we publish the report. The tesamorelin one is on its lab report page.
The second is storage. As a powder, or lyophilized (freeze-dried), it is stored at -20 °C, where it is stable. Reconstituted, 2 to 8 °C and only for the short term.
For research
The tesamorelin we sell is a research reagent, not a medicine. We do not give doses or directions for use.
The tesamorelin page has the full fact sheet with every citation, and the lab report shows the lab's results. Delivery in Costa Rica takes 2 hours in the GAM (the Greater Metropolitan Area around San José) and 24 hours in the rest of the country.