The tesamorelin ipamorelin blend
The tesamorelin ipamorelin blend pairs two peptides that act on two different receptors of the same pituitary cell. Tesamorelin presses the GHRH receptor, ipamorelin the ghrelin receptor. The reason anyone combines the two classes goes back to 1990, when 18 men given GHRH(1-44) together with GHRP-6 released more GH than with either alone [11].
That 1990 result is the whole evidence base for the pair. No study has given tesamorelin with ipamorelin, so there is no human data and no safety record for the blend. What does exist is a large trial record for tesamorelin alone and a small one for ipamorelin alone, set out below, and the same gap for its better-known cousin, CJC-1295 ipamorelin.
Same target, same years
In the mid-2000s two Montreal companies were chasing the same clinical prize with two versions of the same hormone. Theratechnologies had tesamorelin, the full 44-residue GHRH with a protective hexenoyl group on its N-terminus. ConjuChem had CJC-1295, the 1-29 fragment with four substitutions and an albumin-binding tail. Both aimed at the same clinical indication.
ConjuChem's phase 2 trial, 120 planned participants over 12 weeks, started in December 2005 and was terminated in September 2006 without posting results [6]. Theratechnologies' programme produced a NEJM paper in 2007 and an FDA approval on 10 November 2010 [3]. Neither tesamorelin nor CJC-1295 is authorised in the European Union.
What tesamorelin's trials established
Falutz and colleagues randomised 412 participants, 86 % of them men, to tesamorelin or placebo for 26 weeks, in a phase 3 trial published in the New England Journal of Medicine in 2007. The trial met its primary endpoint, measured by CT, and IGF-1 rose 81.0 % against a 5.0 % fall on placebo (P < 0.001) [1]. That trial is the core of the file the FDA reviewed before its 2010 approval.
Seven years later, Stanley and colleagues at Massachusetts General Hospital ran a second randomised, placebo-controlled trial: fifty participants over 6 months, 48 of whom received the study drug, published in JAMA in 2014 [2]. Two controlled trials, a published primary endpoint and a regulatory review: that is the depth of record CJC-1295 and ipamorelin never reached.
What CJC-1295 was shown to do
CJC-1295's human record is two trials in healthy adults, both published in 2006. After a single administration, mean GH rose 2 to 10-fold for 6 days or more and IGF-1 1.5 to 3-fold for 9 to 11 days. The half-life was 5.8 to 8.1 days [4].
In a second study, one week after a single administration, trough GH was 7.5-fold higher, mean GH 46 % higher and IGF-1 45 % higher, with the pulses unchanged [5]. Those are hormone measurements, not clinical outcomes. No CJC-1295 trial measured a clinical endpoint, because the trial that would have did not finish. The form used in research blends is the one without the albumin linker, explained in CJC-1295 DAC vs no DAC.
GH secretion was increased after CJC-1295 administration with preserved pulsatility. The frequency and magnitude of GH secretory pulses were unaltered.
Where ipamorelin fits
Ipamorelin is a five-residue agonist of the ghrelin receptor, designed at Novo Nordisk to release GH without raising cortisol or prolactin [7]. In healthy men it has a 2-hour half-life [8]. Its clinical development was two phase 2 trials in a post-operative setting. The first, in 114 analysed participants, missed its primary endpoint [9], and the second, with 320 participants, posted no results [10].
Clinics that offer "tesamorelin ipamorelin" apply the two-receptor logic to the approved GHRH analogue instead of the unapproved one. No trial has tested either pairing, and tesamorelin's approval covers tesamorelin alone, in one indication. All three peptides are prohibited in sport under WADA class S2 [12].
What the comparison means
No study compared tesamorelin with CJC-1295, so the literature does not say which releases more GH. CJC-1295's week-long half-life is a feature tesamorelin lacks. The difference is in the evidence. One molecule was carried through the trials that turn a mechanism into a measured outcome, and the other was not. A clinical figure quoted for "CJC-1295 ipamorelin", if a page quotes one, belongs to tesamorelin.
Reading the tesamorelin trials is the best available way to see what a GHRH analogue can do in people. Reading the CJC-1295 trials is the only way to see what CJC-1295 did. The older GHRH analogue is compared in sermorelin vs CJC-1295 ipamorelin.
