One of these three peptides is an FDA-approved drug. One was approved and then pulled from the market, for business reasons rather than safety. One never made it through its trials. Yet sermorelin, tesamorelin and ipamorelin are still sold and discussed as a set of "growth hormone peptides," as if they were three strengths of one thing. In fact, two of them copy one natural signal, and the third copies a different one.
The short answer
Sermorelin and tesamorelin press the same button. Ipamorelin presses a different one. Sermorelin and tesamorelin are both versions of GHRH, the brain's main signal to release growth hormone. Sermorelin is a shortened copy. Tesamorelin is the full-length copy with a chemical cap that makes it last longer. Ipamorelin acts on a separate receptor, the ghrelin receptor, which is a second route to the same outcome. Tesamorelin is an FDA-approved drug for one narrow use. Sermorelin was approved and then withdrawn for commercial reasons. Ipamorelin never completed development.
How growth hormone release is controlled
Growth hormone is made in the pituitary gland, at the base of the brain. Its release is set by a push and a brake.
- The push comes from GHRH (growth hormone-releasing hormone), sent down from the hypothalamus.
- A second push comes through the ghrelin receptor, also called GHS-R1a. Ghrelin is best known as a hunger hormone, but it also prompts growth hormone release.
- The brake is somatostatin, which holds release back.
Because the system runs on pushes and brakes, growth hormone is released in pulses rather than as a steady stream. Peptides that work through these natural receptors leave that pulsing pattern and its feedback controls in place, which is one reason researchers study them rather than growth hormone itself.
Side by side
| Sermorelin | Tesamorelin | Ipamorelin | |
|---|---|---|---|
| What it copies | GHRH, first 29 of 44 amino acids | GHRH, all 44 amino acids | Ghrelin's action (not its structure) |
| Receptor | GHRH receptor | GHRH receptor | Ghrelin receptor (GHS-R1a) |
| Size | 29 amino acids | 44 amino acids plus a chemical cap | 5 amino acids |
| Stability trick | None; lasts minutes | A cap on the front end blocks the enzyme that cuts GHRH | Unnatural building blocks resist enzymes |
| Regulatory history | Approved in the 1990s for growth hormone deficiency in children; withdrawn from the US market in 2008 for commercial reasons, not safety | FDA-approved in 2010 (Egrifta) for one narrow use | Reached mid-stage trials; missed its main goal; never approved |
| Evidence tier | C | A (for its approved use) | D |
Sermorelin in more detail
Natural GHRH is 44 amino acids long. In the early 1980s, researchers found that the first 29 carry its full activity at the receptor. Sermorelin is that 29-amino-acid piece.
It was approved in the 1990s, under the name Geref, to test for and treat growth hormone deficiency in children. It was withdrawn from the US market in 2008. The withdrawal was a business decision by its maker, not a response to a safety problem, and that distinction is worth keeping. Its weakness is its lifespan. It is broken down within about 10 to 20 minutes, which is the problem the next two molecules were designed around.
Tesamorelin in more detail
Tesamorelin keeps all 44 amino acids of GHRH and adds one small change: a trans-3-hexenoyl group attached to the front end. That cap blocks DPP-4, the enzyme that normally clips GHRH at its second position and switches it off. The rest of the molecule behaves like natural GHRH.
In 2010 the FDA approved tesamorelin, under the name Egrifta, for one specific use: reducing excess abdominal fat in adults with HIV-associated lipodystrophy, a condition in which fat is redistributed around the organs. That approval rests on controlled clinical trials, which puts tesamorelin at tier A for that indication. It is the only peptide in this group with a current FDA label, and the approval applies only to that condition.
Ipamorelin in more detail
Ipamorelin is a five-amino-acid peptide from the late 1990s. It includes an unusual amino acid called Aib and two mirror-image (D-form) amino acids, which make it hard for enzymes to break down.
It belongs to a family of ghrelin-receptor compounds called GHRPs, which includes GHRP-2 and GHRP-6. What set ipamorelin apart in the research was selectivity. Earlier compounds in the family also raised cortisol and prolactin, two other hormones, and GHRP-6 caused marked hunger. In animal studies, ipamorelin released growth hormone with little effect on cortisol or prolactin.
Ipamorelin was later tested in people for a different purpose entirely: speeding the return of normal bowel function after surgery, a ghrelin-related effect. That mid-stage trial did not meet its main goal, and development stopped. A negative result is still a result, and it is part of the record.
A note on CJC-1295 and "DAC"
CJC-1295 is often mentioned alongside these three. It is a modified version of sermorelin's 29 amino acids, with four substitutions that make it more resistant to enzymes. The version without DAC is sometimes called Mod GRF 1-29.
DAC stands for Drug Affinity Complex. It is a chemical attachment that lets the peptide bind to albumin, the most common protein in the blood. Bound to albumin, the peptide is protected from breakdown and removal. In early human studies, that stretched its half-life from minutes to roughly a week. "With DAC" and "without DAC" are therefore not two strengths of one compound. They behave very differently over time.
Why they are grouped together, and why that is misleading
All of these compounds end at the same place, growth hormone release, so they are often sold and discussed as a set. The differences matter more than the shared endpoint.
- Different receptors. Sermorelin and tesamorelin act on the GHRH receptor. Ipamorelin acts on the ghrelin receptor.
- Different chemistry. Each takes a different approach to the same problem: natural signals that last only minutes.
- Different evidence. One current approval, one withdrawn approval, and one development program that ended with a missed endpoint.
The takeaway
Sermorelin, tesamorelin and ipamorelin are three answers to one question: how to prompt growth hormone release through the body's own controls. Sermorelin is the short original. Tesamorelin is the full-length, capped version, and the only one approved today, for one narrow use. Ipamorelin takes the separate ghrelin-receptor route and is notable for its selectivity. Its clinical story ended with a missed endpoint.
Frequently asked questions
What is the difference between sermorelin and tesamorelin?
Both are versions of GHRH, the brain's main signal for growth hormone release. Sermorelin is the first 29 amino acids of GHRH and is broken down within minutes. Tesamorelin is the full 44 amino acids with a chemical cap that protects it from the enzyme that normally inactivates GHRH.
What is the difference between sermorelin and ipamorelin?
They act on different receptors. Sermorelin acts on the GHRH receptor. Ipamorelin is a five-amino-acid peptide that acts on the ghrelin receptor, a separate route to growth hormone release.
Is tesamorelin FDA approved?
Yes. Tesamorelin was approved by the FDA in 2010, under the name Egrifta, for reducing excess abdominal fat in adults with HIV-associated lipodystrophy. The approval applies only to that condition.
Why was sermorelin discontinued?
Sermorelin, sold as Geref, was withdrawn from the US market in 2008 for commercial reasons. The withdrawal was not due to a safety finding.
Is ipamorelin FDA approved?
No. Ipamorelin reached mid-stage clinical trials for bowel recovery after surgery, did not meet its main goal, and was not developed further.
What does DAC mean in CJC-1295?
DAC stands for Drug Affinity Complex, a chemical attachment that lets the peptide bind to albumin in the blood. This greatly extends how long it lasts. CJC-1295 without DAC, also called Mod GRF 1-29, lasts minutes rather than days.