Evidence review
Growth-Hormone Secretagogues: What the Evidence Actually Shows
These compounds reliably raise IGF-1. That is the surrogate. When trials measured function, fracture recovery or disease progression, the results changed.
Three different things wear one name
A growth-hormone secretagogue is anything that makes the pituitary release more growth hormone. Three chemically unrelated groups get filed under it.
GHRH analogs copy growth-hormone-releasing hormone. Tesamorelin and sermorelin sit here. Tesamorelin's label describes it as GHRH(1-44)1.
Ghrelin-receptor agonists copy ghrelin, the hunger hormone, which also triggers growth-hormone release. Ipamorelin is a peptide in this group.
Non-peptide mimics do the same job without being peptides at all. MK-677, also called ibutamoren, is an orally active nonpeptide mimic of a growth-hormone-releasing peptide2. It gets marketed inside "peptide" conversations and it is not one — see what a peptide is.
The surrogate moves, reliably
This is the class's defining feature and its trap. The compounds discussed here raise IGF-1, consistently and measurably, in trials with hundreds of participants.
In a 12-month trial of 563 patients with mild to moderate Alzheimer's disease, MK-677 25 mg daily raised serum IGF-1 by 60.1% at six weeks and 72.9% at twelve months3.
In a six-month trial of 161 patients recovering from hip fracture, MK-0677 raised serum IGF-1 by 84% against 17% on placebo4.
Target engagement is not in question. What happened next is.
What happened when the outcome was measured
Alzheimer's progression. In that 563-patient trial, across the CIBIC-plus, ADAS-Cog, ADCS-ADL and CDR-sob, the authors reported no significant differences between treatment groups over 12 months. Their stated conclusion: despite evidence of target engagement indicated by the IGF-1 rise, MK-677 was ineffective at slowing progression3.
Hip-fracture recovery. In the 161-patient trial, there were no significant differences between MK-0677 and placebo in improvement on functional performance measures or on the overall Sickness Impact Profile score. Three of four lower-extremity measures favoured the drug numerically and none reached statistical significance4.
Post-operative ileus. A phase 2 trial of the ghrelin-receptor agonist ipamorelin (NCT00672074) enrolled 117 patients undergoing bowel resection. Median time to first tolerated meal was 25.3 hours on ipamorelin against 32.6 hours on placebo, p = 0.15. The authors reported no significant differences on the key or secondary efficacy analyses5.
Three compounds, three indications, three surrogate successes, three outcome failures.
The one that got approved, and what for
Tesamorelin is the exception, and the shape of its approval is instructive.
Its pivotal 12-month trial randomised 404 people with HIV and excess abdominal fat on antiretroviral therapy, 2:1 to tesamorelin or placebo for the six-month efficacy phase. The primary endpoint was visceral adipose tissue, and VAT fell by 10.9% against 0.6% on placebo. Participants continuing for 12 months saw VAT reduced by approximately 18%, and improvements over the first six months were rapidly lost in those switched to placebo6.
Note the endpoint. Not weight, not strength, not longevity — a specific fat compartment measured by imaging, in a specific population.
The label reinforces it. As of August 2026 the tesamorelin label's Limitations of Use state that long-term cardiovascular safety has not been established, that it is not indicated for weight loss management, and that there are no data to support improved compliance with antiretroviral therapies1.
Our tesamorelin page carries the rest.
What the registry shows about the rest of the class
Search results from ClinicalTrials.gov in August 2026, using each compound name as the query term:
Tesamorelin — 24 registered studies, including two phase 3 records (NCT00123253, enrollment 412, and NCT00608023, enrollment 263).
MK-677 or ibutamoren — 8 registered studies. The largest is NCT00074529, a phase 2 Alzheimer's trial with a listed enrollment of 512. A phase 2 sarcopenia study in post-hip-fracture patients, NCT00128115, listed 83 and is marked terminated.
Ipamorelin — 3 registered studies, of which two are phase 2 post-operative ileus trials with listed enrollments of 320 and 117.
CJC-1295 — 1 registered study, NCT00267527, a phase 2 record in HIV patients with visceral obesity, marked terminated.
Those counts are what the registry returned on that date for those query terms. They are not a claim about every study ever run, and a differently-worded query returns a different set.
The short-term anabolic finding people quote
There is one genuinely positive MK-677 result, and it is worth stating precisely because it is so often stretched.
Eight healthy volunteers underwent periods of caloric restriction. During the second week of each period they received oral MK-677 25 mg or placebo once daily. Mean daily nitrogen balance was +0.31 ± 0.21 g/day on MK-677 against −1.48 ± 0.21 g/day on placebo, p < 0.012.
Eight people. Seven days of drug. A biochemical measure of protein balance, not muscle, not strength, not function. The authors' own conclusion was conditional: *if* these short-term anabolic effects are maintained in patients who are catabolic from disease, it may be useful2. The trials above are what happened when that condition was tested.
What to take from the class
Raising IGF-1 is easy and reproducible. It has been demonstrated in trials with hundreds of participants.
Turning that into a measured clinical outcome has been demonstrated once in this group, for a fat-distribution endpoint, in one population, by one approved compound6.
When a claim about this class reaches you, the question worth asking is which of those two things it is describing. Our page on why most peptide trials are small and short covers why so much of this literature stops at the surrogate, and what happens when a peptide trial fails covers what happened to the compounds that went further.
Frequently asked questions
Do growth-hormone secretagogues actually raise growth hormone and IGF-1?
Yes, consistently. In a 563-patient trial, MK-677 25 mg daily raised serum IGF-1 by 72.9% at twelve months. In a 161-patient hip-fracture trial, MK-0677 raised it by 84% against 17% on placebo. Target engagement is the part of this class that is not in dispute.
Did those IGF-1 increases produce a clinical benefit?
In the trials cited here, no. The 563-patient Alzheimer's trial found no significant differences on any of its four efficacy measures over 12 months. The 161-patient hip-fracture trial found no significant differences in functional performance or overall Sickness Impact Profile score. A 117-patient ipamorelin trial in post-operative ileus reported p = 0.15 on its key endpoint.
Is tesamorelin approved for weight loss?
No. As of August 2026 its label's Limitations of Use state explicitly that it is not indicated for weight loss management, and that long-term cardiovascular safety has not been established. Its approved indication is reduction of excess abdominal fat in adults with HIV-associated lipodystrophy, and its pivotal trial's primary endpoint was visceral adipose tissue measured by imaging.
Is MK-677 a peptide?
No. The paper that first reported its anabolic effect describes it as an orally active nonpeptide mimic of a growth-hormone-releasing peptide. It gets discussed alongside peptides because it acts on the same axis, but it is a small molecule.
How much human data is there on ipamorelin and CJC-1295?
A ClinicalTrials.gov search in August 2026 returned 3 registered studies for ipamorelin — two of them phase 2 post-operative ileus trials with listed enrollments of 320 and 117 — and 1 for CJC-1295, a phase 2 record in HIV patients with visceral obesity that is marked terminated. Those are the counts that query returned on that date, not a claim about every study ever conducted.
References
- DailyMed, U.S. National Library of Medicine (2026). EGRIFTA WR (tesamorelin) for injection — prescribing information. DailyMed Structured Product Label. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=839334d3-8c1d-4c26-9036-2ab524a6ea75
- Murphy MG, Plunkett LM, Gertz BJ, et al. (1998). MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism. The Journal of Clinical Endocrinology and Metabolism. https://pubmed.ncbi.nlm.nih.gov/9467534/
- Sevigny JJ, Ryan JM, van Dyck CH, et al. (2008). Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Neurology. https://pubmed.ncbi.nlm.nih.gov/19015485/
- Bach MA, Rockwood K, Zetterberg C, et al. (2004). The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture. Journal of the American Geriatrics Society. https://pubmed.ncbi.nlm.nih.gov/15066065/
- Beck DE, Sweeney WB, McCarter MD, et al. (2014). Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. International Journal of Colorectal Disease. https://pubmed.ncbi.nlm.nih.gov/25331030/
- Falutz J, Potvin D, Mamputu JC, et al. (2010). Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension. Journal of Acquired Immune Deficiency Syndromes. https://pubmed.ncbi.nlm.nih.gov/20101189/
Medical disclaimer: This content is for general educational purposes only and is not medical advice, diagnosis, or treatment. Always consult a licensed healthcare professional before starting, stopping, or changing any treatment.
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