Growth hormone secretagogues: what the human trials show, and what to watch

What these compounds are

All seven make the pituitary gland release more of the body's own growth hormone (GH), which in turn raises IGF-1, the hormone that carries much of GH's effect. They reach the pituitary by two different routes.

• GHRH analogs copy the hypothalamus's own growth-hormone-releasing hormone. Tesamorelin is a "growth hormone releasing factor analog", and CJC-1295 is a long-acting version built to last for days.^22,19
• Ghrelin mimetics act on the ghrelin receptor, the hunger hormone's receptor, which also triggers GH release. They include MK-677 (ibutamoren, taken by mouth), ipamorelin, GHRP-2, GHRP-6 and hexarelin.^1,6

Which route a compound uses explains several of the side effects below. The ghrelin receptor is also involved in appetite and in the stress-hormone axis. Several ghrelin mimetics raise cortisol, prolactin or hunger along with GH.

What the human trials measured

MK-677 (ibutamoren)

MK-677 has the most human data of the unapproved compounds. In a randomized, placebo-controlled trial, 65 healthy adults aged 60 to 81 took MK-677 or placebo daily. At 12 months, 24-hour growth hormone was 1.8 times baseline and IGF-1 1.5 times. Fat-free mass rose 1.1 kg on MK-677 and fell 0.5 kg on placebo. Visceral fat and total fat mass didn't change, and the authors write that the extra lean mass "did not result in changes in strength or function."¹

The metabolic cost showed up in the same trial. Fasting glucose rose an average of 5 mg/dL (0.3 mmol/L). HbA1c rose 0.2 points against a 0.1-point fall on placebo. Insulin sensitivity fell, and 24-hour cortisol rose by 47 nmol/L. Body weight went up 2.7 kg on MK-677 against 0.8 kg on placebo.¹ An earlier four-week study in older adults found fasting glucose rising from 5.4 to 6.8 mmol/L,² and an eight-week trial in obese men found impaired glucose tolerance on testing even though fasting glucose didn't change.⁵

A larger trial tested MK-677 in 123 older adults recovering from hip fracture. It "was terminated early due to a safety signal of congestive heart failure," and the authors concluded the drug "has an unfavorable safety profile in this patient population."³ FDA's 2024 review of the trial counts four cases of heart failure on MK-677 (6.5%) against one on placebo (1.7%), and a mean rise in systolic blood pressure of 12 to 16 mmHg on the drug.⁴

Ipamorelin

Ipamorelin is often described as the "clean" secretagogue, one that releases GH without raising cortisol. That finding comes from a 1998 study in which the selectivity testing was done in pigs: ipamorelin didn't raise ACTH or cortisol even at very high doses, while GHRP-2 and GHRP-6 did.⁶ We found no published human study that measured cortisol or prolactin on ipamorelin. A human dosing study in healthy men found a half-life of about two hours and a single GH pulse after each infusion.⁷

Ipamorelin's only published human efficacy trial tested it intravenously after bowel surgery, to speed recovery of gut function. There were "no significant differences between ipamorelin and placebo" on any efficacy measure.⁸ FDA's 2024 review notes two deaths among ipamorelin-treated patients in that trial, from surgical complications, and says it is unclear whether they were related to the drug.⁹

GHRP-2

In seven lean, healthy men, a GHRP-2 infusion made them eat 35.9% more at a buffet meal than saline did, and every participant ate more.¹⁰ A follow-up study in lean and obese adults found the effect was dose-dependent: 10% more food at a low dose and 34% more at a high dose.¹¹ GHRP-2 also raised prolactin, ACTH and cortisol in healthy young adults, to the same degree as hexarelin.¹² Taken daily, the GH response faded quickly. Peak GH fell from 83 to 51 µg/L between day 1 and day 5, and IGF-1 didn't rise over five days.¹³

GHRP-6

GHRP-6 was the first of these peptides tested in people. In 18 healthy men it produced a dose-dependent GH rise, and at the highest dose prolactin and cortisol rose about twofold.¹⁴ GHRP-6 is widely said to cause strong hunger. We found no human study that measured appetite or food intake on GHRP-6. The human food-intake data in this guide are for GHRP-2 and MK-677. FDA's safety summary for GHRP-6 points to possible effects on cortisol and to higher blood glucose from reduced insulin sensitivity.²⁴

Hexarelin

Hexarelin is among the most potent GH releasers in this group: in 12 men, peak GH rose with the dose up to a near-maximal response at 2 µg/kg.¹⁵ It also raised prolactin by up to 180% and cortisol by about 40% after single doses.¹⁶ Taken twice daily for 16 weeks, though, its GH effect wore down to about half, and it recovered after a month off. IGF-1, body fat, lean mass and bone density didn't change significantly.¹⁷ Cortisol and prolactin didn't stay raised over the same 16 weeks.¹⁸

CJC-1295

A single injection of CJC-1295 in healthy adults raised GH 2- to 10-fold for six days or more and IGF-1 1.5- to 3-fold for 9 to 11 days. Its half-life was about six to eight days.¹⁹ FDA's 2024 review of the full papers counts injection-site reactions in about 70% of people on the drug, and headache in 63% against 14% on placebo. Flushing, warmth and brief drops in blood pressure occurred in 30% on the drug and none on placebo. Flushing was more common at higher doses.²⁰

A phase 2 trial of CJC-1295 in people with HIV is listed on ClinicalTrials.gov as terminated, with no reason given and no results posted.²¹ FDA's review describes a reported death in that trial, citing news accounts it calls anecdotal, and notes that the trial's data were never published.²⁰ CJC-1295 is often sold combined with ipamorelin. We found no published human trial of that combination; the PubMed records that mention both are reviews.

Tesamorelin

Tesamorelin is the only one of these with FDA approval and the large trials that come with it. In 412 adults with HIV-associated belly fat, 26 weeks of tesamorelin cut visceral fat by 15.2%, while it rose 5.0% on placebo. IGF-1 rose 81%.²³ The label says it is "not indicated for weight loss management as it has a weight neutral effect," and that its long-term cardiovascular safety hasn't been established.²²

The label also shows how often GH-type side effects turn up when a GH-releasing drug is tested at scale. After 26 weeks, 47% of patients had IGF-1 above 2 standard deviations of normal and 36% above 3. HbA1c of 6.5% or higher, the diabetes threshold, developed in 5% of patients against 1% on placebo.²²

What to watch

Blood sugar and insulin sensitivity

Growth hormone works against insulin, and this is the most consistent signal across the group. MK-677 raised fasting glucose and HbA1c and lowered insulin sensitivity over a year.¹ It impaired glucose tolerance within eight weeks in obese men.⁵ Tesamorelin raised the odds of reaching a diabetic HbA1c, and its label says to check glucose status before starting and to monitor during treatment.²² FDA's safety summaries flag higher blood glucose with GHRP-6 and a higher insulin requirement in patients given GHRP-2.²⁴ Fasting glucose and HbA1c are the numbers that show this change.

Water retention, aches and numbness

Tesamorelin's label explains the mechanism: fluid retention "is thought to be related to the induction of GH secretion." It shows up as "increased tissue turgor and musculoskeletal discomfort," which leads to swelling, joint pain and carpal tunnel syndrome. The label says these effects are "either transient or resolve with discontinuation."²² Carpal tunnel syndrome is pressure on the nerve at the wrist, felt as numbness or tingling in the thumb and fingers. The rates on the label are small but consistently higher than placebo: tingling 5% against 2%, numbness 4% against 2%, carpal tunnel syndrome 1% against none.

MK-677 trials recorded swelling and muscle pain more often on the drug than on placebo, though not to a statistically significant degree in the 12-month trial.¹ FDA's review notes more edema and fluid overload on MK-677 in hip-fracture patients, and individual reports of carpal tunnel syndrome and short-lived hand numbness in other trials.⁴ In older people, or anyone with heart disease, fluid retention is more than a nuisance. It is the context for the heart-failure signal above.³

Cortisol and prolactin

GHRP-2, GHRP-6 and hexarelin raised cortisol, ACTH and prolactin after single doses in healthy people.^12,14,16 Hexarelin's prolactin rise was the largest, up to 180% above baseline.¹⁶ With hexarelin taken for 16 weeks, the rises did not persist.¹⁸ MK-677 raised 24-hour cortisol over 12 months in older adults¹ but not over eight weeks in obese men,⁵ and it raised prolactin by about a quarter, within the normal range.² What higher cortisol or prolactin means over months to years of use hasn't been studied in these compounds.

Appetite

Ghrelin is the hunger hormone, so drugs that act on its receptor can increase appetite. In human studies, GHRP-2 raised how much people ate by about a third.^10,11 On MK-677, 67% reported more appetite against 36% on placebo, and for half of them it settled within three months.¹ GHRP-6's reputation for hunger rests on its mechanism and on reports from people who have used it, not on a human trial we could find.

The response fades

With GHRP-2 and hexarelin, repeated dosing blunted the GH response within days to weeks.^13,17 A review by GHRP-2's developers notes that whether the response wears down "depends in part on the dosage and frequency of administration."³⁰ Short studies that show a big GH spike after a first dose can overstate what happens with ongoing use.

Who the evidence says should skip them

These are groups in whom a label or a trial found a specific risk. The list isn't complete, and it isn't a substitute for a clinician who knows your history.

FDA status, compound by compound

FDA approval means trials reviewed by FDA showed a drug safe and effective for a specific use, and that it is made to FDA-checked quality standards. While it decides which ingredients pharmacies may compound with, FDA keeps an interim list of those that "may present significant safety risks" (Category 2), for state-licensed pharmacies (503A), outsourcing facilities (503B) or both.²⁴

On October 30, 2026, the Department of Health and Human Services published a draft policy saying it won't take enforcement action against 503A pharmacies compounding certain peptides while FDA builds its list by rulemaking.²⁸ The appendix to that policy names six peptides: BPC-157, Epitalon, KPV, MOTS-c, Semax and TB-500. None of the compounds in this guide are on it. A committee vote is advice to FDA rather than a rule, and FDA's lists change. The dates on each source below are when we checked them.

What isn't known

• Long-term safety. Apart from tesamorelin, no compound here has a controlled trial longer than about a year. Tesamorelin's own label says the effects of prolonged IGF-1 elevation are unknown and its long-term cardiovascular safety isn't established.²²
• Benefit in healthy younger adults. The trials were in older adults, people with HIV, surgical patients or people with GH problems. None tested muscle, recovery or performance in the healthy younger adults who most often use these compounds.
• Ipamorelin's hormone profile in people. The no-cortisol finding is from pigs.⁶
• GHRP-6 and appetite in people. We found no human measurement.
• Combinations. We found no published human trial of CJC-1295 with ipamorelin or any other stack.
• What's in the vial. Every trial here used a pharmaceutical-grade product. FDA's compounding listings point to immunogenicity and impurity risks for several of these peptides.²⁴ Products sold outside pharmacies haven't been tested at all.

Each compound's page in the PeptideHelp database has its own sources and safety notes. We'll update this guide as FDA's lists or the evidence change.