Ipamorelin: what we know and what we don't

A five amino acid chain from Novo Nordisk

Ipamorelin is a small synthetic peptide, five amino acids long (Aib-His-D-2-Nal-D-Phe-Lys-NH2), that contains unnatural amino acids (Raun et al. 1998). It switches on the ghrelin receptor (GHS-R1a) and makes the pituitary gland release a pulse of growth hormone (Beck et al. 2014).

Novo Nordisk developed the molecule and published most of the early research (Raun et al. 1998). Later, Helsinn Therapeutics took it into clinical trials for a completely different purpose: helping the gut start working again after bowel surgery (NCT00672074). It belongs to the family of growth hormone releasing peptides, alongside GHRP-2, GHRP-6 and hexarelin (Raun et al. 1998).

It is marketed for weight loss, anti-aging, sleep and bodybuilding, as injections, nasal sprays and oral forms (FDA briefing 2024). That marketing rests on a very thin evidence base.

One dosing study in healthy men

The only human pharmacology study gave ipamorelin as a single 15 minute intravenous infusion to healthy men at five dose levels, from 4.2 to 140 nmol/kg (Gobburu et al. 1999). Each dose level had 8 subjects. Every dose level produced a single growth hormone pulse, peaking at about 0.67 hours. The half-life of ipamorelin was about 2 hours.

That is the entire human evidence for "ipamorelin raises GH." One study, single IV doses, in a small group of men.

Nobody has published data on subcutaneous injection, on daily use beyond a week, or on IGF-1 levels over weeks of use.

The "no cortisol" claim comes from pigs

A selling point you will hear everywhere is that ipamorelin is "selective," meaning it raises growth hormone without touching cortisol or prolactin.

The cortisol part was shown in pigs. Ipamorelin did not raise ACTH or cortisol even at more than 200 times the dose needed for GH release, while GHRP-2 and GHRP-6 did raise them. In the same pigs, none of the three raised prolactin (Raun et al. 1998). The prolactin finding is not specific to ipamorelin. No published human study has confirmed the cortisol selectivity.

The clinical trial failed

Helsinn ran two phase 2 trials testing intravenous ipamorelin in patients recovering from bowel surgery.

The published trial enrolled 117 patients (114 analysed, 56 on ipamorelin) who received 0.03 mg/kg IV twice daily for up to 7 days after bowel resection. The primary outcome was time to first tolerated meal. Result: a median of 25.3 hours on ipamorelin versus 32.6 hours on placebo, p = 0.15 (Beck et al. 2014, NCT00672074). That is not a statistically significant difference. No secondary measure was significant either.

A larger trial enrolled 320 patients in three ipamorelin dose groups (0.03 mg/kg twice daily, 0.06 mg/kg twice daily, 0.06 mg/kg three times daily) and a placebo group (NCT01280344). It was completed in 2014. No results have ever been posted or published. No later trial is registered.

What nobody has measured

The reasons most people inject ipamorelin (muscle growth, fat loss, better sleep, anti-aging) have never been tested in any human study. Not once.

No trial has measured lean mass, fat mass, strength, body composition, sleep quality or any marker of aging. The longest anyone has received ipamorelin under clinical supervision is 7 days, by IV drip, in a hospital bed after surgery (Beck et al. 2014). The weeks or months of daily subcutaneous injections that people do at home are a completely unstudied use pattern.

Is it approved?

No, nowhere. Ipamorelin is not approved by the FDA, EMA or any other regulator for any purpose (FDA briefing 2024).

Two compounding pharmacies asked the FDA to allow ipamorelin in pharmacy compounding. The FDA reviewed the request and proposed saying no, citing missing quality data, safety concerns and no evidence it works (FDA briefing 2024).

On 29 October 2024, the FDA's Pharmacy Compounding Advisory Committee voted 0 yes, 12 no, 1 abstain against adding ipamorelin (both free base and acetate) to the 503A bulk drug substances list (FDA PCAC summary minutes, Oct 2024).

Doses used in the studies

These are the doses the researchers used, not recommendations.

The phase 1 study gave single IV infusions of 4.2 to 140 nmol/kg over 15 minutes (Gobburu et al. 1999). The phase 2 surgical trials used 0.03 mg/kg IV twice daily for up to 7 days, and the larger trial also tested 0.06 mg/kg twice daily and 0.06 mg/kg three times daily (Beck et al. 2014, NCT01280344).

No published human study has used subcutaneous injection at any dose.

Safety

In the 114 patient surgery trial, overall adverse events were reported in 87.5% of ipamorelin patients and 94.8% on placebo. Serious adverse events occurred in 17.9% on ipamorelin and 15.5% on placebo, mostly infections and surgical complications (Beck et al. 2014).

Side effects seen more often on ipamorelin than placebo included low potassium (12.5% vs 3.4%), insomnia (10.7% vs 5.2%) and high blood sugar at discharge (14.3% vs 8.6%). Nausea and vomiting occurred at similar rates in both groups (FDA briefing 2024).

Two patients on ipamorelin died, both after bowel cancer surgery with anastomotic leaks. Whether ipamorelin played any role is unclear (Beck et al. 2014, FDA briefing 2024). The FDA briefing notes that "serious adverse events including fatal SAEs were observed in the study", raises concerns about immunogenicity and impurities, and states there are no safety data for subcutaneous use (FDA briefing 2024).

The longest human exposure is 7 days IV. There is zero human data on what weeks or months of subcutaneous use does.

A doping lab analysis of black-market growth products found gly-ipamorelin, a modified ipamorelin with an extra amino acid (Krug et al. 2018). What you think you are injecting and what is in the vial may not be the same thing.

The straight picture

Roughly 470 people have enrolled in ipamorelin studies and an estimated 320 received the drug, by IV, for a week at most (Gobburu et al. 1999, Beck et al. 2014, NCT01280344). NCT01280344 never reported its group sizes. The one published clinical trial did not show a benefit. The claim that it spares cortisol comes from pigs (Raun et al. 1998). Muscle, fat, sleep and anti-aging effects have never been measured in any human.

Missing data is not proof it does nothing. The studies people would need have not been done, and no trial is registered beyond the two from 2009 and 2014.

Sources

1. Gobburu et al. 1999, PK and PD of ipamorelin in human volunteers. Phase 1 dose-escalation in healthy men, 8 per dose level, 5 levels, single IV infusion.
2. Beck et al. 2014, Phase 2 trial of ipamorelin for postoperative ileus. Randomized placebo-controlled trial, 117 enrolled, 114 analysed, bowel resection patients, IV dosing up to 7 days.
3. NCT01280344, Safety and efficacy of ipamorelin for recovery of gastrointestinal function. Phase 2 trial, 320 patients, 4 arms, completed 2014, no results posted.
4. Raun et al. 1998, Ipamorelin: the first selective growth hormone secretagogue. Preclinical study in rat cells, rats and pigs; in pigs, no ACTH or cortisol rise with ipamorelin.
5. NCT00672074, Safety and efficacy of ipamorelin for management of post-operative ileus. Phase 2 trial, 117 patients, completed.
6. FDA briefing document on ipamorelin, October 2024. FDA staff review of safety and regulatory history.
7. FDA PCAC summary minutes, 29 October 2024. Advisory committee vote: 0 yes, 12 no, 1 abstain against 503A listing.
8. Krug et al. 2018, Analysis of new growth promoting black market products. Lab analysis of black-market products; found gly-ipamorelin, gly-GHRP-2 and gly-GHRP-6.