Ipamorelin: what the molecule is, what the animal and human studies measured, and why development stopped

What ipamorelin is#

Ipamorelin is a synthetic pentapeptide, a chain of five amino acids, with the sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2. Three of the five building blocks are not among the twenty standard amino acids: Aib is alpha-aminoisobutyric acid, D-2-Nal is the D form of 2-naphthylalanine, and the phenylalanine is also in the D form. The chain ends in an amide rather than a free acid.^[1][2] FDA's 2024 review of the compound states that it was first synthesized by researchers at Novo Nordisk in the mid-1990s.^[2]

Ipamorelin is classed as a growth hormone secretagogue: a compound that causes the pituitary gland to release its own growth hormone, rather than supplying growth hormone itself. Compounds of this class act at the growth hormone secretagogue receptor type 1a (GHS-R1a), the same receptor that the stomach hormone ghrelin activates, which is why ipamorelin is often described as a ghrelin mimetic or ghrelin-receptor agonist.^[3][4]

Ipamorelin sequence, molecular weight and CAS number#

The form matters when reading a label. Most research material is supplied as a salt, often the acetate, and a salt carries counter-ion mass that the free peptide does not, so a milligram of acetate powder contains less than a milligram of peptide. FDA's review noted that nominators asking for ipamorelin to be used in compounding were not always clear about which form they meant.^[2] The ipamorelin product page lists these identifiers alongside the lot records for our vials.

Why ipamorelin was studied: selectivity#

By the 1990s, several synthetic growth hormone-releasing peptides (GHRPs) were known, including the hexapeptides GHRP-6 and GHRP-2. They released growth hormone, but in the animal comparisons reported by Novo Nordisk's researchers they also raised ACTH and cortisol, hormones of the stress axis. Ipamorelin came out of that company's chemistry program, and its researchers described it as the first selective compound of this kind.^[3]

Raun et al., European Journal of Endocrinology, 1998#

This is the founding paper. In primary rat pituitary cells, ipamorelin released growth hormone with a potency similar to GHRP-6 and a somewhat lower maximal efficacy; in anesthetized rats its potency and efficacy were comparable to GHRP-6. Antagonist tests indicated that it acted through the same GHRP-type receptor. In conscious swine, the authors compared ipamorelin with GHRP-6, GHRP-2 and other compounds. GHRP-6 and GHRP-2 raised ACTH and cortisol; ipamorelin did not raise either beyond the levels seen with GHRH, even at exposures more than 200 times those that produced half of its maximal growth hormone response. The authors called it the first GHRP-receptor agonist with a selectivity for growth hormone release similar to that of GHRH. All of this work was in cells, rats and pigs.^[3]

Two points are worth keeping in view. The selectivity finding comes from one company's preclinical program, and it describes the conditions tested in those species. It is a statement about which hormones moved in pigs, not a finding about people.

Ipamorelin in animal studies of bone and gut motility#

Svensson et al., Journal of Endocrinology, 2000#

This study asked whether growth hormone secretagogues change bone mineral content in young adult female rats. Over 12 weeks, groups of rats received ipamorelin, GHRP-6, growth hormone or a vehicle control by continuous minipump. All active groups gained body weight and showed higher total tibial and vertebral bone mineral content by dual-energy X-ray absorptiometry (DXA). When bone mineral content was expressed relative to body weight, the difference disappeared. Ex vivo measurements showed that the increase came from larger bone dimensions, while the mineral concentration of the bone was unchanged. The authors interpreted the result as an effect on bone growth and size rather than on bone density.^[5]

Greenwood-Van Meerveld et al., Journal of Experimental Pharmacology, 2012#

Because ghrelin also influences movement of the gut, ipamorelin was later examined in a rat model of postoperative ileus, a temporary slowing of the gut after abdominal surgery. Male rats underwent laparotomy and intestinal manipulation, and gastric emptying was measured as the share of a radiolabeled test meal still in the stomach 15 minutes after it was given. In operated rats that received vehicle, about 78% of the meal remained; in operated rats that received ipamorelin intravenously at the lowest level tested, about 52% remained. In separate organ-bath experiments, surgery reduced the contractile responses of isolated gastric tissue strips, and ipamorelin and ghrelin reversed that reduction. One author was affiliated with Helsinn Healthcare, the company that later sponsored the human trials. The work was in rats and isolated rat tissue.^[4]

Human studies of ipamorelin#

Ipamorelin is one of the few compounds sold as a research peptide that reached controlled human trials. The published human record is small and consists of one pharmacology study and one phase 2 trial.

Gobburu et al., Pharmaceutical Research, 1999#

This was a pharmacokinetic and pharmacodynamic study in healthy male volunteers, eight at each of five escalating levels, each given as a 15-minute intravenous infusion. FDA's review describes it as randomized and placebo-controlled, with six of the eight subjects in each group receiving ipamorelin. The investigators measured plasma ipamorelin and growth hormone and fitted a mathematical model linking the two. They reported linear pharmacokinetics across the levels tested with a terminal half-life of about two hours, and a single episode of growth hormone release that peaked at about 0.67 hours and then declined to negligible levels. The study measured how the molecule moved and how growth hormone responded; it did not assess any clinical outcome.^[6][2]

Beck et al., International Journal of Colorectal Disease, 2014#

Following the rodent motility work, Helsinn sponsored a phase 2 trial in people after bowel surgery (ClinicalTrials.gov NCT00672074). This multicenter, randomized, double-blind, placebo-controlled proof-of-concept study enrolled 117 adults after small or large bowel resection. The primary endpoint was the time from first administration to tolerance of a standardized solid meal. The median was 25.3 hours with ipamorelin and 32.6 hours with placebo, a difference that was not statistically significant (p = 0.15), and the authors reported no significant differences in the key and secondary efficacy analyses. They described the study as small, with a broad range of underlying conditions among participants.^[7]

FDA's 2024 review adds safety detail from the same trial. Serious adverse events occurred in a similar share of each group, and two participants in the ipamorelin group died after resection for colon cancer, both with an anastomotic leak. FDA noted that it is unclear whether those deaths were related to ipamorelin, but stated that they raise safety concerns about its use in compounding.^[2]

A second phase 2 trial, and the end of development#

A second Helsinn-sponsored phase 2 study (NCT01280344) compared three ipamorelin regimens with placebo in adults scheduled for open bowel resection and is listed in the registry as completed.^[8] No published results for it were found in the sources reviewed for this page. FDA's review quotes a 2020 literature review stating that, because of disappointing results, ipamorelin's development was discontinued, and it confirms that ipamorelin is not a component of any FDA-approved drug.^[2]

What has not been studied about ipamorelin#

The gaps are large for a compound with this much search interest. FDA's 2024 review states that it did not identify published acute or repeated-exposure toxicity, genotoxicity or carcinogenicity studies for either form, found no ipamorelin-specific reproductive or developmental toxicity studies, and concluded that the available nonclinical studies were too limited in scope and duration to inform safety.^[2]

• No long-term human data: the published human exposure is a single-session pharmacology study and a trial lasting up to about a week.
• The growth hormone selectivity over ACTH and cortisol was shown in pigs; the human studies summarized here did not report it as a measured outcome.
• The bone findings come from one rat study and describe bone size, not density.
• The motility findings in rats were not confirmed by the published human trial, which did not meet its primary endpoint.
• No approved medicine containing ipamorelin was identified; FDA found it is not a component of any FDA-approved drug and found no monograph in the pharmacopoeias it searched.

Research supplied as a two-peptide vial is a separate question again. Our article on CJC-1295 and ipamorelin covers the blend, which has never been studied as a combination, and the CJC-1295 + Ipamorelin product page lists that vial. For how ipamorelin compares with peptides that act at the GHRH receptor instead, see ipamorelin vs sermorelin and ipamorelin vs tesamorelin.

Regulatory status of ipamorelin#

FDA lists ipamorelin acetate in category 2 under its 503B interim policy for outsourcing facilities, the category for bulk substances that may present significant safety risks; FDA gives September 29, 2023 as the date it was added to that category. The agency cites a possible risk of immunogenicity from aggregation or peptide-related impurities, the added complexity of characterizing a peptide with unnatural amino acids, and a literature report of serious adverse events including death when ipamorelin was given intravenously for gastric motility. Ipamorelin acetate also appears in the same page's table of nominations that were withdrawn.^[9] FDA's 2024 briefing document for its Pharmacy Compounding Advisory Committee stated that the evaluation criteria weighed against placing either form on the 503A bulk substances list.^[2]

In sport, the World Anti-Doping Agency's 2026 Prohibited List names ipamorelin among the growth hormone secretagogues in class S2, peptide hormones and related substances, which are prohibited at all times, in and out of competition.^[10] FDA's review also notes that Australia added ipamorelin to its Poisons Standard as a performance and image enhancing drug.^[2]

Reading an ipamorelin listing and COA#

A listing that leans on the word "selective" is borrowing a conclusion from pig studies published in 1998. A listing that states the sequence, the form (free peptide or acetate), the amount per vial, the lot number and where the lot's analytical report can be read is describing a reagent. For ipamorelin, the mass spectrometry result should be consistent with 711.9 g/mol for the free peptide (the protonated ion appears near 712.4), and the HPLC chromatogram should show one main peak with the purity figure the label claims. Our guide to reading a Certificate of Analysis covers the report format, and the COA library lists every Renuvia lot and its current testing status.