Capromorelin: The Growth Hormone Secretagogue That Got Approved, Just Not for People

Growth hormone secretagogues have a thin regulatory record. Most reached phase 2 and stopped. Capromorelin is the exception, and the exception took an unusual route: it holds a US approval as a veterinary medicine while its human programme ended.

That split makes it the best-evidenced compound in its class. Randomised placebo-controlled trials exist in dogs and in cats, long-term safety data run to months of daily dosing, and published work covers at least nine species including humans.

One finding runs through all of it, and it is the reason to read the compound carefully rather than as an appetite story: wherever the appetite effect appears, a glucose effect appears with it.

Chemical identity

A non-peptide small molecule, despite acting at a receptor whose natural ligand is a 28-residue peptide.

Kimera supplies the material as Capromorelin.

Reading the structure

A fused pyrazolone-piperidine bicycle sits at one end, carrying a benzyl group at the ring-fusion carbon. A benzyl ether hangs off the side chain, and a 2-amino-2-methylpropanamide caps the other end. Two defined stereocentres fix the geometry.

Nothing about it resembles ghrelin. That is the interesting part, and the next section explains why it matters for anyone designing an experiment.

Why a non-peptide agonist matters

Ghrelin is a peptide, and peptide agonists at its receptor need parenteral administration. A small molecule does not.

Oral activity is what made the veterinary approval practical, and it is what separates this compound from the peptide agonists in the same class such as Hexarelin and GHRP-6. The receptor is shared. The delivery problem is not.

The receptor and the class

Growth hormone release runs through a G-protein coupled receptor, GHSR-1a, expressed in the hypothalamus and elsewhere [1].

What GHSR-1a does

Ghrelin, released from the stomach, is the endogenous ligand. Beyond appetite and growth hormone release it touches gut motility, gastric acid secretion, taste, circadian rhythm, glucose metabolism and more [1]. A receptor with that breadth does not produce a clean single effect when an agonist engages it.

The class is crowded and mostly unapproved

Capromorelin sits alongside macimorelin, tabimorelin, and the peptide agonists. Analytical work characterising metabolites treats the three non-peptide mimetics together as a group [2].

Related compounds in the catalogue include MK-777, an ester of a different secretagogue. Mechanistic proximity does not make them interchangeable in an experiment.

The 2009 human trial

The human record is one large study, and its result is more interesting than its reputation suggests.

What it measured

A randomised, double-masked, placebo-controlled multicentre trial enrolled 395 adults aged 65 to 84 with mild functional limitation, across four dosing schedules plus placebo, intended to run two years [3].

It stopped early under predetermined treatment-effect criteria. Even so, 315 participants completed six months and 284 completed twelve.

What it found

IGF-I rose in a sustained, dose-related way across all active groups. Peak nocturnal growth hormone rose, and notably the rise was greatest on the least frequent dosing schedule.

At six months, body weight rose 1.4 kg against a 0.2 kg fall on placebo. Lean body mass rose 1.4 kg against 0.3 kg. Tandem walk improved by 0.9 seconds. By twelve months stair climb had improved as well [3].

What it also found

Adverse events were fatigue, insomnia, and increases in fasting glucose, glycosylated haemoglobin, and indices of insulin resistance [3].

Hold that last item. It reappears in a different species below, measured by a different group with a different method, and the agreement between them is the most useful thing in this literature.

The veterinary approvals

An oral solution received US approval for dogs in 2017 [12]. A separate product addresses weight loss in cats.

The dog trial

A prospective, randomised, masked, placebo-controlled study enrolled 244 client-owned dogs reported inappetent for at least two days, with 177 in the effectiveness analysis [5]. Owners assessed appetite at day 0 and day 3.

A separate laboratory study in healthy Beagles measured food consumption and body weight over four consecutive days of dosing [4]. Long-term daily oral safety in dogs has its own published evaluation [7], and a review covers the discovery and development route [6].

The cat trial

A 2025 multicentre randomised masked placebo-controlled field study enrolled 176 client-owned cats with chronic kidney disease and unintended weight loss of 5% or more, randomised 2:1, dosed once daily for 55 days [8].

In the effectiveness population of 112, mean body weight change from day 0 to day 55 was +5.18% on drug against -1.65% on placebo. The treatment effect was +6.81%, with a confidence interval of 4.21 to 9.42.

That is a well-powered result over 55 days, which makes it the strongest single efficacy dataset the compound has in any species.

The glucose signal travels with the appetite effect

This is the through-line, and it holds across the two species where anyone looked properly.

In humans

The 2009 trial recorded increases in fasting glucose, glycosylated haemoglobin, and insulin resistance indices alongside the body composition gains [3].

In cats

A dedicated study dosed seven healthy cats with Capromorelin for 30 days [9]. After the first day fasting blood glucose rose by 13 mg/dL and insulin fell. An intravenous glucose tolerance test showed blunting of the first-phase insulin response, from 17,437 to 4,931 ng/L per 15 minutes.

At day 30 the first-phase response was still blunted at 9,993 ng/L per 15 minutes. The effect attenuated without disappearing.

Why this is the finding worth carrying

Two species, two research groups, two decades apart, two different measurement approaches, and the same direction of effect on glucose handling.

The proposed mechanism is coherent. GHSR-1a sits on pancreatic delta cells, and agonism there affects somatostatin signalling, which feeds back onto insulin secretion [9]. This is receptor pharmacology rather than an incidental finding.

For experimental design the implication is direct. Any study using this compound in a metabolic model needs glucose endpoints, because the compound moves them whether or not they are the subject.

Where the effect does not appear

Negative results are thin on the ground in this literature, which makes the ones that exist worth naming.

The rabbit disagreement

Two published studies dosed rabbits and disagreed. One compared capromorelin against mirtazapine for appetite in New Zealand White rabbits [10]. Another tested four prokinetic drugs including this one in healthy New Zealand rabbits and found no increase in fecal output or food intake [11].

The second used a single dose in a crossover design. The first ran a comparison against an active drug. Different designs answering different questions is the ordinary explanation, and neither result cancels the other.

The species range is unusually wide

Very few research compounds have a comparative dataset this broad. It exists because appetite stimulation has veterinary value across production and companion species, not because anyone set out to build a phylogenetic comparison.

What the breadth is good for, and what it is not

As a source of cross-species pharmacology this is genuinely useful. The receptor is conserved, the direction of effect is consistent in mammals and birds, and the compound is orally active in all of them.

As a basis for predicting a new species it is weaker than it looks. The rabbit results already disagree with each other, and the avian studies are small. Breadth of species is not depth of evidence, and the two get confused because a long list reads as thorough.

Analytical chemistry

Detection work treats Capromorelin alongside macimorelin and tabimorelin, characterising metabolites as potential markers [2]. That work exists for doping control, where the relevant question is whether an administered compound can be shown after the parent has cleared.

For laboratory verification the useful consequence is that metabolite profiles for this compound are published rather than inferred.

Why that matters more than it sounds

Most catalogue compounds have no published metabolite map. Detection then depends on finding the parent, which limits the useful window to hours.

A characterised metabolite extends that window. It also gives a second identity check: a sample producing the parent mass but none of the expected metabolites in a biological system is worth a second look.

The class shares a detection problem

The three non-peptide mimetics are structurally related, and their metabolites overlap [2]. A method tuned for one can respond to another.

That is why the published work characterises all three together rather than singly. Anyone adapting a method from that literature should keep the comparators in the run.

The regulatory split is the useful context

One molecule, two outcomes, and the difference is not about the chemistry.

What the human programme produced

The 2009 trial met several endpoints. Lean mass rose, two physical performance measures improved, and IGF-I tracked dose [3]. It still stopped early, and no human approval followed.

What the veterinary programme produced

Approval for dogs in 2017 [12], a cat product, and a decade of clinical use since. The trials behind it are smaller than the human one and more decisive.

Reading the difference honestly

The gap is not evidence that the compound works in dogs and fails in people. Both programmes showed the compound doing what its mechanism predicts.

What differs is the bar. An appetite stimulant for an inappetent dog is judged against a short, clear endpoint. A drug for age-related functional decline in humans is judged against a longer, harder one, with the glucose findings weighing on the other side of the ledger [3].

The compound is the same. The question asked of it was not.

How to read a Capromorelin study

Four questions separate a transferable result from a species-specific one.

Which species?

Capromorelin is approved for dogs and studied across at least nine species. A dog dose and a macaque dose are not the same experiment, and the rabbit literature already disagrees with itself [10][11].

Which endpoint?

Owner-assessed appetite [5], measured food consumption [6], and body weight over 55 days [8] are three different measures. The first is subjective by design and appropriate for its purpose.

Over what duration?

Effects change with time. The cat glucose work shows first-phase insulin blunting attenuating between day 1 and day 30 without resolving [9]. A single-day result and a 30-day result describe different states.

Was glucose measured?

If not, the study has an uncontrolled variable, given the human and feline findings [3][9].

This applies well beyond metabolic work. Appetite, activity and body composition all interact with glucose handling, so a study measuring any of those without a glucose endpoint has left a known effect unobserved.

Was the comparator active or placebo?

Both appear in this literature and they answer different questions. The dog and cat trials used placebo controls [5][8]. The rabbit and budgerigar work compared against mirtazapine and cyproheptadine [10][14].

An active comparator tells you which drug performed better in that setting. It does not establish that either beat no treatment. Reading a comparative result as an absolute one is the most common error this literature invites.

Verifying research material

Capromorelin is a defined chemical entity with published identifiers, so verification is arithmetic rather than judgement. Batch documentation sits on the certificates of analysis page.

Identity

Formula C₂₈H₃₅N₅O₄, molecular weight 505.6, InChIKey KVLLHLWBPNCVNR-SKCUWOTOSA-N. Mass spectrometry should land near 505.6, and CP-424391 is the development code that appears in older literature.

Stereochemistry

Two defined stereocentres carry the activity, and mass spectrometry cannot see either. A diastereomer shares the formula and the mass exactly.

Chiral chromatography against a reference standard is the check that answers it. For a small molecule this is more tractable than the equivalent problem in a peptide, where hydrolysis and amino acid analysis are needed.

Handling

A small molecule of this size is more forgiving than the peptide agonists in the same class. It does not carry the photodegradation and proteolysis liabilities that make GHRP-6 and its relatives awkward to store.

Ordinary practice applies. Keep it dry, cold and dark, and treat solutions as having a shorter life than the solid.

The amide bonds are the hydrolysis risk. Both flank the pyrazolinone core, and aqueous solutions at extreme pH will cleave them over time. Buffer near neutral if a stock has to sit.

What a certificate should show

Three numbers and one technique. Mass near 505.6, a purity figure with its method named, and a chromatographic trace rather than a bare percentage.

Ask whether the method separates diastereomers. Many routine purity assays do not, and Capromorelin has two stereocentres to get wrong. A certificate reporting 99% by a method blind to stereochemistry is answering a narrower question than it appears to.

Common questions about Capromorelin

Class and approval status

Is Capromorelin a SARM? No. It is a ghrelin receptor agonist and growth hormone secretagogue, acting at GHSR-1a. It has no androgen receptor activity, and the two mechanisms are unrelated.

Is it approved? Yes, as a veterinary medicine in the US, with an oral solution approved for dogs in 2017 [12] and a product for weight loss in cats [8]. It holds no human approval.

What happened in the human trial? It ran 395 adults aged 65 to 84, stopped early under predetermined treatment-effect criteria, and still showed gains in lean mass, body weight and two physical performance measures at six and twelve months [3].

Mechanism and evidence

Why does it need no injection? It is a non-peptide small molecule, unlike ghrelin itself and unlike the peptide agonists in the class.

Does it affect blood sugar? Yes, in both species where it was measured properly. Fasting glucose rose and insulin responses blunted in humans [3] and in cats [9].

What is CP-424391? The development code, from the original human programme. Older papers use it.

Why did the human trial stop if the results were positive? The published account says only that it ended under predetermined treatment-effect criteria [3]. The paper does not elaborate, and nothing else in the indexed literature does either. Treat any confident explanation as inference.

Is it related to MK-677? Same receptor, same class, different molecule. Both are non-peptide growth hormone secretagogues at GHSR-1a. Neither is an androgen receptor modulator, despite how the two are often filed together.

Which species has the strongest data? Cats, on current evidence. The 176-cat trial ran 55 days with a placebo control and a clear weight endpoint [8]. The dog data are larger in total but shorter per study.

Does it raise growth hormone directly? It triggers release rather than supplying hormone. The 2009 trial measured a rise in peak nocturnal growth hormone, largest on the least frequent dosing schedule [3].

Why does dosing frequency change the growth hormone response? Receptor desensitisation is the usual explanation for that pattern. The trial observed it; it did not test the mechanism [3].

Analysis

Is there a published metabolite profile? Yes, characterised alongside macimorelin and tabimorelin [2]. That is unusual for a compound at this scale and useful for identity work.

Summary of the evidence

Strongest evidence: the veterinary trials. A 176-cat randomised placebo-controlled study over 55 days with a +6.81% treatment effect on body weight [8], a 244-dog randomised placebo-controlled study [5], supporting laboratory work in Beagles [6], and a dedicated long-term safety evaluation [7]. Alongside that, a 395-participant human trial with body composition and physical function endpoints [3].

Also strong, and easy to overlook: the glucose finding, replicated across humans [3] and cats [9] by different groups using different methods.

Weakest evidence: everything outside dogs, cats and humans. The macaque [12], poultry [13] and avian [14][15] studies are small. The two rabbit studies disagree [10][11].

Read plainly, Capromorelin is the best-evidenced growth hormone secretagogue available, and the evidence says two things at once. Capromorelin increases appetite, weight and lean mass across species. It also moves glucose handling in the same direction every time anyone measures it.

The rest of this class sits in the endocrine category.

Status: supplied for laboratory research use only.

References

1. Rathore M, Das N, Ghosh N, Guha R. Insights on discovery, efficacy, safety and clinical applications of ghrelin receptor agonist capromorelin in veterinary medicine. Vet Res Commun. 2024;48(1):1-10. PMID 37493940. DOI
2. Lange T, Thomas A, Görgens C, Bidlingmaier M, Schilbach K, Fichant E, Delahaut P, Thevis M. Comprehensive insights into the formation of metabolites of the ghrelin mimetics capromorelin, macimorelin and tabimorelin as potential markers for doping control purposes. Biomed Chromatogr. 2021;35(6):e5075. PMID 33458843. DOI
3. White HK, Petrie CD, Landschulz W, MacLean D, Taylor A, Lyles K, Wei JY, Hoffman AR, et al. Effects of an oral growth hormone secretagogue in older adults. J Clin Endocrinol Metab. 2009;94(4):1198-1206. PMID 19174493. DOI
4. Zollers B, Rhodes L, Heinen E. Capromorelin oral solution (ENTYCE) increases food consumption and body weight when administered for 4 consecutive days to healthy adult Beagle dogs in a randomized, masked, placebo controlled study. BMC Vet Res. 2017;13(1):10. PMID 28056951. DOI
5. Zollers B, Wofford JA, Heinen E, Huebner M, Rhodes L. A prospective, randomized, masked, placebo-controlled clinical study of capromorelin in dogs with reduced appetite. J Vet Intern Med. 2016;30(6):1851-1857. PMID 27859746. DOI
6. Rhodes L, Zollers B, Wofford JA, Heinen E. Capromorelin: a ghrelin receptor agonist and novel therapy for stimulation of appetite in dogs. Vet Med Sci. 2018;4(1):3-16. PMID 29468076. DOI
7. Zollers B, Huebner M, Armintrout G, Rausch-Derra LC, Rhodes L. Evaluation of the safety in dogs of long-term, daily oral administration of capromorelin, a novel drug for stimulation of appetite. J Vet Pharmacol Ther. 2017;40(3):248-255. PMID 27665742. DOI
8. Wofford JA, Milliken MacKinnon A, Heinen E. Capromorelin promotes weight gain in cats with unintended weight loss: a randomized, masked, placebo-controlled clinical trial. J Feline Med Surg. 2025;27(11):1098612X251379924. PMID 41204815. DOI
9. Pires J, Greathouse RL, Quach N, Huising MO, Crakes KR, Miller M, Gilor C. The effect of the ghrelin-receptor agonist capromorelin on glucose metabolism in healthy cats. Domest Anim Endocrinol. 2021;74:106484. PMID 32619812. DOI
10. Draper JM, Savson DJ, Lavin ES, Feldman ER, Singh B, Martin-Flores M, Daugherity EK. Comparison of effects of capromorelin and mirtazapine on appetite in New Zealand White rabbits (Oryctolagus cuniculus). J Am Assoc Lab Anim Sci. 2022;61(5):495-505. PMID 35981857. DOI
11. Di Girolamo N, Maranville RE, Pathak D, Womble W, Hanzlicek A, Sypniewski L, Brandão J. The 4 prokinetic drugs metoclopramide, cisapride, pyridostigmine, and capromorelin do not increase fecal output or food intake in healthy New Zealand rabbits (Oryctolagus cuniculus). J Am Vet Med Assoc. 2025;263(6):755-761. PMID 40179972. DOI
12. Campellone GA, Easley KA, Jenkins JB, Jean SM. Evaluating the safety and efficacy of capromorelin in rhesus macaques (Macaca mulatta). J Am Assoc Lab Anim Sci. 2024;63(3):268-278. PMID 38423529. DOI
13. Ceron-Romero N, Taofeek N, Thomas A, Vroonland E, Sanmartin K, Verghese M, Heinen E, Vizcarra JA. Capromorelin, a ghrelin receptor agonist, increases feed intake and body weight gain in broiler chickens (Gallus gallus domesticus). Poult Sci. 2021;100(8):101204. PMID 34182219. DOI
14. Titel C, Doss G, Mans C. Effects of capromorelin, mirtazapine, and cyproheptadine on food intake in budgerigars (Melopsittacus undulatus). J Avian Med Surg. 2025;39(2):68-74. PMID 40638135. DOI
15. Trumpp K, Burns L, Jacobson C, Divers SJ. Effect of capromorelin on appetite and weight gain of domestic pigeons (Columba livia domestica). J Avian Med Surg. 2025;38(4):197-201. PMID 39772380. DOI

Capromorelin is sold for laboratory research use only. Not for human consumption, nor medical, veterinary, or household uses.