Macimorelin is an orally active ghrelin receptor agonist, a small peptide-like molecule that makes the pituitary gland release a burst of growth hormone (GH). It is the active ingredient in Macrilen, which the FDA approved in December 2017 as a diagnostic test, not a treatment. A single dose is given in a clinic, and blood GH is measured over the next 90 minutes to help confirm adult growth hormone deficiency (AGHD).
The most important fact: macimorelin is approved only as a one-time diagnostic. It has never been approved, or shown in controlled trials, to build muscle, reduce fat or treat any condition. The only treatment-style trial in people was a one-week pilot study in 15 patients with cancer cachexia. In the US, the FDA Orange Book now lists Macrilen as discontinued.
This page summarizes what the FDA label, the European Medicines Agency (EMA) and the clinical trials report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Growth hormone secretagogue receptor (ghrelin receptor) agonist; peptidomimetic |
| Brands | Macrilen (US, NDA 205598, approved December 20, 2017); Ghryvelin (EU, authorised January 11, 2019) |
| Other names | AEZS-130, EP1572 (EP-01572) |
| Route | Oral solution made from granules (60 mg per pouch, 0.5 mg/mL once dissolved) |
| Labeled dose | Single dose of 0.5 mg/kg after fasting at least 8 hours |
| Half-life (label) | Mean terminal half-life 4.1 h after 0.5 mg/kg in healthy adults |
| Metabolism | Mainly CYP3A4 (human liver microsome study) |
| Key safety fact | Prolongs the QTc interval by about 11 msec |
| US status | Prescription diagnostic; not a controlled substance; Orange Book status “discontinued” |
| WADA status | Prohibited at all times (S2.2.4, named as a GH secretagogue) |
What it is
Macimorelin is a small modified peptide (a pseudotripeptide) built from the amino acid 2-aminoisobutyric acid and two D-tryptophan-derived units, with a formylated end group. The label gives the chemical name of the acetate salt as D-tryptophanamide, 2-methylalanyl-N-[(1R)-1-(formylamino)-2-(1H-indol-3-yl)ethyl]-acetate, formula C₂₈H₃₄N₆O₅, molecular weight 534.6 g/mol (Macrilen label). The free base is C₂₆H₃₀N₆O₃, 474.6 g/mol (PubChem CID 9804938). Each 60 mg pouch of macimorelin equals 68 mg of the acetate salt.
It was first reported in people in 2002 under the code EP1572. In two healthy young men, a single oral dose as low as 0.06 mg/kg strongly and reproducibly raised GH (Broglio et al., J Endocrinol Invest 2002). A 2007 dose-escalation study in 36 healthy men confirmed rapid absorption and dose-dependent GH release after oral and intraduodenal dosing (Piccoli et al., JCEM 2007). Aeterna Zentaris later developed it as AEZS-130 for GH testing.
How it raises growth hormone
Macimorelin activates the growth hormone secretagogue receptor (GHSR), the receptor for the gut hormone ghrelin, on cells of the pituitary and hypothalamus (Macrilen label). Cryo-electron microscopy structures published in 2025 show macimorelin and anamorelin sitting in the same receptor pocket, with anamorelin binding more tightly (Wang et al., Acta Pharmacol Sin 2025).
This is the same receptor targeted by other compounds in the library:
| Compound | Type |
|---|---|
| Macimorelin | Peptidomimetic GH secretagogue, approved as a single-dose oral diagnostic |
| Ibutamoren (MK-677) | Oral non-peptide GH secretagogue |
| GHRP-2, GHRP-6, Hexarelin | Synthetic GH-releasing peptides (GHRPs) |
| Ipamorelin | Synthetic GH secretagogue peptide |
By contrast, sermorelin and tesamorelin are instead GHRH analogues, which act on the GHRH receptor; WADA lists both groups under S2.2.4 (WADA 2026 Prohibited List). Because macimorelin works downstream of the hypothalamus and releases GH already stored in the pituitary, the label warns that it can miss GH deficiency early in hypothalamic disease (see below).
Pharmacokinetics
From the label (Macrilen label) and a phase 1 single-ascending-dose trial in 28 healthy adults (Klaus et al., Growth Horm IGF Res 2020):
| Parameter | Value | Source |
|---|---|---|
| Time to peak plasma level | 0.5–1.5 h (AGHD patients, fasted) | Label |
| Time to peak GH | 30–90 min | Label |
| Effect of food | A liquid meal cut peak level by 55% and total exposure (AUC) by 49% | Label |
| Terminal half-life | 4.1 h (0.5 mg/kg, healthy adults) | Label |
| Terminal half-life by dose | 3.51 h at 0.5 and 1.0 mg/kg; 8.29 h at 2.0 mg/kg | Klaus 2020 |
| Metabolism | CYP3A4 is the major enzyme (in vitro) | Label |
Exposure rose less than proportionally with dose, and more drug did not mean more GH. Mean peak GH was 31.9 ng/mL at 0.5 mg/kg and 37.8 ng/mL at 1.0 mg/kg, but about 50% lower (18.4 ng/mL) at 2.0 mg/kg. Short, transient rises in ACTH, cortisol and prolactin were also seen (Klaus et al., 2020).
The fasting rule and the CYP3A4 interaction both matter for the test: anything that lowers macimorelin levels can lower the GH response and produce a false “deficient” result.
Approved medical use
Macrilen is indicated for the diagnosis of adult growth hormone deficiency. Safety and diagnostic performance have not been established in people with a body mass index (BMI) over 40 kg/m² (Macrilen label).
The labeled test works as follows:
- The patient fasts for at least 8 hours. GH therapy is stopped at least one week before, and missing sex, thyroid and adrenal hormones are replaced first.
- A healthcare professional prepares the solution and gives a single dose of 0.5 mg/kg by mouth.
- Blood GH is drawn at 30, 45, 60 and 90 minutes.
- A peak GH under 2.8 ng/mL confirms AGHD.
The EU product, Ghryvelin, is authorised for the same purpose: diagnosis of GH deficiency in adults, as a single 0.5 mg/kg dose (EMA, Ghryvelin EPAR). EMA noted that the test misses some cases but helps confirm a positive diagnosis, and that it avoids the hypoglycemia (low blood sugar) caused by the insulin tolerance test.
US market status
FDA approved Macrilen on December 20, 2017, as a new molecular entity with orphan designation (openFDA Drugs@FDA record). The label was updated in July 2026 to add pediatric study results (FDA supplement approval letter, 2026). The current FDA Orange Book data file lists the product’s marketing status as discontinued (FDA Orange Book data files).
What the research shows
Diagnostic accuracy versus the insulin tolerance test
The insulin tolerance test (ITT), which induces hypoglycemia to provoke GH release, is the traditional reference test. The pivotal phase 3 trial was a multicenter, open-label, randomized crossover study in which each adult took both tests (Garcia et al., JCEM 2018). Participants had a high, intermediate or low likelihood of AGHD, plus matched healthy controls.
Results for the 140 people with both tests, from the label (Macrilen label):
| Group | n | Positive agreement with ITT | Negative agreement with ITT | Overall agreement |
|---|---|---|---|---|
| All participants | 140 | 74% | 94% | 84% |
| High likelihood of AGHD | 38 | 89% | 100% | 89% |
| Intermediate likelihood | 37 | 67% | 86% | 70% |
| Low likelihood | 40 | 33% | 94% | 85% |
| Healthy controls | 25 | 0% (0 of 1) | 96% | 92% |
In plain terms, when the ITT says a person does not have AGHD, macimorelin agrees about 94% of the time. When the ITT says a person does have it, macimorelin agrees only about three times in four at the 2.8 ng/mL cutoff. Other practical findings:
- Failed tests: 1 of 154 macimorelin tests (0.6%) failed for a technical reason, versus 27 of 157 ITTs (17.2%) that failed because adequate hypoglycemia could not be reached.
- Repeatability: 31 of 34 people (91.2%) who took the macimorelin test twice got the same result (label). The published paper reported 97% reproducibility in 33 people.
- Sensitivity and specificity: 87% and 96% at the 2.8 ng/mL cutoff (Garcia et al., 2018).
An earlier multicenter study compared macimorelin with the arginine plus GHRH test in 50 adults with AGHD and 48 controls. It found an optimal cutoff of 2.7 ng/mL, with 82% sensitivity and 92% specificity, and a ROC area under the curve of 0.99 versus 0.94 for arginine plus GHRH (p = 0.29) (Garcia et al., JCEM 2013). Peak GH was inversely related to BMI in controls.
Which cutoff to use
A post hoc analysis of the phase 3 data (limited to BMI under 37 kg/m²) found that age, BMI and sex did not meaningfully change macimorelin’s performance. A higher cutoff of 5.1 ng/mL gave 92% sensitivity and 96% specificity (Garcia et al., Endocr Connect 2021). The FDA label still uses 2.8 ng/mL.
The choice matters in practice. In a 2026 retrospective study of 37 adults at one US center, 15 (40.5%) met AGHD criteria at 2.8 ng/mL versus 20 (54.0%) at 5.1 ng/mL. Most of the reclassified patients had a low pre-test probability and a BMI over 35 kg/m² (Yadav et al., Pituitary 2026). In a 2025 Delphi survey of the Growth Hormone Research Society, adult endocrinologists reached consensus that the macimorelin test can be recommended, with test-specific cutoffs (Arlien-Søborg et al., Pituitary 2025).
Children
Macimorelin is not approved for children. A phase 2 dose-escalation study in 24 children with suspected GH deficiency found no drug-related adverse events and dose-dependent GH release (Csákváry et al., Horm Res Paediatr 2021). The phase 3 crossover study in 102 children, however, failed its primary endpoint: the lower bound of the confidence interval for diagnostic accuracy was 0.66, below the required 0.70. No reliable cutoff could be set to separate children with and without GH deficiency (Macrilen label).
Muscle, body composition and cachexia
There are no controlled trials of macimorelin for muscle mass, strength, fat loss or athletic performance. The only repeated-dose study in patients was a randomized pilot trial in cancer cachexia (weight and muscle loss caused by cancer). Patients took 0.5 or 1.0 mg/kg macimorelin or placebo daily for one week (Herodes et al., J Cachexia Sarcopenia Muscle 2023):
| Pre-set efficacy goal at 1 week | Macimorelin (n = 10) | Placebo (n = 5) | p |
|---|---|---|---|
| Body weight gain of at least 0.8 kg | 2 patients | 0 | 0.92 |
| IGF-1 rise of at least 50 ng/mL | 0 | 0 | — |
| Quality-of-life gain (ASAS) of at least 15% | 4 | 1 | 1.00 |
| Fatigue score gain (FACIT-F) of at least 15% | 3 | 0 | 0.50 |
No differences were statistically significant, and no drug-related adverse events were reported. The authors called the results numerically favorable and said larger, longer studies would be needed. Notably, no patient on macimorelin reached the IGF-1 target after a week of daily dosing.
About “an oral alternative to MK-677.” Macimorelin is sometimes grouped with ibutamoren as an oral GH booster. The shared receptor is real, but the evidence is not comparable. Macimorelin has only been studied as a single-dose test, its half-life is about 4 hours, and in healthy adults a higher dose gave a smaller GH peak, not a larger one. There are no data showing that repeated use raises IGF-1 or lean mass in healthy people.
Side effects and risks
Common side effects
In the phase 3 adult trial, 154 people took one 0.5 mg/kg dose. Reactions seen in at least two people (Macrilen label):
| Adverse reaction | n (of 154) | % |
|---|---|---|
| Dysgeusia (altered taste) | 7 | 4.5 |
| Dizziness | 6 | 3.9 |
| Headache | 6 | 3.9 |
| Fatigue | 6 | 3.9 |
| Nausea | 5 | 3.2 |
| Hunger | 5 | 3.2 |
| Diarrhea | 3 | 1.9 |
| Upper respiratory tract infection | 3 | 1.9 |
| Feeling hot | 2 | 1.3 |
| Excess sweating | 2 | 1.3 |
| Nasopharyngitis | 2 | 1.3 |
| Sinus bradycardia (slow heart rate) | 2 | 1.3 |
The trial reported no serious adverse events with macimorelin (Garcia et al., 2018). The label has no contraindications and no boxed warning.
QT prolongation
The QT interval on an ECG reflects how long the heart takes to reset between beats. Prolonging it can, in rare cases, lead to a dangerous rhythm called torsade de pointes. The label states that macimorelin raises the corrected QT (QTc) by about 11 msec and advises avoiding other QT-prolonging drugs (Macrilen label).
A thorough QT study in 60 healthy adults gave four times the labeled dose (2.0 mg/kg). The maximum mean placebo-adjusted QTcF increase was 9.61 msec (90% CI 7.81–11.41) at 4 hours after dosing, and the upper confidence bound crossed the 10 msec regulatory threshold (Lissy et al., Clin Pharmacol Drug Dev 2021). In the dose-ranging trial, all doses from 0.5 to 2.0 mg/kg prolonged mean QTcF by 10–11 msec, so the effect did not grow with dose (Klaus et al., 2020). In the 2013 validation study, the one drug-related serious adverse event was an asymptomatic QT prolongation (Garcia et al., 2013).
Interactions that distort the test
The label lists these interactions (Macrilen label):
- QT-prolonging drugs (for example some antipsychotics, moxifloxacin, quinidine, amiodarone, sotalol): avoid, because of the added rhythm risk.
- Strong CYP3A4 inducers (for example carbamazepine, phenytoin, rifampin, St. John’s wort, enzalutamide, modafinil): lower macimorelin levels and can cause a false positive result. They should be stopped and washed out first.
- Drugs that change GH release: somatostatin, insulin, glucocorticoids and COX inhibitors such as aspirin or indomethacin affect pituitary GH secretion; clonidine and levodopa can transiently raise GH; atropine, propylthiouracil and GH products can blunt the response.
False negative results
GH deficiency caused by a recent hypothalamic lesion may not show up early, because macimorelin can still release GH stored in the pituitary. Repeat testing may be needed (Macrilen label). The label also notes that GH output normally falls with age, so older adults might need a lower cutoff, and that few people over 65 were studied.
Pregnancy, fertility and long-term data
There are no data in pregnant or breastfeeding women, no animal reproduction or fertility studies, and no long-term rodent cancer studies. Macimorelin was not mutagenic in bacterial or mouse lymphoma cell assays (Macrilen label). Because it was developed for single use, there is no safety information on repeated dosing beyond the one-week cachexia pilot.
Legal status and use outside medicine
- US: a prescription diagnostic (NDA 205598), not listed as a controlled substance in Schedule III (21 CFR 1308.13). The Orange Book lists it as discontinued.
- EU: authorised as Ghryvelin for diagnosing adult GH deficiency and under additional monitoring (EMA, Ghryvelin EPAR).
- Sport: WADA names macimorelin under S2.2.4 (growth hormone secretagogues and their mimetics), prohibited at all times (WADA 2026 Prohibited List). Anti-doping laboratories have developed urine and blood tests for intact macimorelin, with detection limits in the sub-ng/mL range, and identified 12 metabolites in in-vitro and rat studies (Lange et al., Biomed Chromatogr 2021).
Key takeaways
- A diagnostic, not a treatment. Macimorelin is approved in the US and EU only as a single 0.5 mg/kg oral dose to help diagnose adult GH deficiency.
- Same receptor as MK-677 and the GHRPs. It activates the ghrelin receptor, but it is short-acting, with a label half-life of about 4 hours.
- A positive result is reliable, but some cases are missed. It agreed with the insulin tolerance test in 94% of ITT-negative and 74% of ITT-positive adults, without causing hypoglycemia.
- QT prolongation is the main safety signal. It raises QTc by about 10–11 msec, and the label advises avoiding other QT-prolonging drugs.
- No evidence for muscle or performance. The only repeated-dose trial lasted one week in 15 cancer patients and showed no significant effects.
- Prohibited in sport. WADA lists it by name under S2.2.4, and anti-doping tests for it exist.
Sources
- Aeterna Zentaris GmbH. Macrilen (macimorelin) for oral solution, prescribing information. DailyMed, 2026. DailyMed.
- Food and Drug Administration. Drugs@FDA application record, NDA 205598 (Macrilen). openFDA.
- Food and Drug Administration. NDA 205598/S-005 supplement approval letter (pediatric use labeling). July 23, 2026. FDA.
- Food and Drug Administration. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations, data files (products.txt, Macrilen entry). FDA.
- European Medicines Agency. Ghryvelin (previously Macimorelin Aeterna Zentaris): EPAR medicine overview, EMEA/H/C/004660. EMA.
- National Center for Biotechnology Information. Macimorelin, PubChem CID 9804938. PubChem.
- Broglio F, Boutignon F, Benso A, et al. EP1572: a novel peptido-mimetic GH secretagogue with potent and selective GH-releasing activity in man. J Endocrinol Invest. 2002;25(8):RC26–RC28. PubMed.
- Piccoli F, Degen L, MacLean C, et al. Pharmacokinetics and pharmacodynamic effects of an oral ghrelin agonist in healthy subjects. J Clin Endocrinol Metab. 2007;92(5):1814–1820. PubMed.
- Wang RL, Sun J, Liu H, et al. Molecular recognition of two approved drugs Macimorelin and Anamorelin by the growth hormone secretagogue receptor. Acta Pharmacol Sin. 2025;46(11):2998–3008. PubMed.
- Klaus B, Sachse R, Ammer N, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of macimorelin in healthy adults: results of a single-dose, randomized controlled study. Growth Horm IGF Res. 2020;52:101321. PubMed.
- Garcia JM, Biller BMK, Korbonits M, et al. Macimorelin as a diagnostic test for adult GH deficiency. J Clin Endocrinol Metab. 2018;103(8):3083–3093. PubMed.
- Garcia JM, Swerdloff R, Wang C, et al. Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab. 2013;98(6):2422–2429. PubMed.
- Garcia JM, Biller BMK, Korbonits M, et al. Sensitivity and specificity of the macimorelin test for diagnosis of AGHD. Endocr Connect. 2021;10(1):76–83. PubMed.
- Yadav P, Hamrahian AH, Salvatori R. Real-world diagnostic performance of the macimorelin stimulation test in the diagnosis of adult growth hormone deficiency. Pituitary. 2026;29(2):47. PubMed.
- Arlien-Søborg MC, Radovick S, Boguszewski MCS, et al. Consensus and controversies about diagnosing GH deficiency: a Delphi survey by the GH research society. Pituitary. 2025;28(3):57. PubMed.
- Csákváry V, Ammer N, Bagci EB, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of macimorelin in children with suspected growth hormone deficiency: an open-label, group comparison, dose-escalation trial. Horm Res Paediatr. 2021;94(7-8):239–250. PubMed.
- Herodes M, Anderson LJ, Shober S, et al. Pilot clinical trial of macimorelin to assess safety and efficacy in patients with cancer cachexia. J Cachexia Sarcopenia Muscle. 2023;14(2):835–846. PubMed.
- Lissy M, Demmel V, Sachse R, et al. Thorough QT/QTc study evaluating the effect of macimorelin on cardiac safety parameters in healthy participants. Clin Pharmacol Drug Dev. 2021;10(5):494–501. PubMed.
- Lange T, Thomas A, Görgens C, et al. 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. PubMed.
- World Anti-Doping Agency. 2026 Prohibited List. WADA 2026 Prohibited List.
- Code of Federal Regulations. 21 CFR 1308.13, Schedule III. 21 CFR 1308.13.