Macimorelin
An oral ghrelin mimetic used once, as a drink, to test adults for growth hormone deficiency
Macimorelin activates the growth hormone secretagogue (ghrelin) receptor and makes the pituitary release growth hormone; a low response points to deficiency. Approved in the US as Macrilen on December 20, 2017, it is an oral alternative to injected stimulation tests, though Drugs@FDA now lists the product as discontinued.
What is it?
Diagnosing adult growth hormone deficiency usually means a stimulation test: a drug is given to provoke growth hormone release, and a low peak points to deficiency. The reference, the insulin tolerance test, works by inducing hypoglycaemia. Macimorelin, an oral agonist of the ghrelin receptor (GHS-R1a), is drunk once after an overnight fast and growth hormone is measured over the following hours.
The validation came in two steps. A first multicentre study in 50 deficient adults and 48 controls found a peak of 2.36 against 17.71 ng/mL and accuracy comparable with arginine plus GHRH. The phase 3 study then tested it against the insulin tolerance test in the same adults: sensitivity 87% and specificity 96%, with 97% of retests agreeing and no serious adverse events.
The cutoff matters. A post hoc analysis found that a 5.1 ng/mL threshold raised sensitivity to 92% while keeping specificity at 96%, and that age, weight and sex barely changed accuracy. In a 2026 clinic series, though, moving from 2.8 to 5.1 ng/mL labelled 13.5% more patients deficient, and most of the reclassified patients were obese with a low prior likelihood, a reminder that obesity blunts growth hormone responses.
Its main safety point is a modest QT prolongation of about 10 milliseconds, confirmed in a thorough QT study and in higher single doses up to 2.0 mg/kg. The label warns that strong CYP3A4 inducers can cause false positives and recent hypothalamic disease false negatives. In volunteers it raised prolactin and free thyroxine slightly but left the adrenal and gonadal axes untouched.
Children are the open question. A dose-escalation study in 24 children aged 2 to 17 found no drug-related adverse events and growth hormone peaks within an hour, and a review argued it could fill an unmet need, but the US label covers adults only.
It has been tried for something else entirely: a week of daily macimorelin in cancer cachexia was safe and numerically improved weight and quality of life against placebo in a pilot trial, a use that is not approved.
Drugs@FDA lists Macrilen as discontinued while recording an efficacy supplement approved in July 2026, so availability should be checked before planning a test.
Mechanism of Action
Macimorelin mimics ghrelin at its pituitary receptor, provoking a growth hormone pulse that a healthy pituitary can mount and a deficient one cannot.
Ghrelin receptor agonist
Orally active agonist at GHS-R1a (dataset mechanism).
Growth hormone pulse
A single 0.5 mg/kg dose provokes a GH peak within about 30-90 minutes (dataset mechanism; paediatric peaks at 37-53 minutes).
Short-lived
Terminal half-life 4.1 hours after a single oral dose (Macrilen label 12.3).
Published Research
The studies behind macimorelin, read from their PubMed abstracts: the first validation, the phase 3 comparison with the insulin tolerance test and its post hoc cutoff analysis, a clinic series, QT and dose studies, effects on other pituitary hormones, a paediatric dose study and a cachexia pilot. Dosing from the Macrilen label read October 1, 2026.
Against the insulin tolerance test
In adults tested with both, macimorelin had 87% sensitivity and 96% specificity, 97% of retests agreed, and no serious adverse events occurred; a 5.1 ng/mL cutoff raised sensitivity to 92%.
First validation against arginine plus GHRH
In 50 adults with growth hormone deficiency and 48 matched controls, peak GH after oral macimorelin was 2.36 against 17.71 ng/mL; a 2.7 ng/mL cutoff gave 82% sensitivity and 92% specificity, and discrimination matched arginine plus GHRH (AUC 0.99 against 0.94).
Age, weight and sex do not change it
In a post hoc analysis of the phase 3 study, accuracy was essentially unchanged after adjusting for age, BMI or sex (AUC about 0.99 throughout); a 5.1 ng/mL cutoff gave 96% specificity and 92% sensitivity.
Real-world cutoffs and obesity
In 37 adults tested at one centre, 40.5% met the deficiency threshold at 2.8 ng/mL and 54.0% at 5.1 ng/mL; three of five discordant patients had a low pre-test probability and a BMI above 35, and peak GH fell as BMI rose.
Thorough QT study
Macimorelin prolonged QTcF by up to 9.61 milliseconds at 4 hours after dosing, with the upper confidence bound crossing 10 milliseconds at 3 hours; other ECG measures were unchanged.
Higher single doses
In healthy adults, single doses of 0.5 to 2.0 mg/kg were well tolerated, headache was the commonest drug-related event, every dose lengthened QTcF by 10 to 11 milliseconds, and exposure rose less than dose-proportionally.
Other pituitary hormones
In 28 healthy volunteers, single doses of 0.5 and 0.75 mg/kg raised growth hormone sharply and prolactin and free thyroxine slightly, and left copeptin, cortisol, ACTH, LH and FSH unchanged.
Children: a dose-escalation study
In 24 children aged 2 to 17 with suspected deficiency, single doses of 0.25, 0.5 and 1.0 mg/kg caused no drug-related adverse events; exposure rose with dose and growth hormone peaked at 37-53 minutes. Use in children is not on the label.
Cancer cachexia pilot
A week of daily oral macimorelin was safe in patients with cancer cachexia and numerically improved body weight and quality of life against placebo; this use is not approved.
Testing children
A review argued that macimorelin, approved for adults, could meet an unmet need in diagnosing childhood-onset growth hormone deficiency, given the drawbacks of current provocation tests.
Dosing Data
A single dose by label after an 8-hour fast, with interfering drugs stopped beforehand.
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Side Effects & Contraindications
Reported Side Effects
From the Macrilen label (version 3).
Contraindications & Cautions
From the label.
Legal Status
Approved in the US; product listed as discontinued.
Frequently Asked Questions
?How does the test work?
After an 8-hour fast the patient drinks 0.5 mg/kg; growth hormone is measured afterwards, and a low peak suggests deficiency.
?Is it safer than the insulin tolerance test?
It avoids deliberate hypoglycaemia; its own main risk in the studies was a QT increase of about 10 milliseconds.
?Is it the same as anamorelin?
No. Both act on the ghrelin receptor, but anamorelin is a different molecule developed for cancer cachexia.
?Which cutoff is used?
Two thresholds appear in the studies: 2.8 ng/mL and 5.1 ng/mL. The higher one raised sensitivity to 92% with 96% specificity in a post hoc analysis, but in obese patients it may over-call deficiency.
?Does obesity affect the result?
Yes: in a clinic series, peak growth hormone fell as BMI rose, and most patients reclassified by the higher cutoff had a BMI above 35.
?Can children be tested with it?
Not under the US label. A dose study in 24 children found no drug-related adverse events, but paediatric use is not approved.
?Does it affect other hormones?
In volunteers it raised prolactin and free thyroxine slightly and left cortisol, ACTH, LH, FSH and copeptin unchanged.
?Is it still available?
Drugs@FDA lists Macrilen as discontinued, though it recorded an efficacy supplement in July 2026; check availability first.
References
- [fda-pi] Macrilen (macimorelin) for oral suspension US prescribing information (DailyMed version 3, effective February 18, 2026); read October 1, 2026.
- [clinical-trial] Garcia JM, et al. "Macimorelin as a Diagnostic Test for Adult GH Deficiency." J Clin Endocrinol Metab, 2018;103(8):3083-3093. PMID: 29860473.
- [clinical-trial] Lissy M, 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. PMID: 32961034.
- [clinical-trial] Klaus B, 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. PMID: 32325373.
- [clinical-trial] Herodes M, 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. PMID: 36860137.
- [review] Henry RK. "Macimorelin Acetate for the Diagnosis of Childhood-onset Growth Hormone Deficiency." touchREV Endocrinol, 2022;18(2):84-85. PMID: 36694890.
- [clinical-trial] Garcia JM, 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):2422-9. PMID: 23559086.
- [pubmed] Garcia JM, et al. "Sensitivity and specificity of the macimorelin test for diagnosis of AGHD." Endocr Connect, 2021;10(1):76-83. PMID: 33320108.
- [clinical-trial] Csákváry V, 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. PMID: 34438400.
- [pubmed] Urwyler SA, et al. "Effects of oral macimorelin on copeptin and anterior pituitary hormones in healthy volunteers." Pituitary, 2021;24(4):555-563. PMID: 33615399.
- [pubmed] Yadav P, et al. "Real-world diagnostic performance of the macimorelin stimulation test in the diagnosis of adult growth hormone deficiency." Pituitary, 2026;29(2). PMID: 41793495.
Sources & Citations
Dosing and warnings from the Macrilen label (DailyMed version 3, effective February 18, 2026, read October 1, 2026); approval and status from Drugs@FDA; studies from PubMed abstracts.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.