Macimorelin

Macimorelin (Macrilen) is a synthetic peptidomimetic agonist of the growth hormone secretagogue receptor 1a (GHSR1a, the ghrelin receptor). It is classified as a peptidomimetic rather than a peptide: its molecular structure mimics the peptide ghrelin but is not itself a conventional peptide (free-base molecular formula C26H30N6O3; molecular weight 474.6 g/mol). FDA-approved in December 2017 as a single-oral-dose diagnostic test for adult growth hormone deficiency (AGHD). It replaced the insulin tolerance test (ITT) as a simpler, safer alternative.

Macimorelin is an orally available, non-peptide agonist at the GHSR1a receptor. It stimulates GH secretion from the anterior pituitary after oral administration, allowing GH measurement in serial blood samples over 90 minutes. Compared to the insulin tolerance test (ITT), macimorelin avoids the risk of severe hypoglycemia.

Approved labeled regimen

The label summary below is product-, indication-, and jurisdiction-specific; consult the full current label and a licensed clinician/pharmacist.

• 0.5 mg/kg (of the macimorelin active moiety) administered as a single oral solution.

• Reconstituted granules in water; administered by a healthcare professional.

• GH measured in 4 blood samples over 90 minutes after dosing.

• Not for BMI >40 kg/m2 (insufficient validation).

Studied regimens (not recommendations)

Investigational use for cachexia has been studied (phase 2); no approved therapeutic indication.

What is not established

The label establishes a single diagnostic exposure, not a treatment regimen. No therapeutic regimen is established or recommended for cachexia or GH-deficiency treatment.

Established label risks

• Most common adverse reactions: dysgeusia (metallic taste), dizziness, headache, nausea, fatigue, diarrhea.

• QT prolongation: macimorelin causes an increase in the QTc interval of ~9.6 ms at the diagnostic dose. Avoid in patients with congenital long QT syndromes or in combination with other drugs that prolong the QT interval. Torsades de pointes has been reported.

• Hypersensitivity reactions including anaphylaxis.

• False-positive results: strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) reduce macimorelin exposure and GH stimulation, potentially causing a false-positive diagnosis of GHD. Discontinue strong CYP3A4 inducers and observe a washout period sufficient to allow recovery of enzyme activity before testing.

• False-negative results: recent onset of hypothalamic disease (within 12 months) can cause a falsely normal GH response. Consider this in the diagnostic assessment.

• Not recommended in patients with severe hepatic impairment or renal impairment (eGFR <30 mL/min/1.73 m²).

Human-study signals

No serious safety signals in the diagnostic context. Therapeutic doses for cachexia studied but not approved.

Unknowns and product-quality risks

Products sold as "research peptide macimorelin" are likely misrepresented; the material is a small-molecule peptidomimetic.

• Strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin, St. John's wort): discontinue and allow adequate washout before testing to avoid false-positive GHD diagnosis (reduced GH response).

• Drugs affecting GH secretion (somatostatin, somatropin, glucocorticoids, pegvisomant) may interfere with test results.

• Concomitant QT-prolonging drugs increase risk of arrhythmia.

• Growth hormone replacement therapy: discontinue at least one week before testing.

• Pregnancy: no adequate human data.

• Pediatric use not established.

• FDA and EMA approved for diagnostic use only.

• WADA: S2.2.4 — growth hormone secretagogues (GHS) and their releasing factors. Macimorelin is explicitly named and is prohibited at all times. This page does not predict TUE eligibility or outcome; athletes need a case-specific determination under the current anti-doping rules before use.

• No US federal CSA scheduling was identified as of 2026-08-06; state law and other jurisdictions were not assessed.

• Utility in patients with BMI >40.

• Head-to-head comparison with newer GH stimulation tests.

• Long-term safety at therapeutic doses for cachexia not adequately studied.

• Databases and registries: FDA label, PubMed, ClinicalTrials.gov, DrugBank

• Search terms: "macimorelin", "Macrilen", "AEZS-130", "ghrelin agonist"

• Last searched: 2026-08-06

• Inclusion emphasis: FDA label, pivotal phase 3 trial

1. FDA. Macrilen (macimorelin) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205598s000lbl.pdf

2. EMA. Ghryvelin (macimorelin) EPAR. https://www.ema.europa.eu/en/medicines/human/EPAR/ghryvelin

3. Garcia JM, et al. Phase 3 trial of macimorelin for AGHD diagnosis. J Clin Endocrinol Metab. 2018;103(7):2565-2573.

4. PubChem. Macimorelin free base (CID 9804938). https://pubchem.ncbi.nlm.nih.gov/compound/9804938

5. DrugBank. Macimorelin (DB13074). https://go.drugbank.com/drugs/DB13074

6. World Anti-Doping Agency. 2026 Prohibited List, S2.2.4. https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf

7. PubChem PUG REST. Macimorelin acetate (CID 71526737), molecular formula and weight record. https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/71526737/property/MolecularFormula,MolecularWeight/JSON

8. FDA. Macrilen product-quality review (macimorelin acetate identity and CAS). https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/205598Orig1s000ChemR.pdf