Macimorelin is not a daily peptide, supplement, or "GH booster." It is a one-time oral test a clinician uses to find out whether the pituitary gland can release enough growth hormone. After drinking the prepared solution on an empty stomach, blood is drawn a few times over 90 minutes to measure the growth-hormone response. It is FDA-approved specifically for diagnosing adult growth hormone deficiency — and should never be marketed for bodybuilding, anti-aging, or fat loss.
Macimorelin is an orally active growth-hormone-secretagogue-receptor (GHS-R1a / ghrelin-receptor) agonist. The labeled test is a single 0.5 mg/kg oral dose after ≥8 hours fasting, with serum GH measured at 30, 45, 60 and 90 minutes; a peak GH below 2.8 ng/mL supports adult GHD. It is valued as a simpler, oral alternative to the insulin tolerance test, which requires induced hypoglycemia. In the pivotal trial, 99% of macimorelin tests were evaluable versus 82% of ITTs. Key gating: QTc prolongation, strong CYP3A4 inducers, and GH-axis medication washout.
Macimorelin (Aib-D-Trp-D-gTrp-CHO; C₂₆H₃₀N₆O₃ free base, MW ≈ 474.55 Da, CAS 381231-18-1, PubChem CID 9804938; formerly AEZS-130 / JMV-1843) is a synthetic peptidomimetic ghrelin mimetic that binds GHS-R1a in the pituitary and hypothalamus with affinity similar to ghrelin, driving a dose-dependent GH pulse peaking within an hour. The 2013 validation found an optimal GH cut point of 2.7 ng/mL (82% sensitivity, 92% specificity), comparable to GHRH+arginine; the 2018 pivotal crossover against ITT reported 95% negative and 74% positive agreement with 97% reproducibility. Oral bioavailability with a ~4-hour half-life and CYP3A4 metabolism distinguishes it from injectable secretagogues.
Macimorelin is one of the cleanest entries in this atlas precisely because it is not an open-ended peptide: it is an FDA-approved, label-defined diagnostic with a fixed dose, route, preparation, sampling schedule, interpretation cutoff, and safety set. It belongs in an endocrine-testing context — a single oral probe of pituitary GH reserve — not in any performance, longevity, or daily-secretagogue protocol.
Macimorelin works by impersonating ghrelin. It is a small, orally stable peptidomimetic that switches on the same receptor the stomach's hunger hormone uses to provoke growth-hormone release — turning a drinkable dose into a timed, measurable GH surge that reveals whether the pituitary still has reserve to draw on.
| Property | Macimorelin (GHS-R1a) | GHRH analogs (GHRH-R) |
|---|---|---|
| Receptor | Ghrelin receptor (GHS-R1a) | GHRH receptor |
| Coupling | Gq/11 → PLC → Ca²⁺/PKC | Gs → cAMP → PKA |
| Route | Oral | SC / IV |
| Atlas role | Approved adult-GHD diagnostic | Diagnostic + therapeutic (e.g., sermorelin, tesamorelin) |
| Example | Macimorelin; ipamorelin, MK-677 (therapeutic GHS) | Sermorelin, CJC-1295, tesamorelin |
| Parameter | Macimorelin | Basis |
|---|---|---|
| Receptor / coupling | GHS-R1a · Gq/11 → PLC | Ghrelin-mimetic pharmacology |
| Half-life | ≈ 4.1 h; CYP3A4 metabolism | PK reference |
| GH Tmax | 30–90 min | Label PK/PD |
| Food effect | Cmax −55%, AUC −49% (liquid meal) | Fasting requirement |
| Approved dose | 0.5 mg/kg oral, single, fasting ≥8 h | FDA label |
| Cutoff | Peak GH < 2.8 ng/mL = AGHD | FDA label |
Unlike most peptides in this atlas, macimorelin has a single, fully specified, FDA-labeled protocol — a dose, a fasting rule, a preparation method, a sampling schedule, and an interpretation cutoff. The panels below separate the approved adult protocol from preparation mechanics, interpretation, the not-yet-approved pediatric research, and the washout rules that protect test integrity. This is a one-time diagnostic, never a daily or repeated dosing regimen.
0.5 mg/kg orally, once, after fasting ≥ 8 hours. The labeled single-dose protocol.| Step | Action | Note |
|---|---|---|
| Prep day | Confirm washouts; fast ≥ 8 h | GH products off ≥ 1 week |
| T = 0 | Drink reconstituted solution | Use within 30 min of prep |
| T = 30 min | Draw serum GH | Early peak window |
| T = 45 min | Draw serum GH | — |
| T = 60 min | Draw serum GH | — |
| T = 90 min | Draw serum GH | Final sample; take max of four |
| Body weight | Dose | Solution volume | Pouches (60 mg) |
|---|---|---|---|
| 60 kg | 30 mg | 60 mL | 1 |
| 70 kg | 35 mg | 70 mL | 1 |
| 90 kg | 45 mg | 90 mL | 1 |
| 120 kg | 60 mg | 120 mL | 1 |
| 130 kg | 65 mg | 130 mL | 2 (> 120 kg) |
| Field | Value | Source |
|---|---|---|
| Storage | Refrigerated 2–8 °C | Label |
| Reconstitution | 60 mg in 120 mL water | Label |
| Final concentration | 0.5 mg/mL | Label |
| Use window | Within 30 minutes | Label |
| Unused solution | Discard | Label |
| Cutoff | Sensitivity | Specificity | Note |
|---|---|---|---|
| 2.8 ng/mL (label) | 87% | 96% | Prespecified maci cutoff |
| 5.1 ng/mL (post-hoc) | 92% | 96% | Both-test harmonized cutoff |
| 2.7 ng/mL (2013) | 82% | 92% | Early validation |
| Result | Meaning | Action |
|---|---|---|
| Peak GH < 2.8 ng/mL | Supports adult GHD | Correlate with context; consider GH therapy workup |
| Peak GH ≥ 2.8 ng/mL | GHD not supported | Consider false-negative if recent hypothalamic disease |
| Borderline + high pre-test prob. | Indeterminate | Repeat testing may be warranted |
| Test technically failed | Non-evaluable | Repeat; maci failure rate is low |
| Cohort | Dose | Mean GH Tmax | Status |
|---|---|---|---|
| C1 | 0.25 mg/kg | ~52 min | Research |
| C2 | 0.5 mg/kg | ~38 min | Research |
| C3 | 1.0 mg/kg | ~38 min | Most discriminating |
| Effect | Examples | Action |
|---|---|---|
| Directly affect GH secretion | Somatostatin, insulin, glucocorticoids, aspirin, indomethacin | Review / time around test |
| Transiently elevate GH | Clonidine, levodopa, insulin | Avoid acutely pre-test |
| Blunt GH response | Atropine, propylthiouracil, GH products | Washout (GH ≥ 1 week) |
| Lower maci levels (CYP3A4↑) | Carbamazepine, phenytoin, rifampin, St. John's wort, modafinil | Washout — false-positive risk |
For clinician/educational reference only — computes the FDA-labeled single diagnostic preparation (0.5 mg/kg at 0.5 mg/mL). Not medical advice and not a daily/therapeutic dose. The 0.25 / 1.0 mg/kg and 1.0 mg/mL options reflect pediatric research parameters and are not label-approved. Confirm fasting and medication washout before testing.
For a diagnostic agent, "combinations" are mostly things to remove, not add. Macimorelin has no performance or longevity stack — co-administered GH secretagogues, QT-prolonging drugs, and strong CYP3A4 inducers all corrupt the result or add risk. The one legitimate "combination" is the opposite of stacking: replacing other pituitary deficiencies before the test so the GH axis can be read cleanly.
| Agent | Effect on test | Action |
|---|---|---|
| Somatropin (GH) | Blunts GH response | Stop ≥ 1 week prior |
| Class | Example | Action |
|---|---|---|
| GHRH analog | Sermorelin, CJC-1295 | Not appropriate around test |
| Ghrelin agonist / GHS | Ipamorelin, MK-677 | Confounder — exclude |
| Category | Examples | Action |
|---|---|---|
| Class IA / III antiarrhythmics | Quinidine, procainamide, amiodarone, sotalol | Avoid / washout |
| Antipsychotics | Haloperidol, thioridazine, ziprasidone, chlorpromazine | Avoid / washout |
| Antibiotic | Moxifloxacin | Avoid / washout |
| Example | Mechanism | Action |
|---|---|---|
| Rifampin, carbamazepine, phenytoin | ↑ CYP3A4 → ↓ maci levels | Washout before test |
| St. John's wort, modafinil, enzalutamide | ↑ CYP3A4 | Washout before test |
| Effect | Examples | Action |
|---|---|---|
| Suppress / blunt | Somatostatin, glucocorticoids, atropine | Review timing |
| Transiently elevate | Clonidine, levodopa, insulin | Avoid acutely pre-test |
| Axis | Why replace first | Grade |
|---|---|---|
| Thyroid (T4/TSH) | Thyroid status affects GH axis | A |
| Adrenal (cortisol) | Glucocorticoid deficiency confounds | A |
| Gonadal (T/E₂) | Sex steroids modulate GH | A |
| Test | Relationship | Grade |
|---|---|---|
| ITT | Reference comparator | A |
| Glucagon / GHRH-arg | Alternative choices | A/B |
| Use | Status | Reason |
|---|---|---|
| "Boost GH" / cycle | Blocked | Not label-supported |
| Stack with peptides | Blocked | Confounds GH testing |
As a single oral diagnostic dose, macimorelin is generally well tolerated — adverse events in the trials were mostly mild and transient, with no serious events reported for macimorelin. The clinically important issues are cardiac (QTc prolongation), pharmacokinetic (CYP3A4-inducer false positives), interpretive (recent hypothalamic disease false negatives), and population limits (BMI > 40, pediatric, geriatric, pregnancy).
| Reaction | Rate | Reaction | Rate |
|---|---|---|---|
| Dysgeusia | 4.5% | Nausea | 3.2% |
| Dizziness | 3.9% | Hunger | 3.2% |
| Headache | 3.9% | Diarrhea / URTI | 1.9% |
| Fatigue | 3.9% | Feeling hot / hyperhidrosis | 1.3% |
| Nasopharyngitis | 1.3% | Sinus bradycardia | 1.3% |
| Marker | Purpose | Note |
|---|---|---|
| Serum GH (30/45/60/90 min) | Primary test output | Take maximum value |
| IGF-1 | Pre-test probability / axis context | Not diagnostic alone |
| TSH / free T4 | Thyroid status | Replace deficiency first |
| AM cortisol / ACTH | Adrenal axis | Address glucocorticoid deficiency |
| LH/FSH · testosterone/estradiol | Gonadal axis | Affects interpretation |
| QT / ECG review | Cardiac safety screen | If QT risk or interacting meds |
| BMI | Appropriateness | Limitation > 40 |
Review QT/ECG and interacting medications; confirm CYP3A4-inducer, QT-drug, and GH washout; ensure ≥8-hour fast. Replace thyroid, glucocorticoid, and sex-hormone deficiencies. Record BMI (limitation >40). Consider IGF-1 and the broader pituitary panel for pre-test probability.
Single oral dose; draw GH at 30/45/60/90 min. Observe for transient dysgeusia, dizziness, headache, nausea. QT awareness in at-risk patients. No serious adverse events were reported for macimorelin in the pivotal trial.
Take the maximum of four GH values against the 2.8 ng/mL cutoff in clinical context. Consider false-negative risk in recent hypothalamic disease and false-positive risk with CYP3A4 inducers. Repeat testing may be warranted in borderline or discordant cases.
| Condition | Concern | Severity · grade |
|---|---|---|
| Concomitant QT-prolonging drugs | Additive torsade risk | High |
| Congenital long-QT / significant QT risk | Arrhythmia potential | High |
| Strong CYP3A4 inducers | False-positive result | High (test validity) |
| Recent-onset hypothalamic disease | False-negative result | Moderate–High |
| BMI > 40 kg/m² | Performance not established | Caution |
| Pediatric use | Safety/efficacy not established (label) | Investigational |
| Age ≥ 65 / > 70 | Limited data; GH declines with age | Caution |
| Pregnancy | No adequate human data (single-dose exposure) | Caution |
| Lactation | No milk/exposure data | Caution |
| Unreplaced pituitary deficiencies | Replace thyroid/adrenal/gonadal first | Moderate |
| Active GH therapy | Blunts response; stop ≥ 1 week | Moderate |
| Drugs transiently elevating GH (clonidine, levodopa) | Distort peak | Caution |
| Glucose intolerance / diabetes context | Affects GH-axis interpretation | Monitor |
| Non-evaluable / failed test | Technical repeat needed | Repeat |
| At-home / unsupervised use | Safety + interpretation risk | Avoid |
| Use as daily/therapeutic secretagogue | Not label-supported | Avoid |
| QT-prolonging antibiotics (e.g., moxifloxacin) | Additive QT effect | Avoid / washout |
| Antipsychotics (haloperidol, ziprasidone) | QT prolongation | Avoid / washout |
| Electrolyte disturbance (hypoK/hypoMg) | Amplifies QT risk | Correct first |
| Mitotane / enzalutamide / bosentan (CYP3A4↑) | Lower maci levels → false positive | Washout |
| Cushingoid / high-glucocorticoid state | Blunts GH response | Caution |
Macimorelin is among the best-evidenced agents in this atlas for its specific use: a validation study, an FDA-pivotal randomized crossover against the gold-standard insulin tolerance test, documented reproducibility, and guideline/HTA recognition. The pediatric program is the honest counterweight — a phase-2 success but a phase-3 trial that missed its primary endpoint, keeping pediatric use investigational.
Multicenter, open-label, randomized two-way crossover validating single-dose oral macimorelin against the insulin tolerance test in adults across low/intermediate/high GHD likelihood plus matched controls. At the 2.8/5.1 ng/mL cutoffs, negative agreement was 95.4% and positive agreement 74.3%; reproducibility ~97%; no serious adverse events for macimorelin.
Open-label study comparing oral macimorelin with GHRH+arginine in AGHD patients and controls; ROC analysis gave an optimal GH cut point of 2.7 ng/mL (82% sensitivity, 92% specificity), with discrimination comparable to GHRH+arginine and a single asymptomatic QT prolongation as the only drug-related serious event.
Approved label defining the 0.5 mg/kg fasting oral protocol, 30/45/60/90-min GH sampling, the 2.8 ng/mL cutoff, reconstitution to 0.5 mg/mL, QTc warning, CYP3A4-inducer and GH-axis interactions, the BMI > 40 limitation, and the pediatric/geriatric/pregnancy data gaps.
Open-label dose-escalation trial (n=24, ages ~4–15) testing 0.25, 0.5 and 1.0 mg/kg with good safety/tolerability and dose-proportional PK; GH rose after dosing with the highest dose most discriminating — supporting a 1.0 mg/kg design for the pediatric phase-3 trial.
Phase-3 trial (n=102, ages 3–17) reporting potent GH release and confirmed pediatric safety, but the primary endpoint was not met per protocol; the adjudicated "optimal" cutoff (~25.6 ng/mL) sat far above standard pediatric thresholds, with surprising discordances under further analysis — keeping pediatric use investigational.
Health-technology review summarizing the pivotal trial and a post-hoc analysis showing test performance (AUROC ≈ 0.99) was not meaningfully affected by age, BMI, or sex, with sensitivity ~88% and specificity ~97% at the 2.8 ng/mL cutoff.
Endocrine Connections review placing macimorelin among GH-stimulation tests: attractive for being oral, reproducible, safe, and comparable in accuracy to ITT and GHRH+arginine, while noting barriers of cost, access, drug interactions, and limited data in children and patients > 70.
Clinical practice guidance emphasizing that adult GHD diagnosis requires biochemical confirmation with a GH-stimulation test in the right clinical context (structural pituitary disease, surgery/radiation, multiple pituitary deficiencies, TBI), not symptoms alone — the framework macimorelin testing serves.
Chemical records for the free base (C₂₆H₃₀N₆O₃, MW 474.55, CAS 381231-18-1, CID 9804938) and the acetate salt (C₂₈H₃₄N₆O₅, MW 534.6), confirming the Aib-D-Trp-D-gTrp-CHO pseudotripeptide, ghrelin-receptor agonist class, ~4.1 h half-life, and CYP3A4 metabolism.
The ITT remains the reference GH-stimulation test, with sensitivity ~96% and specificity ~92%, but it deliberately induces hypoglycemia and is contraindicated in coronary artery disease, seizure disorders, and the elderly. These limitations are precisely what an oral alternative like macimorelin addresses, and why test-failure rates differ so sharply between the two.
GHS-R1a is a class-A GPCR signaling through Gq/11–phospholipase C–IP₃/DAG–Ca²⁺/PKC with notable constitutive activity. Macimorelin engages this ghrelin arm — mechanistically distinct from the GHRH-receptor (Gs/cAMP) arm used by sermorelin-type analogs — which is why the two secretagogue classes can be used to interrogate GH reserve from different angles.
The label's clinical-pharmacology data show a liquid meal reduced macimorelin Cmax by 55% and AUC by 49%, with GH peaking 30–90 minutes post-dose. This exposure sensitivity is the quantitative basis for the ≥8-hour fasting rule and a reminder that protocol deviations directly threaten test validity.
Reproducibility is a core attribute of a diagnostic: repeat macimorelin testing agreed with the first test in ~97% of retested subjects (and ~91% in the label's 34-subject repeatability set), supporting confidence that a single oral protocol yields stable results across occasions.
Where the ITT is unsuitable, the glucagon stimulation test is an option but is long, nausea-prone, and BMI/cutoff-sensitive. Glucagon serves as an ITT alternative with these practical drawbacks, while GHRH+arginine is historically accurate but constrained by limited GHRH availability in markets such as the US — the access gap macimorelin was designed to fill.
Developed by Aeterna Zentaris (as AEZS-130 / JMV-1843), macimorelin received FDA approval in December 2017. It is marketed as Macrilen in the US, South Korea, and Israel and as Ghryvelin in the European Economic Area, with the developer now operating as COSCIENS Biopharma — useful provenance for sourcing and label-version tracking.
A common cataloguing error is conflating the salt and free base. The acetate (C₂₈H₃₄N₆O₅, ~534.6, CAS 945212-59-9) is the formulated salt — 60 mg base ≈ 68 mg acetate per pouch, while the free base (C₂₆H₃₀N₆O₃, 474.55) is the active moiety the dose is expressed in. The page's identity card states both explicitly.
Macimorelin's value proposition is entirely comparative: it is the oral, low-burden alternative to a panel of older, more cumbersome GH-stimulation tests. Against the gold-standard insulin tolerance test it trades a little positive agreement for a large gain in safety and feasibility. Within the secretagogue family, it is the diagnostic GHS — distinct from the therapeutic GHRH analogs and ghrelin agonists.
| Test / agent | Type | Strengths | Weaknesses | Route / burden | Status |
|---|---|---|---|---|---|
| Macimorelin | Oral GHS-R1a agonist (Dx) | Oral, simple, reproducible; avoids hypoglycemia | QT/CYP3A4 gating; BMI > 40 limit | Oral · low | FDA-approved (adult GHD) |
| Insulin tolerance test (ITT) | Hypoglycemia provocation | Reference standard (sens 96% / spec 92%) | Induced hypoglycemia; contraindications; failures | IV · high | Reference standard |
| Glucagon stimulation test | Glucagon provocation | Useful when ITT unsuitable | Long, nausea, BMI/cutoff complexity | IM · moderate–high | Widely used |
| GHRH + arginine | GHRH-R + arginine | Historically accurate alternative | GHRH availability limited (US); IV | IV · moderate | Limited availability |
| Arginine alone / L-dopa | Amino-acid / dopaminergic | Simple | Lower discrimination | IV/oral · moderate | Adjunctive |
| Ipamorelin / MK-677 | Therapeutic GHS (ghrelin arm) | GH-axis stimulation (research/therapeutic) | Not diagnostic; not approved for Dx | SC / oral | Not FDA-approved (Dx) |
| Sermorelin / tesamorelin | GHRH analogs (GHRH arm) | Therapeutic GH-axis (tesamorelin approved) | Different receptor arm; not the maci use | SC | Tesamorelin FDA-approved |
Evidence grades reflect the strength of support for the specific claim cited, not the prestige of the journal. Macimorelin's FDA label, pivotal crossover trial, and earlier validation are its firmest evidence; guideline, HTA, and review sources anchor the diagnostic framework; the pediatric trials and database/PK records define the boundaries of its use.