Macimorelin
FDA-approved oral ghrelin receptor agonist (Macrilen) — the only oral diagnostic test for adult GH deficiency. Growing biohacking interest as a convenient oral GH secretagogue alternative to injectables.
🔬 Mechanism of Action
Macimorelin (AEZS-130) is a peptidomimetic ghrelin receptor agonist — an orally active synthetic compound that mimics ghrelin's binding at growth hormone secretagogue receptor type 1a (GHS-R1a) on pituitary somatotroph cells. Unlike ghrelin itself (28 amino acids), macimorelin is a small molecule that survives the GI tract and achieves ~80% oral bioavailability.
Upon absorption, macimorelin activates GHS-R1a to stimulate GH release from pituitary somatotrophs. Peak GH response occurs approximately 45-60 minutes post-dose. FDA-approved (Macrilen, 2017) as a diagnostic agent for adult GH deficiency (AGHD) — replacing invasive ITT and GHRH+arginine tests.
The pharmacological mechanism is identical to injectable ghrelin/GHRP analogs (Ipamorelin, GHRP-6, hexarelin) but delivered orally. This has attracted biohacking interest as an injection-free route to GH secretagogue activity. The trade-off vs MK-677 (the other oral GHS): macimorelin produces a single acute GH pulse (~4-6h half-life) while MK-677 produces sustained 24-hour GH/IGF-1 elevation.
Source: FDA Label (Macrilen), PMID: 30011461
📜Background & History
Macimorelin (AEZS-130) is an orally active peptidomimetic ghrelin agonist developed by Aeterna Zentaris, FDA-approved in 2017 as Macrilen for the diagnosis of adult growth hormone deficiency (AGHD). It is the only oral GH stimulation test approved in the US, replacing older tests (insulin tolerance test, arginine + GHRH) that required IV administration and medical supervision for hypoglycemia risk. In biohacking circles, macimorelin's oral activity and ghrelin receptor selectivity (similar to MK-677 but with different pharmacokinetics) have attracted interest as an alternative or complement to MK-677 for GH optimization. One key difference: macimorelin has a ~4-6 hour half-life vs MK-677's 5-hour half-life, but MK-677 causes sustained IGF-1 elevation for 24 hours while macimorelin causes a discrete diagnostic peak.
🎯 Research Use Cases
- ✓Adult growth hormone deficiency diagnosis (FDA-approved, Macrilen)
- ✓GH secretagogue research: oral GH pulse stimulation
- ✓Assessment of pituitary GH reserve without IV procedures
- ✓Biohacking GH optimization as injection-free alternative to GHRP stack
💉 Dosing Protocol
| Typical Dose | 0.5 mg/kg (diagnostic) or 1-2 mg/day (research) |
| Frequency | 1× daily (oral) |
| Half-Life | ~4-6 hours |
⚠️Safety & Considerations
FDA-approved (Macrilen) for diagnostic use only. For diagnostic testing: administer as a single 0.5 mg/kg oral dose after 8-hour fast. Contains lactose — contraindicated in severe lactose intolerance. CYP3A4 drug interactions: avoid strong CYP3A4 inhibitors (ketoconazole) or inducers (rifampin) within 2 hours. QT prolongation risk — avoid with QT-prolonging drugs. Monitor for hypoglycemia.
⚡Interactions & Contraindications
Contains lactose — avoid in lactose intolerance. Moderate CYP3A4 inhibitors increase macimorelin exposure — avoid ketoconazole, erythromycin, grapefruit juice within 2 hours. Must fast for 8 hours before the diagnostic dose. Fatty meal blunts GH peak by 50%. Somatostatin analogs (octreotide) antagonize the GH response. Clonidine and other GH-stimulating drugs affect test interpretation.
🔗Synergies & Common Stacks
Both are ghrelin receptor agonists — combining would risk receptor saturation without additive benefit. Use one or the other, not both simultaneously.
If using macimorelin as a GHRP, pairing with a GHRH analog (Mod GRF) follows the same synergistic mechanism as GHRH + GHRP stacks — macimorelin provides the ghrelin-pathway pulse, CJC provides amplitude.
