Ipamorelin

What it is

Ipamorelin is a synthetic pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2) classified as a growth hormone secretagogue. It binds the ghrelin receptor (GHS-R1a) on pituitary somatotrophs. It belongs to the GHRP (growth hormone-releasing peptide) class along with GHRP-2, GHRP-6, and hexarelin.

Ipamorelin was developed by Helsinn Therapeutics in the late 1990s. Helsinn pursued ipamorelin for postoperative ileus (a different indication based on GHRPs’ effects on GI motility), but the development program was discontinued in 2011 after a Phase III trial failed to meet its primary endpoint.

Ipamorelin is not FDA-approved for any use in the United States.

Mechanism of action

Proposed mechanisms come from laboratory, animal, and early-phase pharmacology research. Ipamorelin binds the ghrelin receptor (GHS-R1a), the same receptor activated by endogenous ghrelin. Activation of this receptor has been reported to trigger GH release from pituitary somatotrophs through pathways distinct from GHRH signaling:

• Direct GH release: has been reported to activate intracellular signaling associated with GH secretion independent of GHRH input
• Somatostatin antagonism: GHS-R1a agonists have been reported to reduce somatostatin tone, the primary inhibitor of GH release

The reported half-life is approximately 2 hours.

Research findings

Ipamorelin has more published clinical trial data than many other peptides in this class, owing to its formal pharmaceutical development program:

Pharmacokinetic and pharmacodynamic studies: in Phase I trials in healthy volunteers, ipamorelin was associated with dose-dependent increases in GH.

Postoperative ileus (failed Phase III): ipamorelin was studied for resolution of postoperative ileus based on GHRPs’ effects on GI motility (independent of GH effects). The Phase III trial in 2011 did not show benefit in this indication, and the development program was discontinued.

Well-controlled human trials establishing the effectiveness and safety of ipamorelin for any use are lacking.

Side effects and contraindications

• Human safety has not been established in well-controlled, long-term trials; long-term effects are unknown.
• Because ipamorelin affects the GH/IGF-1 axis, there are theoretical concerns about growth-promoting signaling in people with cancer or a history of cancer, and about effects on blood sugar and insulin sensitivity.
• Products sold outside regulated channels (e.g., “research peptides”) may vary in purity, dose, and sterility.

Theoretical concerns have been raised for: active malignancy, pregnancy and breastfeeding, pituitary disease, severe obesity, active diabetic retinopathy.

What we don’t yet know

Although ipamorelin has more formal clinical research than many other peptides, its long-term effects in adults have not been studied in large trials. Effectiveness and safety over multi-year time horizons have not been established. Whether altering GH-axis signaling in people with normal age-adjusted IGF-1 offers any benefit is unknown and debated.