Ipamorelin research: what the published studies show

Development and Selectivity

A 1998 paper describes ipamorelin as a pentapeptide identified within a series of compounds lacking the central Ala-Trp dipeptide of GHRP-1.^[1] In primary rat pituitary cells it released GH with potency and efficacy similar to GHRP-6, at an EC50 of 1.3 nmol/l against GHRP-6's 2.2 nmol/l.^[1] Pharmacological profiling with GHRP and GHRH antagonists placed its action at the same receptor as GHRP-6 rather than the GHRH receptor.^[1]

In pentobarbital-anaesthetised rats its ED50 was 80 nmol/kg with a maximum of 1,545 ng GH/ml, against GHRP-6's 115 nmol/kg and 1,167 ng/ml.^[1] In conscious swine the ED50 was 2.3 nmol/kg with a maximum of 65 ng GH/ml plasma, close to GHRP-6's 3.9 nmol/kg and 74 ng/ml.^[1] GHRP-2 showed higher potency but lower efficacy in swine.^[1]

Specificity was tested in swine.^[1] None of the secretagogues affected FSH, LH, prolactin or TSH.^[1] Both GHRP-6 and GHRP-2 raised plasma ACTH and cortisol.^[1] Ipamorelin did not release ACTH or cortisol at levels significantly different from those observed following GHRH stimulation.^[1] That comparison is against GHRH rather than against no treatment, and the distinction is the source's own wording.^[1] The authors call the finding surprising, and report it held at doses more than a hundred-fold above the GH-releasing ED50.^[1]

Longitudinal Bone Growth in Rats

A 1999 study injected adult female rats subcutaneously three times daily for 15 days, at 0, 18, 90 and 450 micrograms per day.^[2] Longitudinal growth rate was measured in the proximal tibia metaphysis using intravital tetracycline labeling on days 0, 6 and 13.^[2] Growth rate rose dose-dependently from 42 micrometres per day in controls.^[2] There was also a pronounced dose-dependent effect on body weight gain.^[2]

The treatment did not affect total IGF-1 levels, IGF binding proteins, or serum markers of bone formation and resorption.^[2] The number of tartrate-resistant acid phosphatase-positive multinuclear cells in the tibial metaphysis did not change significantly.^[2] Those nulls sit in the same study as the positive growth result and belong beside it.^[2]

Pituitary responsiveness was tested at the end.^[2] The plasma GH response to a provocative intravenous dose of ipamorelin was marginally reduced after 15 days of treatment, while the response to GHRH was unchanged.^[2] Pituitary GH content was unchanged.^[2] The authors close by saying whether ipamorelin or other secretagogues have a place in treating children with growth retardation requires demonstration in future clinical studies.^[2]

The Class in Human Studies

A 2018 review of growth hormone secretagogues in human subjects states that few long-term, rigorously controlled studies have examined their efficacy and safety.^[3] It reports the class as well tolerated, with some concern for increases in blood glucose because of decreases in insulin sensitivity.^[3] It closes by saying long-term safety, including cancer incidence and mortality, still needs evaluation.^[3]

State of the Evidence

Three things shape this page, and the first is what selectivity was measured against.

The finding is that ipamorelin did not raise ACTH or cortisol above the levels seen after GHRH stimulation, in conscious swine.^[1] GHRH itself is a secretagogue, so the comparison is against an active reference rather than against nothing. The result is a genuine contrast with GHRP-6 and GHRP-2, which were raised in the same experiment.^[1] It is not a claim that the compound leaves those hormones untouched.

The second is that both primary sources come from the same program. References 1 and 2 are Novo Nordisk work on their own compound.^[2] No independent laboratory has replicated the selectivity result in this set, and that is the open question on the page's headline claim.

The third is that the rat study's nulls matter for how the growth result is read. Bone lengthened and body weight rose, while IGF-1, binding proteins and bone turnover markers did not move.^[2] Pituitary responsiveness to the compound itself declined slightly over 15 days.^[2] No human study of this compound appears in this set.^[3]