Key papers ✓ 4~ 1? 2

• ~ Mixed human RCTClin Endocrinol (Oxf) · 2002

  The combined administration of GH-releasing peptide-2 (GHRP-2), TRH and GnRH to men with prolonged critical illness evokes superior endocrine and metabolic effects compared to treatment with GHRP-2 alone.

  Humanssize not reportedRandomizedPlacebo-controlled5 days

  Randomized placebo-controlled trial

  In 33 critically ill men, 5 days of GHRP-2 infusion reactivated GH secretion and normalized IGF-I, but alone it did not reduce protein breakdown (ureagenesis) and it raised serum lactate and white cell count; combination with TRH and GnRH worked better.

  Key resultOnly GnRH pulses with GHRP-2 + TRH infusion increased testosterone significantly (peak increase of + 312%); ureagenesis reduced by GHRP-2 + TRH + GnRH (P = 0.01) but not GHRP-2 alone

  Study details

  Studied

  Men with prolonged critical illness

  Compared with

  Placebo, GHRP-2 alone, GHRP-2 + TRH

  Main outcome

  GH, TSH and LH secretion; IGF-I, thyroid hormones, testosterone, metabolic markers

  Sample

  33 men with prolonged critical illness randomized to placebo (7), GHRP-2 (9), GHRP-2 + TRH (9) or GHRP-2 + TRH + GnRH (8); 50 matched controls at baseline

  Authors' conclusion

  Coadministration of GHRP-2, TRH and GnRH reactivated the GH, TSH and LH axes and gave beneficial metabolic effects absent with GHRP-2 alone, underlining the value of correcting multiple hormonal deficits.

  Limitations

  Small groups (7 to 9 per arm).

  DOI 10.1046/j.1365-2265.2002.01255.xPubMed 12030918
• ✓ Positive human trialEur J Endocrinol · 2007

  A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency.

  Humanssize not reported2 hours of sampling

  Diagnostic validation study with a single IV 100 microg GHRP-2 dose

  In 77 healthy adults and 58 GH-deficient patients, an IV GHRP-2 test separated the groups (peak GH 84.6 vs 1.36 µg/l) with good reproducibility, supporting its use as a diagnostic alternative to the insulin tolerance test.

  Key resultPeak GH was 1.36 ± 2.60 microg/l in patients vs 84.6 ± 60.9 microg/l in healthy subjects (P<0.001); a 15 microg/l cut-off corresponded to 3 microg/l on the ITT

  Study details

  Studied

  Healthy adults and patients with peak GH < 3 microg/l by insulin tolerance test

  Compared with

  Insulin tolerance test

  Main outcome

  Peak GH after GHRP-2 and diagnostic cut-off

  Sample

  77 healthy subjects and 58 patients with GH deficiency

  Authors' conclusion

  The GHRP-2 test was reproducible and mildly influenced by age and adiposity; severe GH deficiency could be diagnosed reliably with a 15 microg/l peak GH cut-off.

  Limitations

  Responses slightly lower in elderly and adiposity.

  DOI 10.1530/EJE-07-0066PubMed 17609397
• ✓ Positive human trialJ Endocrinol · 1997

  Treatment effects of intranasal growth hormone releasing peptide-2 in children with short stature.

  Humans15 people6 months (six children 18-24 months)

  Open treatment study of intranasal GHRP-2

  In 15 short children (uncontrolled), intranasal GHRP-2 for 6 months raised height velocity from 3.7 to 6.1 cm/year, sustained at 18-24 months in 6 children, without changing IGF-1; well tolerated.

  Key resultHeight velocity rose from 3.7 ± 0.2 to 6.1 ± 0.3 cm/year at 6 months; GHBP rose from 439 ± 63 to 688 ± 48 pmol/l; no significant change in IGF-1 or IGFBP-3

  Study details

  Studied

  Children with short stature (half GH deficient, half idiopathic)

  Compared with

  Pre-treatment height velocity

  Main outcome

  Height velocity, IGF-1, IGFBP-3, GHBP

  Sample

  15 children with short stature

  Authors' conclusion

  Intranasal GHRP-2 was well tolerated and produced a modest but significant increase in growth velocity.

  Limitations

  No control group; small sample.

  DOI 10.1677/joe.0.1550079PubMed 9390009
• ✓ Positive human trialJ Clin Endocrinol Metab · 1998

  Pharmacokinetics and pharmacodynamics of growth hormone-releasing peptide-2: a phase I study in children.

  Humanssize not reportedNo control group2 hours of blood sampling

  Phase I pharmacokinetic/pharmacodynamic study, single 1 microg/kg IV dose

  In 10 short prepubertal children, a single IV dose of GHRP-2 produced a predictable, significant GH rise; GHRP-2 half-life was about 0.55 h.

  Key resultGHRP-2 elimination half-life 0.55 ± 0.14 h and Cmax 7.4 ± 3.8 ng/mL; GH Cmax 50.7 ± 17.2 ng/mL; EC50 1.09 ± 0.59 ng/mL

  Study details

  Studied

  Prepubertal children with short stature (mean age 7.7 ± 2.4 years)

  Main outcome

  GHRP-2 and GH pharmacokinetics and pharmacodynamics

  Sample

  Ten prepubertal children (nine boys, one girl)

  Authors' conclusion

  GHRP-2 produced a predictable, significant rise in plasma GH; defining EC50 will allow PK/PD evaluation of extravascular dosing regimens in children.

  Limitations

  Single dose, small sample, no control.

  DOI 10.1210/jcem.83.4.4744PubMed 9543135
• ? Inconclusive human RCTEur J Endocrinol · 2010

  Secretagogue type, sex-steroid milieu, and abdominal visceral adiposity individually determine secretagogue-stimulated cortisol secretion.

  Humans42 peopleRandomizedPlacebo-controlledDouble-blind5 hours of sampling per challenge

  Double-blind placebo-controlled randomized study with secretagogue challenges (archival sera)

  In 42 healthy men, an IV GHRP-2 dose raised peak cortisol (616 vs ~420 nmol/l with saline, GHRH or somatostatin), showing GHRP-2 is not GH-selective.

  Key resultPeak cortisol 868 ± 27 nmol/l with triple stimulus vs 616 ± 42 with GHRP-2 vs 420 ± 21 for saline/SS/GHRH (secretagogue type P<0.001)

  Study details

  Studied

  Healthy men given placebo, testosterone, testosterone + dutasteride, or testosterone + anastrozole

  Compared with

  Saline, GHRH, somatostatin

  Main outcome

  Stimulated cortisol secretion

  Sample

  42 healthy men in four sex-steroid groups

  Authors' conclusion

  Age, DHT concentrations, visceral fat and secretagogue type influence pulsatile cortisol secretion in men; ACTH and native ghrelin action need study.

  Limitations

  Analysis of archival sera; men only.

  DOI 10.1530/EJE-10-0149PubMed 20299490Free full text
• ? Inconclusive reviewSex Med Rev · 2018

  The Safety and Efficacy of Growth Hormone Secretagogues.

  No new data

  Literature review

  Review of human GH secretagogue studies: few long-term controlled studies exist; they appear well tolerated but may raise blood glucose via reduced insulin sensitivity, and long-term safety (incl. cancer) is unknown.

  Study details

  Studied

  Humans receiving GH secretagogues (GH-releasing peptides, ibutamoren)

  Main outcome

  Safety and efficacy of GH secretagogues

  Sample

  Review of clinical studies (number not stated)

  Authors' conclusion

  Few long-term controlled studies exist; GHSs are well tolerated with some concern for raised blood glucose via reduced insulin sensitivity, and long-term safety, including cancer, needs study.

  Limitations

  Few long-term, rigorously controlled studies.

  DOI 10.1016/j.sxmr.2017.02.004PubMed 28400207Free full text
• ✓ Positive animalArzneimittelforschung · 2004

  Pharmacological characteristics of KP-102 (GHRP-2), a potent growth hormone-releasing peptide.

  Animalssize not reportedThree weeks of administration in the growth study

  In vivo and in vitro pharmacology of KP-102 (GHRP-2)

  In rats and dogs, GHRP-2 released GH more potently than GHRH in conscious animals and accelerated growth over 3 weeks, but also stimulated ACTH and corticosterone.

  Study details

  Studied

  Conscious and anesthetized rats, hypophysectomized and median eminence-lesioned rats, dogs, cultured rat pituitary cells

  Compared with

  GHRH

  Main outcome

  GH release

  Authors' conclusion

  KP-102 (GHRP-2) showed specific GH-releasing activity with slight ACTH secretion, and its activity was stable compared with exogenous GHRH.

  Limitations

  Animal and in vitro study.

  DOI 10.1055/s-0031-1297041PubMed 15646370

Reported side effects

• reportedIncreased cortisol release [ref]
• reportedRaised serum lactate and white blood cell count (critically ill patients) [ref]

Human exposure in published trials is short-term (single doses to months); no long-term safety data exist.

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.