Ipamorelin

1. Studied for

   Post-surgical ileus in people: the one published controlled trial, which was negative

   A multicentre, double-blind, placebo-controlled phase 2 trial gave adults having small and large bowel resection either intravenous ipamorelin or placebo twice a day from the first day after surgery until day 7 or discharge. One hundred seventeen adults were enrolled and 114 made up the safety and analysis populations. The main measure, median time from the first infusion to tolerating a standard solid meal, was 25.3 hours on the peptide and 32.6 hours on placebo, a difference that did not reach statistical significance (p = 0.15). Side effects of any kind were recorded in 87.5 percent of the peptide group and 94.8 percent of the placebo group. The authors reported the regimen was well tolerated and that there were no significant differences between the peptide and placebo in the key or secondary efficacy analyses, and listed as a limitation that the study was small with a broad range of underlying conditions. This is essential context: the only published controlled human efficacy trial of ipamorelin did not work, and it tested gut motility rather than anything growth-hormone-related. The tolerability figures belong to that intravenous hospital setting and to that population, and transfer to nothing else. HUMAN in a human trial (multicentre randomised double-blind placebo-controlled phase 2; 117 enrolled, 114 analysed) Preclinical strong A controlled study in people, or convergent results from more than one independent laboratory across more than one experimental system. It rates how well the work was done, never whether the result was favorable: the one controlled human efficacy trial on this page carries this badge and it missed its main endpoint. Open for the full finding and the paper it came from.

   In the literature

   Post-surgical ileus in people: the one published controlled trial, which was negative

   A multicentre, double-blind, placebo-controlled phase 2 trial gave adults having small and large bowel resection either intravenous ipamorelin or placebo twice a day from the first day after surgery until day 7 or discharge. One hundred seventeen adults were enrolled and 114 made up the safety and analysis populations. The main measure, median time from the first infusion to tolerating a standard solid meal, was 25.3 hours on the peptide and 32.6 hours on placebo, a difference that did not reach statistical significance (p = 0.15). Side effects of any kind were recorded in 87.5 percent of the peptide group and 94.8 percent of the placebo group. The authors reported the regimen was well tolerated and that there were no significant differences between the peptide and placebo in the key or secondary efficacy analyses, and listed as a limitation that the study was small with a broad range of underlying conditions. This is essential context: the only published controlled human efficacy trial of ipamorelin did not work, and it tested gut motility rather than anything growth-hormone-related. The tolerability figures belong to that intravenous hospital setting and to that population, and transfer to nothing else.^{References 1, 2}

   Modelin a human trial (multicentre randomised double-blind placebo-controlled phase 2; 117 enrolled, 114 analysed)

   Confidence: strong

   A controlled study in people, or convergent results from more than one independent laboratory across more than one experimental system. It rates how well the work was done, never whether the result was favorable: the one controlled human efficacy trial on this page carries this badge and it missed its main endpoint.

   Source

   Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group. Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Int J Colorectal Dis. 2014 Dec;29(12):1527-34. DOI: 10.1007/s00384-014-2030-8. PMID: 25331030. ClinicalTrials.gov NCT00672074.

   PubMed 25331030 Source

   How this citation was checked

   Re-resolved live on 2026-07-28. PubMed efetch of PMID 25331030 returned authors Beck DE, Sweeney WB, McCarter MD plus the collective name 'Ipamorelin 201 Study Group'; Int J Colorectal Dis 2014 Dec, v29 i12 pp1527-34, DOI field 10.1007/s00384-014-2030-8. Crossref on that DOI returned 2014, International Journal of Colorectal Disease, v29 i12 p1527-1534, matching title. The abstract read in full this pass supplies 117 enrolled, 114 in the safety and modified intent-to-treat populations, twice daily on postoperative day 1 to 7 or hospital discharge, 'Median time to first tolerated meal was 25.3 and 32.6 h in the ipamorelin and placebo groups, respectively (p = 0.15)', the 87.5 percent and 94.8 percent adverse-event figures, and verbatim 'There were no significant differences between ipamorelin and placebo in the key and secondary efficacy analyses.' The ClinicalTrials.gov v2 API for NCT00672074, queried live the same day, returned COMPLETED, PHASE2, enrollment 117 ACTUAL, lead sponsor Helsinn Therapeutics (U.S.), Inc, completion 2009-12 ACTUAL, hasResults false. The mg/kg figure that appears three times in the abstract has been removed from this entry.

2. Studied for

   Human pharmacokinetics and the shape of the growth hormone response

   In a phase 1 study in healthy male volunteers, given as short intravenous infusions at five ascending rates with eight men at each rate, blood levels of the peptide rose in proportion to the amount given and it cleared with a half-life of about 2 hours (clearance 0.078 L/h/kg, steady-state volume of distribution 0.22 L/kg). Growth hormone came out as one single burst that peaked around 40 minutes and then fell away to negligible levels at every level tested; the concentration producing half the maximum growth hormone response was 214 nmol/L. How much growth hormone each man made varied more between individuals than the handling of the peptide itself did. This is the main published human dataset for the compound, and it measured only where the peptide goes and what hormone came out, not any clinical result. in a human phase 1 pharmacokinetic and pharmacodynamic study (healthy male volunteers) Preclinical strong A controlled study in people, or convergent results from more than one independent laboratory across more than one experimental system. It rates how well the work was done, never whether the result was favorable: the one controlled human efficacy trial on this page carries this badge and it missed its main endpoint. Open for the full finding and the paper it came from.

   In the literature

   Human pharmacokinetics and the shape of the growth hormone response

   In a phase 1 study in healthy male volunteers, given as short intravenous infusions at five ascending rates with eight men at each rate, blood levels of the peptide rose in proportion to the amount given and it cleared with a half-life of about 2 hours (clearance 0.078 L/h/kg, steady-state volume of distribution 0.22 L/kg). Growth hormone came out as one single burst that peaked around 40 minutes and then fell away to negligible levels at every level tested; the concentration producing half the maximum growth hormone response was 214 nmol/L. How much growth hormone each man made varied more between individuals than the handling of the peptide itself did. This is the main published human dataset for the compound, and it measured only where the peptide goes and what hormone came out, not any clinical result.^{References 3}

   Modelin a human phase 1 pharmacokinetic and pharmacodynamic study (healthy male volunteers)

   Confidence: strong

   A controlled study in people, or convergent results from more than one independent laboratory across more than one experimental system. It rates how well the work was done, never whether the result was favorable: the one controlled human efficacy trial on this page carries this badge and it missed its main endpoint.

   Source

   Gobburu JV, Agerso H, Jusko WJ, Ynddal L. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharm Res. 1999 Sep;16(9):1412-6. DOI: 10.1023/a:1018955126402. PMID: 10496658.

   PubMed 10496658

   How this citation was checked

   Re-resolved live on 2026-07-28. PubMed efetch of PMID 10496658 returned authors Gobburu JV, Agerso H, Jusko WJ, Ynddal L; Pharm Res 1999 Sep, v16 i9 pp1412-6, DOI field 10.1023/a:1018955126402. Crossref on that DOI returned first author Gobburu, 1999, Pharmaceutical Research, v16 i9 p1412-1416, matching title. The abstract read in full this pass confirms the dose-escalation design with 5 infusion rates over 15 minutes and eight healthy male subjects at each level, dose-proportional PK, terminal half-life 2 hours, clearance 0.078 L/h/kg, Vss 0.22 L/kg, a single episode of GH release peaking at 0.67 hours, SC50 214 nmol/L, and the sentence that inter-individual variability of the PD parameters was larger than that of the PK parameters. The abstract's nmol/kg infusion amounts are deliberately not reproduced.

3. Studied for

   Receptor mechanism and pituitary-hormone selectivity (the defining characterization study)

   In cultured rat pituitary cells and then in anaesthetised rats and conscious pigs, ipamorelin made the pituitary release growth hormone about as strongly as the older peptide GHRP-6 (half-maximal concentration 1.3 +/- 0.4 nmol/L and maximum effect 85 +/- 5 percent, against 2.2 +/- 0.3 nmol/L and 100 percent for GHRP-6), and blocking experiments showed it works through the ghrelin-type receptor rather than the GHRH receptor. In the pigs, the researchers watched a panel of other pituitary hormones: none of the compounds tested changed FSH, LH, prolactin or TSH, and while GHRP-6 and GHRP-2 pushed up ACTH and cortisol, ipamorelin did not raise them to levels significantly different from a GHRH reference stimulus. That comparison against GHRH is the exact claim the paper makes; it is not a claim that ACTH and cortisol stayed flat, and it has never been tested as a hormone-selectivity endpoint in people. in cultured rat pituitary cells, plus anaesthetised rat and conscious pig studies Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Receptor mechanism and pituitary-hormone selectivity (the defining characterization study)

   In cultured rat pituitary cells and then in anaesthetised rats and conscious pigs, ipamorelin made the pituitary release growth hormone about as strongly as the older peptide GHRP-6 (half-maximal concentration 1.3 +/- 0.4 nmol/L and maximum effect 85 +/- 5 percent, against 2.2 +/- 0.3 nmol/L and 100 percent for GHRP-6), and blocking experiments showed it works through the ghrelin-type receptor rather than the GHRH receptor. In the pigs, the researchers watched a panel of other pituitary hormones: none of the compounds tested changed FSH, LH, prolactin or TSH, and while GHRP-6 and GHRP-2 pushed up ACTH and cortisol, ipamorelin did not raise them to levels significantly different from a GHRH reference stimulus. That comparison against GHRH is the exact claim the paper makes; it is not a claim that ACTH and cortisol stayed flat, and it has never been tested as a hormone-selectivity endpoint in people.^{References 4}

   Modelin cultured rat pituitary cells, plus anaesthetised rat and conscious pig studies

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Raun K, Hansen BS, Johansen NL, Thogersen H, Madsen K, Ankersen M, Andersen PH. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998 Nov;139(5):552-61. DOI: 10.1530/eje.0.1390552. PMID: 9849822.

   PubMed 9849822

   How this citation was checked

   Re-resolved live on 2026-07-28. PubMed efetch of PMID 9849822 returned authors Raun K, Hansen BS, Johansen NL, Thogersen H, Madsen K, Ankersen M, Andersen PH; Eur J Endocrinol 1998 Nov, v139 i5 pp552-61, DOI field 10.1530/eje.0.1390552. Crossref on that DOI returned first author Raun, 1998, European Journal of Endocrinology, v139 i5 p552-561, same title. The full abstract was read this pass and contains verbatim 'ECs) = 1.3+/-0.4nmol/l and Emax = 85+/-5% vs 2.2+/-0.3nmol/l and 100%', the antagonist-profiling conclusion that it 'stimulates GH release via a GHRP-like receptor', 'None of the GH secretagogues tested affected FSH, LH, PRL or TSH plasma levels', and 'ipamorelin did not release ACTH or cortisol in levels significantly different from those observed following GHRH stimulation'. Dose figures present in the abstract are deliberately not reproduced.

4. Studied for

   Body fat and food intake in mice: a result that runs opposite to fat-loss marketing

   Growth hormone and ipamorelin were given twice daily under the skin to mice that could not make their own growth hormone and to mice that could. The peptide produced a small rise in body weight, about 15 percent by two weeks, which did not grow further by nine weeks, while growth hormone raised body weight markedly in both groups. The peptide increased fat pad weight relative to body weight in both mouse types, and two weeks of secretagogue exposure (this peptide or GHRP-6) increased the proportion of the body that was fat on whole-body scanning in the growth-hormone-intact mice. Growth hormone did the opposite: it lowered relative fat mass in the deficient mice and did nothing in the intact ones. The secretagogues, but not growth hormone, raised blood leptin and food intake. The authors concluded that secretagogues increase body fat by mechanisms that do not run through growth hormone and that may include simply eating more. This mouse result is the direct evidence against fat-loss and body-composition claims made for this compound. in mouse studies (growth-hormone-deficient and growth-hormone-intact mice, twice-daily subcutaneous exposure up to 9 weeks) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Body fat and food intake in mice: a result that runs opposite to fat-loss marketing

   Growth hormone and ipamorelin were given twice daily under the skin to mice that could not make their own growth hormone and to mice that could. The peptide produced a small rise in body weight, about 15 percent by two weeks, which did not grow further by nine weeks, while growth hormone raised body weight markedly in both groups. The peptide increased fat pad weight relative to body weight in both mouse types, and two weeks of secretagogue exposure (this peptide or GHRP-6) increased the proportion of the body that was fat on whole-body scanning in the growth-hormone-intact mice. Growth hormone did the opposite: it lowered relative fat mass in the deficient mice and did nothing in the intact ones. The secretagogues, but not growth hormone, raised blood leptin and food intake. The authors concluded that secretagogues increase body fat by mechanisms that do not run through growth hormone and that may include simply eating more. This mouse result is the direct evidence against fat-loss and body-composition claims made for this compound.^{References 5}

   Modelin mouse studies (growth-hormone-deficient and growth-hormone-intact mice, twice-daily subcutaneous exposure up to 9 weeks)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Lall S, Tung LY, Ohlsson C, Jansson JO, Dickson SL. Growth hormone (GH)-independent stimulation of adiposity by GH secretagogues. Biochem Biophys Res Commun. 2001 Jan 12;280(1):132-8. DOI: 10.1006/bbrc.2000.4065. PMID: 11162489.

   PubMed 11162489

   How this citation was checked

   Re-resolved live on 2026-07-28. PubMed efetch of PMID 11162489 returned authors Lall S, Tung LY, Ohlsson C, Jansson JO, Dickson SL; Biochem Biophys Res Commun 2001 Jan 12, v280 i1 pp132-8, DOI field 10.1006/bbrc.2000.4065. Crossref on that DOI returned first author Lall, 2001, Biochemical and Biophysical Research Communications, v280 i1 p132-138, matching title. The abstract read in full this pass supplies verbatim 'ipamorelin induced a small (15%) increase in body weight by 2 weeks, that was not further augmented by 9 weeks', the fat pad and DEXA relative-fat results, 'GH decreased relative fat mass in lit/lit mice and had no effect in GH-intact mice', 'Treatment with GHS, but not GH, increased serum leptin and food intake in GH-intact mice', and the conclusion 'GHSs increase body fat by GH-independent mechanisms that may include increased feeding.'

5. Studied for

   Longitudinal bone growth in rodents, with an explicit dissociation from IGF-1

   In adult female rats given the peptide under the skin three times a day for 15 days at three different levels, the growth plate of the shin bone laid down new bone faster, and faster at each higher level: 42 micrometres per day in the vehicle group against 44, 50 and 52 micrometres per day in the 3 groups given the peptide (P<0.0001), with a matching effect on weight gain. In the same rats, the peptide did not change total IGF-1, IGF binding proteins, or blood markers of bone build-up and breakdown, and the number of bone-resorbing cells counted in the shin did not change significantly. This is the single most important corrective in this dossier against IGF-1 marketing claims: bone lengthened while total IGF-1 did not move. in rat studies (adult female rats, 15 days of repeated subcutaneous exposure) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Longitudinal bone growth in rodents, with an explicit dissociation from IGF-1

   In adult female rats given the peptide under the skin three times a day for 15 days at three different levels, the growth plate of the shin bone laid down new bone faster, and faster at each higher level: 42 micrometres per day in the vehicle group against 44, 50 and 52 micrometres per day in the 3 groups given the peptide (P<0.0001), with a matching effect on weight gain. In the same rats, the peptide did not change total IGF-1, IGF binding proteins, or blood markers of bone build-up and breakdown, and the number of bone-resorbing cells counted in the shin did not change significantly. This is the single most important corrective in this dossier against IGF-1 marketing claims: bone lengthened while total IGF-1 did not move.^{References 6}

   Modelin rat studies (adult female rats, 15 days of repeated subcutaneous exposure)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Johansen PB, Nowak J, Skjaerbaek C, Flyvbjerg A, Andreassen TT, Wilken M, Orskov H. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Horm IGF Res. 1999 Apr;9(2):106-13. DOI: 10.1054/ghir.1999.9998. PMID: 10373343.

   PubMed 10373343

   How this citation was checked

   Re-resolved live on 2026-07-28. PubMed efetch of PMID 10373343 returned the exact author list above; Growth Horm IGF Res 1999 Apr, v9 i2 pp106-13, DOI field 10.1054/ghir.1999.9998. Crossref on that DOI returned first author Johansen, 1999, Growth Hormone & IGF Research, v9 i2 p106-113, matching title. The abstract read in full this pass contains verbatim 'increased LGR from 42 microm/day in the vehicle group to 44, 50, and 52 microm/day in the treatment groups (P<0.0001)' and 'The treatment did not affect total IGF-I levels, IGFBPs, or serum markers of bone formation and resorption', plus the unchanged tartrate-resistant acid phosphatase-positive cell count. The abstract's microgram-per-day amounts are deliberately not reproduced, and the paper's closing speculation about treating children with growth retardation is deliberately not carried forward.

6. Studied for

   Bone mineral content in rodents: bigger bones, not denser bone

   In young adult female rats given a continuous supply of the peptide, GHRP-6, growth hormone or nothing for 12 weeks by implanted pump, with whole-body scans every four weeks and detailed bone analysis afterwards, each of the 3 compounds raised body weight and raised the total mineral content of the shin and spine bones on the scan. But once that mineral content was corrected for the extra body weight, the difference disappeared. Two-dimensional bone mineral density of the shin did go up; total and spinal two-dimensional density did not. The measurements that actually distinguish bigger bone from denser bone all pointed the same way: true volumetric density measured by CT and by water displacement was unchanged, and while ash weight rose, mineral concentration did not. The authors concluded the extra mineral was there because the bones themselves had grown larger. This is a bone-growth result in rats and specifically not a bone-densification result. in rat studies (adult female Sprague-Dawley rats, 12 weeks of continuous subcutaneous infusion) with laboratory analysis of the bones afterwards Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Bone mineral content in rodents: bigger bones, not denser bone

   In young adult female rats given a continuous supply of the peptide, GHRP-6, growth hormone or nothing for 12 weeks by implanted pump, with whole-body scans every four weeks and detailed bone analysis afterwards, each of the 3 compounds raised body weight and raised the total mineral content of the shin and spine bones on the scan. But once that mineral content was corrected for the extra body weight, the difference disappeared. Two-dimensional bone mineral density of the shin did go up; total and spinal two-dimensional density did not. The measurements that actually distinguish bigger bone from denser bone all pointed the same way: true volumetric density measured by CT and by water displacement was unchanged, and while ash weight rose, mineral concentration did not. The authors concluded the extra mineral was there because the bones themselves had grown larger. This is a bone-growth result in rats and specifically not a bone-densification result.^{References 7}

   Modelin rat studies (adult female Sprague-Dawley rats, 12 weeks of continuous subcutaneous infusion) with laboratory analysis of the bones afterwards

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Svensson J, Lall S, Dickson SL, Bengtsson BA, Romer J, Ahnfelt-Ronne I, Ohlsson C, Jansson JO. The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. J Endocrinol. 2000 Jun;165(3):569-77. DOI: 10.1677/joe.0.1650569. PMID: 10828840.

   PubMed 10828840

   How this citation was checked

   Re-resolved live on 2026-07-28. PubMed efetch of PMID 10828840 returned the exact author list above; J Endocrinol 2000 Jun, v165 i3 pp569-77, DOI field 10.1677/joe.0.1650569. Crossref on that DOI returned first author Svensson, 2000, Journal of Endocrinology, v165 i3 p569-577, matching title. The abstract was read in full this pass, and the earlier certification's fidelity objection has been fixed here: the abstract states 'Tibial area bone mineral density (BMD, BMC/area) was increased, but total and vertebral area BMDs were unchanged', which this entry now reports rather than omitting. Also verbatim: 'total BMC corrected for the increase in body weight (total BMC:body weight ratio) was unaffected', 'the cortical volumetric BMD was unchanged', 'no effect was seen on the volumetric BMDs as measured by Archimedes' principle', 'Ash weight was increased by all treatments, but the mineral concentration was unchanged', and the conclusion that the increases 'were due to an increased growth of the bones with increased bone dimensions, whereas the volumetric BMD was unchanged'. The abstract's mg/kg per day amounts are deliberately not reproduced.

7. Studied for

   Steroid co-exposure: bone formation and muscle force in rodents

   Eight-month-old female rats were given a synthetic steroid (methylprednisolone), ipamorelin, or both together for three months. In the animals that got the steroid plus the peptide, the maximum force their calf muscles could produce was significantly higher, and the rate at which new bone was laid down on the outer bone surface was four times higher, both compared with the animals that got the steroid alone. The authors concluded that the loss of muscle strength and bone formation caused by the steroid was counteracted by giving the secretagogue at the same time. Read the direction carefully: this is a rat model of steroid-driven wasting, and it describes offsetting a drug-induced deficit, not improving on a normal animal. in rat studies (8-month-old female rats, 3 months of steroid co-administration) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Steroid co-exposure: bone formation and muscle force in rodents

   Eight-month-old female rats were given a synthetic steroid (methylprednisolone), ipamorelin, or both together for three months. In the animals that got the steroid plus the peptide, the maximum force their calf muscles could produce was significantly higher, and the rate at which new bone was laid down on the outer bone surface was four times higher, both compared with the animals that got the steroid alone. The authors concluded that the loss of muscle strength and bone formation caused by the steroid was counteracted by giving the secretagogue at the same time. Read the direction carefully: this is a rat model of steroid-driven wasting, and it describes offsetting a drug-induced deficit, not improving on a normal animal.^{References 8}

   Modelin rat studies (8-month-old female rats, 3 months of steroid co-administration)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Andersen NB, Malmlof K, Johansen PB, Andreassen TT, Ortoft G, Oxlund H. The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats. Growth Horm IGF Res. 2001 Oct;11(5):266-72. DOI: 10.1054/ghir.2001.0239. PMID: 11735244.

   PubMed 11735244

   How this citation was checked

   Re-resolved live on 2026-07-28. PubMed efetch of PMID 11735244 returned the exact author list above; Growth Horm IGF Res 2001 Oct, v11 i5 pp266-72, DOI field 10.1054/ghir.2001.0239. Crossref on that DOI returned first author Andersen, 2001, Growth Hormone & IGF Research, v11 i5 p266-272, matching title. The abstract read in full this pass confirms 8-month-old female rats, 3 months of subcutaneous injection, and verbatim 'The maximum tetanic tension was increased significantly, and the periosteal bone formation rate increased four-fold in animals injected with GC and GHS in combination, compared with the group injected with GC alone', plus the conclusion sentence. The abstract's mg/kg and microgram/kg amounts are deliberately not reproduced.

8. Studied for

   Nitrogen balance and liver urea production under steroid-induced wasting

   Five groups of rats were compared over seven days: free-fed controls, food-matched controls, a steroid (prednisolone) alone, steroid plus growth hormone, and steroid plus ipamorelin. The steroid alone pushed the liver to burn off more nitrogen as urea, switched up the urea-cycle genes, and drove the animals into negative nitrogen balance with less nitrogen in their organs. Added to the steroid, ipamorelin cut the liver's urea-nitrogen capacity by 20 percent (P<0.05), turned down the urea-cycle genes, brought nitrogen balance back to neutral, and normalised or improved organ nitrogen. Growth hormone itself did more in the same experiment (a 33 percent cut in urea-nitrogen capacity and a 2.5-fold improvement in nitrogen balance), and the authors concluded that both counteracted the steroid-driven nitrogen wasting, though at the amounts given, less efficiently by the secretagogue. in rat studies (rats given prednisolone, 7 days, with food-matched and growth-hormone comparison groups) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Nitrogen balance and liver urea production under steroid-induced wasting

   Five groups of rats were compared over seven days: free-fed controls, food-matched controls, a steroid (prednisolone) alone, steroid plus growth hormone, and steroid plus ipamorelin. The steroid alone pushed the liver to burn off more nitrogen as urea, switched up the urea-cycle genes, and drove the animals into negative nitrogen balance with less nitrogen in their organs. Added to the steroid, ipamorelin cut the liver's urea-nitrogen capacity by 20 percent (P<0.05), turned down the urea-cycle genes, brought nitrogen balance back to neutral, and normalised or improved organ nitrogen. Growth hormone itself did more in the same experiment (a 33 percent cut in urea-nitrogen capacity and a 2.5-fold improvement in nitrogen balance), and the authors concluded that both counteracted the steroid-driven nitrogen wasting, though at the amounts given, less efficiently by the secretagogue.^{References 9}

   Modelin rat studies (rats given prednisolone, 7 days, with food-matched and growth-hormone comparison groups)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Aagaard NK, Grofte T, Greisen J, Malmlof K, Johansen PB, Gronbaek H, Orskov H, Tygstrup N, Vilstrup H. Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats. Growth Horm IGF Res. 2009 Oct;19(5):426-31. DOI: 10.1016/j.ghir.2009.01.001. PMID: 19231263.

   PubMed 19231263

   How this citation was checked

   Re-resolved live on 2026-07-28. PubMed efetch of PMID 19231263 returned authors Aagaard NK, Grofte T, Greisen J, Malmlof K, Johansen PB, Gronbaek H, Orskov H, Tygstrup N, Vilstrup H, with DOI field 10.1016/j.ghir.2009.01.001; Growth Horm IGF Res 2009 Oct, v19 i5 pp426-31. Crossref on that DOI returned first author Aagaard, 2009, Growth Hormone & IGF Research, v19 i5 p426-431, matching title. The abstract read in full this pass supplies verbatim 'Ipamorelin reduced CUNS by 20% (p<0.05)', 'co-administration of GH reduced CUNS by 33% (p<0.01), normalized urea cycle gene expression, improved N-balance 2.5-fold', and 'though at the doses given less efficiently by the latter'. The earlier draft's DOI 10.1016/j.ghir.2008.12.006 and its corrupted author string were dropped in the previous pass and are confirmed absent here. The abstract's mg/kg per day amounts are deliberately not reproduced, as is the paper's closing speculation about treating steroid-induced catabolism.

9. Studied for

   Whether steroids block the growth hormone signal

   In one rat experiment, eight days of a synthetic steroid significantly slowed weight gain (P<0.001) but did not change how much growth hormone the pituitary released when the animals were then challenged with either ipamorelin or GHRH. In a second experiment over ten days, the rats on the steroid lost 13.6 +/- 2.9 g of body weight against 4.0 +/- 3.5 g in saline controls, and the rats given the peptide alongside the steroid lost significantly less (P<0.05): 2.3 +/- 2.0 g in the higher-amount group and 1.6 +/- 2.0 g in the lower-amount group. IGF-1 rose alongside. Note the scope: the IGF-1 rise here happened in rats that were also on a steroid, and a separate rat study found no change in total IGF-1 in animals given nothing else. in rat studies (rats given methylprednisolone; an acute-challenge experiment and a 10-day repeated intravenous experiment) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Whether steroids block the growth hormone signal

   In one rat experiment, eight days of a synthetic steroid significantly slowed weight gain (P<0.001) but did not change how much growth hormone the pituitary released when the animals were then challenged with either ipamorelin or GHRH. In a second experiment over ten days, the rats on the steroid lost 13.6 +/- 2.9 g of body weight against 4.0 +/- 3.5 g in saline controls, and the rats given the peptide alongside the steroid lost significantly less (P<0.05): 2.3 +/- 2.0 g in the higher-amount group and 1.6 +/- 2.0 g in the lower-amount group. IGF-1 rose alongside. Note the scope: the IGF-1 rise here happened in rats that were also on a steroid, and a separate rat study found no change in total IGF-1 in animals given nothing else.^{References 10}

   Modelin rat studies (rats given methylprednisolone; an acute-challenge experiment and a 10-day repeated intravenous experiment)

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Malmlof K, Johansen PB, Haahr PM, Wilken M, Oxlund H. Methylprednisolone does not inhibit the release of growth hormone after intravenous injection of a novel growth hormone secretagogue in rats. Growth Horm IGF Res. 1999 Dec;9(6):445-50. DOI: 10.1054/ghir.1999.0128. PMID: 10629165.

   PubMed 10629165

   How this citation was checked

   Re-resolved live on 2026-07-28. PubMed efetch of PMID 10629165 returned authors Malmlof K, Johansen PB, Haahr PM, Wilken M, Oxlund H; Growth Horm IGF Res 1999 Dec, v9 i6 pp445-50, DOI field 10.1054/ghir.1999.0128. Crossref on that DOI returned first author Malmlof, 1999, Growth Hormone & IGF Research, v9 i6 p445-450, matching title. The abstract read in full this pass supplies the 8-day and 10-day designs, the P<0.001 weight-gain result, and verbatim 'saline treated animals lost 4.0 +/- 3.5 g over the entire experimental period, whereas animals receiving MP lost 13. 6 +/- 2.9 g' and 'losses in body weight were significantly (P< 0.05) reduced to 2.3 +/- 2.0 and 1.6 +/- 2.0 g in animals given the high and low dose of IPA, respectively'. The earlier certification's finding that the two co-treated values were reported without saying which group was which is fixed here: 2.3 g is the higher-amount group and 1.6 g the lower-amount group. The abstract's mg/kg amounts are deliberately not reproduced.

10. Studied for

    Stomach emptying and stomach muscle contraction in a rodent model of post-surgical ileus

    In a separate rat study, fasted adult males had abdominal surgery with intestinal handling and then received the peptide or plain vehicle into a vein. Stomach emptying was measured as how much of a tagged test meal was still in the stomach 15 minutes later: 78 +/- 5 percent remained in the vehicle group against 52 +/- 11 percent with the peptide, a significant acceleration (P<0.05 versus vehicle). Rats that had never had surgery had 44 +/- 6 percent remaining. The paper reports no statistical comparison between the peptide group and the non-surgical group, so no conclusion should be drawn about whether emptying returned to the non-surgical level. Separately, strips of stomach muscle taken from operated rats and hung in an organ bath had lost most of their contraction response to acetylcholine and to electrical stimulation, and both the peptide and ghrelin restored it. The authors read this as the peptide driving stomach contraction through the ghrelin receptor acting on cholinergic excitatory nerves. in rat studies (stomach emptying) plus isolated rat stomach tissue in an organ bath Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

    In the literature

    Stomach emptying and stomach muscle contraction in a rodent model of post-surgical ileus

    In a separate rat study, fasted adult males had abdominal surgery with intestinal handling and then received the peptide or plain vehicle into a vein. Stomach emptying was measured as how much of a tagged test meal was still in the stomach 15 minutes later: 78 +/- 5 percent remained in the vehicle group against 52 +/- 11 percent with the peptide, a significant acceleration (P<0.05 versus vehicle). Rats that had never had surgery had 44 +/- 6 percent remaining. The paper reports no statistical comparison between the peptide group and the non-surgical group, so no conclusion should be drawn about whether emptying returned to the non-surgical level. Separately, strips of stomach muscle taken from operated rats and hung in an organ bath had lost most of their contraction response to acetylcholine and to electrical stimulation, and both the peptide and ghrelin restored it. The authors read this as the peptide driving stomach contraction through the ghrelin receptor acting on cholinergic excitatory nerves.^{References 11}

    Modelin rat studies (stomach emptying) plus isolated rat stomach tissue in an organ bath

    Confidence: moderate

    A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

    Source

    Greenwood-Van Meerveld B, Tyler K, Mohammadi E, Pietra C. Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus. J Exp Pharmacol. 2012 Oct 19;4:149-55. DOI: 10.2147/JEP.S35396. PMID: 27186127. PMCID: PMC4863553.

    PubMed 27186127

    How this citation was checked

    Re-resolved live on 2026-07-28. PubMed efetch of PMID 27186127 returned authors Greenwood-Van Meerveld B, Tyler K, Mohammadi E, Pietra C; J Exp Pharmacol 2012, v4 pp149-55, DOI field 10.2147/JEP.S35396, PMCID PMC4863553. Crossref on that DOI returned first author Greenwood-Van Meerveld, 2012, Journal of Experimental Pharmacology, first page 149, matching title. The abstract read in full this pass supplies the 78 +/- 5, 52 +/- 11 and 44 +/- 6 percent figures and the phrase 'a ghrelin receptor-mediated mechanism involving cholinergic excitatory neurons'. The earlier certification's objection is fixed here: the abstract reports significance only as 'P < 0.05 vs vehicle-treated rat' and performs no test against the nonsurgical group, so the previous draft's inference that emptying was 'accelerated but not returned to the non-surgical level' has been replaced by a statement that no such comparison was reported. The abstract's micromole/kg and micromolar bath amounts are deliberately not reproduced.

11. Studied for

    Gut transit in a rodent model of post-surgical ileus

    Fasted male rats had abdominal surgery with handling of the intestines, then received the peptide, GHRP-6 or plain saline into a vein, either once or repeatedly over two days. Against saline, a single exposure to the peptide or to GHRP-6 shortened the time to the first bowel movement but changed nothing about total stool output, food intake or weight gain measured 48 hours after surgery. Repeated exposure did move those endpoints: total stool output, food intake and weight gain all went up significantly. This is a rat surgical model only, and the single-exposure arm did not shift the cumulative measures. in rat studies (fasted male rats, laparotomy with intestinal manipulation) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

    In the literature

    Gut transit in a rodent model of post-surgical ileus

    Fasted male rats had abdominal surgery with handling of the intestines, then received the peptide, GHRP-6 or plain saline into a vein, either once or repeatedly over two days. Against saline, a single exposure to the peptide or to GHRP-6 shortened the time to the first bowel movement but changed nothing about total stool output, food intake or weight gain measured 48 hours after surgery. Repeated exposure did move those endpoints: total stool output, food intake and weight gain all went up significantly. This is a rat surgical model only, and the single-exposure arm did not shift the cumulative measures.^{References 12}

    Modelin rat studies (fasted male rats, laparotomy with intestinal manipulation)

    Confidence: moderate

    A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

    Source

    Venkova K, Mann W, Nelson R, Greenwood-Van Meerveld B. Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus. J Pharmacol Exp Ther. 2009 Jun;329(3):1110-6. DOI: 10.1124/jpet.108.149211. PMID: 19289567.

    PubMed 19289567

    How this citation was checked

    Re-resolved live on 2026-07-28. PubMed efetch of PMID 19289567 returned authors Venkova K, Mann W, Nelson R, Greenwood-Van Meerveld B; J Pharmacol Exp Ther 2009 Jun, v329 i3 pp1110-6, DOI field 10.1124/jpet.108.149211. Crossref on that DOI returned first author Venkova, 2009, The Journal of Pharmacology and Experimental Therapeutics, v329 i3 p1110-1116, matching title. The abstract read in full this pass confirms the endpoints are time to first bowel movement, fecal pellet output, food intake and body weight, and contains no gastric-emptying, contractility or cholinergic-neuron content, so those findings stay attributed to the separate paper below. The mg/kg and microgram/kg amounts that appear in the abstract have been removed from this entry, as has the paper's closing speculation about ameliorating symptoms in patients.

12. Studied for

    Gut and skin pain sensitivity in rats, and whether it runs through the ghrelin receptor

    Rats were made hypersensitive in the colon by infusing dilute acetic acid, a model that produces the sensitivity without inflaming the colon lining. Ipamorelin, described by the authors as a ghrelin receptor agonist that stays outside the brain, was given into a vein, and a second agonist that does reach the brain was given by mouth. Colon sensitivity was scored by the animals' abdominal response to graded pressure in the rectum, and skin sensitivity by paw withdrawals to a calibrated probe. Compared with vehicle controls, both agonists significantly reduced, but did not abolish, both the gut and the skin hypersensitivity, and both effects were blocked by a ghrelin receptor antagonist, which shows the effect runs through that receptor. This is a rat model only, and the paper reports attenuation rather than abolition. in rat studies (a rat model of non-inflammatory gut hypersensitivity and skin mechanical sensitivity) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

    In the literature

    Gut and skin pain sensitivity in rats, and whether it runs through the ghrelin receptor

    Rats were made hypersensitive in the colon by infusing dilute acetic acid, a model that produces the sensitivity without inflaming the colon lining. Ipamorelin, described by the authors as a ghrelin receptor agonist that stays outside the brain, was given into a vein, and a second agonist that does reach the brain was given by mouth. Colon sensitivity was scored by the animals' abdominal response to graded pressure in the rectum, and skin sensitivity by paw withdrawals to a calibrated probe. Compared with vehicle controls, both agonists significantly reduced, but did not abolish, both the gut and the skin hypersensitivity, and both effects were blocked by a ghrelin receptor antagonist, which shows the effect runs through that receptor. This is a rat model only, and the paper reports attenuation rather than abolition.^{References 13}

    Modelin rat studies (a rat model of non-inflammatory gut hypersensitivity and skin mechanical sensitivity)

    Confidence: moderate

    A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

    Source

    N Mohammadi E, Louwies T, Pietra C, Northrup SR, Greenwood-Van Meerveld B. Attenuation of Visceral and Somatic Nociception by Ghrelin Mimetics. J Exp Pharmacol. 2020 Aug 5;12:267-274. DOI: 10.2147/JEP.S249747. PMID: 32801950. PMCID: PMC7415447.

    PubMed 32801950

    How this citation was checked

    Re-resolved live on 2026-07-28. PubMed efetch of PMID 32801950 returned authors N Mohammadi E, Louwies T, Pietra C, Northrup SR, Greenwood-Van Meerveld B; J Exp Pharmacol 2020, v12 pp267-274, DOI field 10.2147/JEP.S249747, PMCID PMC7415447. Crossref on that DOI returned first author 'N Mohammadi', 2020, Journal of Experimental Pharmacology, Volume 12, p267-274, matching title. The abstract read in full this pass supplies the dilute acetic acid model 'in the absence of colonic epithelial inflammation', the visceromotor and von Frey endpoints, verbatim 'ghrelin mimetics HM01 and ipamorelin significantly attenuated colonic hypersensitivity and somatic allodynia', and 'The anti-nociceptive effects of the ghrelin mimetics were blocked after administration of the ghrelin receptor antagonist H0900.' The paper's closing speculation about treating pain is deliberately not carried forward.

13. Studied for

    Cisplatin-associated weight loss and nausea in ferrets

    Ferrets were given anamorelin, ipamorelin or plain vehicle into the abdominal cavity shortly before cisplatin and then every 24 hours, with behaviour recorded for up to 72 hours and food and water intake measured daily. Given that way, neither compound had any effect on cisplatin-induced vomiting, early or late, but both cut the associated weight loss on the last day of the late phase (48 to 72 hours) by about 24 percent. Anamorelin delivered directly into the brain ventricles did reduce early vomiting by 60 percent while leaving late vomiting alone, which the authors read as evidence that reaching the brain matters for the anti-nausea effect. In strips of ferret intestine in a dish, anamorelin and ipamorelin damped electrically driven contractions by 94.4 percent (half-blocking concentration 14.0 micromolar) and 54.4 percent (11.7 micromolar) respectively. in ferret studies plus isolated ferret intestine in a dish Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

    In the literature

    Cisplatin-associated weight loss and nausea in ferrets

    Ferrets were given anamorelin, ipamorelin or plain vehicle into the abdominal cavity shortly before cisplatin and then every 24 hours, with behaviour recorded for up to 72 hours and food and water intake measured daily. Given that way, neither compound had any effect on cisplatin-induced vomiting, early or late, but both cut the associated weight loss on the last day of the late phase (48 to 72 hours) by about 24 percent. Anamorelin delivered directly into the brain ventricles did reduce early vomiting by 60 percent while leaving late vomiting alone, which the authors read as evidence that reaching the brain matters for the anti-nausea effect. In strips of ferret intestine in a dish, anamorelin and ipamorelin damped electrically driven contractions by 94.4 percent (half-blocking concentration 14.0 micromolar) and 54.4 percent (11.7 micromolar) respectively.^{References 14}

    Modelin ferret studies plus isolated ferret intestine in a dish

    Confidence: moderate

    A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

    Source

    Lu Z, Ngan MP, Liu JYH, Yang L, Tu L, Chan SW, Giuliano C, Lovati E, Pietra C, Rudd JA. The growth hormone secretagogue receptor 1a agonists, anamorelin and ipamorelin, inhibit cisplatin-induced weight loss in ferrets: Anamorelin also exhibits anti-emetic effects via a central mechanism. Physiol Behav. 2024 Oct 1;284:114644. DOI: 10.1016/j.physbeh.2024.114644. PMID: 39043357.

    PubMed 39043357

    How this citation was checked

    Re-resolved live on 2026-07-28. PubMed efetch of PMID 39043357 returned the full ten-author list above, the full title including the subtitle, Physiol Behav 2024 Oct 1, v284, page 114644, DOI field 10.1016/j.physbeh.2024.114644. Crossref on that DOI returned first author Lu, 2024, Physiology & Behavior, v284, article-number 114644, confirming again that the original draft's article number 114639 was wrong. The abstract read in full this pass supplies 'inhibited EFS-induced contractions of isolated ileum by 94.4 % (half-maximal inhibitory concentration [IC50]=14.0 microM) and 54.4 % (IC50=11.7 microM), respectively', 'Neither of compounds administered i.p. had any effect on cisplatin-induced acute or delayed emesis, but both inhibited associated cisplatin-induced weight loss on the last day of delayed phase (48-72 h) by approximately 24 %', and the 60 percent acute-emesis reduction after intracerebroventricular anamorelin. The abstract's mg/kg and microgram amounts are deliberately not reproduced.

14. Studied for

    The growth hormone axis in a diabetic mouse model

    Diabetic and non-diabetic female mice were given the peptide or saline once into a vein, with blood taken before and ten minutes after on day 14, and livers analysed afterwards. Ten minutes after that, growth hormone measured 150 +/- 35 micrograms/L in the diabetic mice against 62 +/- 11 micrograms/L in the non-diabetic mice (P<.05). IGF-1 in the blood was lower in the diabetic animals to begin with and rose after the stimulus only in the non-diabetic animals; in the liver, IGF-1 messenger RNA and protein also rose only in the non-diabetic animals, while the already-low levels in the diabetic mice did not budge. The researchers were using the peptide as a probe to characterise the diabetic model, in which the pituitary over-releases growth hormone while the liver fails to respond to it. The finding is about how that model behaves, not about a benefit of the compound. in mouse studies (streptozotocin-diabetic and non-diabetic female mice, a single intravenous challenge) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

    In the literature

    The growth hormone axis in a diabetic mouse model

    Diabetic and non-diabetic female mice were given the peptide or saline once into a vein, with blood taken before and ten minutes after on day 14, and livers analysed afterwards. Ten minutes after that, growth hormone measured 150 +/- 35 micrograms/L in the diabetic mice against 62 +/- 11 micrograms/L in the non-diabetic mice (P<.05). IGF-1 in the blood was lower in the diabetic animals to begin with and rose after the stimulus only in the non-diabetic animals; in the liver, IGF-1 messenger RNA and protein also rose only in the non-diabetic animals, while the already-low levels in the diabetic mice did not budge. The researchers were using the peptide as a probe to characterise the diabetic model, in which the pituitary over-releases growth hormone while the liver fails to respond to it. The finding is about how that model behaves, not about a benefit of the compound.^{References 15}

    Modelin mouse studies (streptozotocin-diabetic and non-diabetic female mice, a single intravenous challenge)

    Confidence: moderate

    A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

    Source

    Johansen PB, Segev Y, Landau D, Phillip M, Flyvbjerg A. Growth hormone (GH) hypersecretion and GH receptor resistance in streptozotocin diabetic mice in response to a GH secretagogue. Exp Diabesity Res. 2003 Apr-Jun;4(2):73-81. DOI: 10.1155/EDR.2003.73. PMID: 14630569. PMCID: PMC2478601.

    PubMed 14630569

    How this citation was checked

    Re-resolved live on 2026-07-28. PubMed efetch of PMID 14630569 returned authors Johansen PB, Segev Y, Landau D, Phillip M, Flyvbjerg A; Exp Diabesity Res 2003, v4 i2 pp73-81, DOI field 10.1155/EDR.2003.73, PMCID PMC2478601. Crossref on that DOI returned first author Johansen, 2003, v4 i2 p73-81, matching title; Crossref lists the container under the journal's current name, Journal of Diabetes Research, while the article as published appeared in Exp Diabesity Res, and this citation follows the as-published name. Both identifiers point to the same record and this discrepancy is expected, not a defect. The abstract read in full this pass supplies verbatim 'the GH levels were found to be 150 +/- 35 microg/L and 62 +/- 11 microg/L in the diabetic compared to the nondiabetic mice (P <.05)' and the differential IGF-1 response in serum and liver.

15. Studied for

    Where the peptide goes in the body and how it leaves

    Three peptide secretagogues including ipamorelin were compared with GHRP-2 and GHRP-6 in male rats across several routes of administration. After delivery into a vein, blood levels fell in two phases; ipamorelin stood out from the others, clearing from the circulation about five times more slowly than GHRP-6. It left mostly in urine, whereas GHRP-6 left mostly in bile, and 60 to 80 percent of the amount given could be recovered from bile and urine still intact, meaning it resisted being broken down. Sprayed into the nose, about 20 percent of it reached the bloodstream, lower than the roughly 50 percent measured for the three comparison peptides. in rat studies (male rats, several administration routes) Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

    In the literature

    Where the peptide goes in the body and how it leaves

    Three peptide secretagogues including ipamorelin were compared with GHRP-2 and GHRP-6 in male rats across several routes of administration. After delivery into a vein, blood levels fell in two phases; ipamorelin stood out from the others, clearing from the circulation about five times more slowly than GHRP-6. It left mostly in urine, whereas GHRP-6 left mostly in bile, and 60 to 80 percent of the amount given could be recovered from bile and urine still intact, meaning it resisted being broken down. Sprayed into the nose, about 20 percent of it reached the bloodstream, lower than the roughly 50 percent measured for the three comparison peptides.^{References 16}

    Modelin rat studies (male rats, several administration routes)

    Confidence: moderate

    A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

    Source

    Johansen PB, Hansen KT, Andersen JV, Johansen NL. Pharmacokinetic evaluation of ipamorelin and other peptidyl growth hormone secretagogues with emphasis on nasal absorption. Xenobiotica. 1998 Nov;28(11):1083-92. DOI: 10.1080/004982598238976. PMID: 9879640.

    PubMed 9879640

    How this citation was checked

    Re-resolved live on 2026-07-28. PubMed efetch of PMID 9879640 returned authors Johansen PB, Hansen KT, Andersen JV, Johansen NL; Xenobiotica 1998 Nov, v28 i11 pp1083-92, DOI field 10.1080/004982598238976. Crossref on that DOI returned first author Johansen, 1998, Xenobiotica, v28 i11 p1083-1092, matching title. The abstract read in full this pass supplies verbatim 'a systemic plasma clearance 5-fold lower than that of GHRP-6', 'Ipamorelin was mainly excreted in the urine, whereas GHRP-6 was predominantly excreted in the bile', '60-80% of the administered dose could be recovered from bile and urine as intact peptide', and 'After intranasal application, the bioavailability of ipamorelin was estimated at approximately 20%. Higher bioavailabilities of approximately 50% were determined for NNC 26-0235, NNC 26-0194 and GHRP-2'.

16. Studied for

    Medicinal chemistry lineage and use as a reference structure

    Ipamorelin was found inside a series of compounds built by removing the central Ala-Trp pair from an older peptide, GHRP-1, as reported in its original characterization paper. It then became the starting structure for a further series aimed at surviving the stomach, built by swapping in a small non-peptide fragment and methylating the backbone; that work produced a four-unit peptide with in-body potency in pigs comparable to ipamorelin, GHRP-2 and GHRP-6, and 10 percent of it reached the bloodstream when given by mouth to dogs. Ipamorelin was also one of the two parent structures for a later hybrid series, tested first in a rat pituitary cell assay and then in pigs. Taken together these papers document its role as a reference scaffold in secretagogue chemistry, not any physiological claim about the compound itself. in cultured rat pituitary cells plus anaesthetised rat, pig and dog studies; structure-activity chemistry Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

    In the literature

    Medicinal chemistry lineage and use as a reference structure

    Ipamorelin was found inside a series of compounds built by removing the central Ala-Trp pair from an older peptide, GHRP-1, as reported in its original characterization paper. It then became the starting structure for a further series aimed at surviving the stomach, built by swapping in a small non-peptide fragment and methylating the backbone; that work produced a four-unit peptide with in-body potency in pigs comparable to ipamorelin, GHRP-2 and GHRP-6, and 10 percent of it reached the bloodstream when given by mouth to dogs. Ipamorelin was also one of the two parent structures for a later hybrid series, tested first in a rat pituitary cell assay and then in pigs. Taken together these papers document its role as a reference scaffold in secretagogue chemistry, not any physiological claim about the compound itself.^{References 4, 17, 18}

    Modelin cultured rat pituitary cells plus anaesthetised rat, pig and dog studies; structure-activity chemistry

    Confidence: moderate

    A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

    Source

    Raun K, Hansen BS, Johansen NL, Thogersen H, Madsen K, Ankersen M, Andersen PH. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-61. DOI: 10.1530/eje.0.1390552. PMID: 9849822 (origin within the series lacking the Ala-Trp dipeptide of GHRP-1). Ankersen M, Johansen NL, Madsen K, Hansen BS, Raun K, Nielsen KK, Thogersen H, Hansen TK, Peschke B, Lau J, Lundt BF, Andersen PH. A new series of highly potent growth hormone-releasing peptides derived from ipamorelin. J Med Chem. 1998 Sep 10;41(19):3699-704. DOI: 10.1021/jm9801962. PMID: 9733495 (the NNC 26-0235 series). Hansen TK, Ankersen M, Raun K, Hansen BS. Highly potent growth hormone secretagogues: hybrids of NN703 and ipamorelin. Bioorg Med Chem Lett. 2001 Jul 23;11(14):1915-8. DOI: 10.1016/s0960-894x(01)00345-6. PMID: 11459660 (the hybrid series).

    PubMed 9849822 PubMed 9733495 PubMed 11459660

    How this citation was checked

    Re-resolved live on 2026-07-28. All three re-resolved this pass. PMID 9849822 efetch and Crossref as recorded in the first area above; its abstract contains verbatim 'ipamorelin was identified within a series of compounds lacking the central dipeptide Ala-Trp of growth hormone-releasing peptide (GHRP)-1', confirming this detail belongs to Raun and not to Ankersen. PubMed efetch of PMID 9733495 returned the full twelve-author Ankersen list above, J Med Chem 1998 Sep, v41 i19 pp3699-704, DOI field 10.1021/jm9801962, and its abstract supplies the 3-(aminomethyl)benzoic acid and backbone N-methylation strategy, the tetrapeptide NNC 26-0235, its comparable in vivo potency to ipamorelin, GHRP-2 and GHRP-6, and verbatim 'NNC 26-0235 demonstrated a 10% oral bioavailability in dogs'; Crossref on that DOI returned first author Ankersen, 1998, Journal of Medicinal Chemistry, v41 i19 p3699-3704. PubMed efetch of PMID 11459660 returned authors Hansen TK, Ankersen M, Raun K, Hansen BS; Bioorg Med Chem Lett 2001 Jul, v11 i14 pp1915-8, DOI field 10.1016/s0960-894x(01)00345-6, with the abstract confirming the lysine-mimetic and naphthyl- or biphenylalanine core series tested in a rat pituitary cell assay and then in pigs; Crossref on that DOI returned first author Hansen, 2001, Bioorganic & Medicinal Chemistry Letters, v11 i14 p1915-1918. The nmol/kg ED50 figure carried by the previous draft for NNC 26-0235, and the nmol/kg screening amount in the Hansen abstract, have both been removed.

17. Studied for

    What happens to growth-hormone-making cells after weeks of exposure

    Young female rats received the peptide, GHRH or saline for 21 days, and afterwards their pituitary cells were grown and examined in the lab. The growth-hormone-making cells looked structurally normal, but the density of secretion granules inside them was higher (P<0.05) after either the peptide or GHRH. In three-day baseline cultures, the proportion of growth-hormone cells and the ratio of strongly to weakly staining cells did not differ between groups, and the baseline amount of hormone held inside the cells over four hours was actually lower in the peptide and GHRH groups than in the saline group. Only in the cells from the rats given the peptide did a further four hours of exposure to the peptide, GHRP-6 or GHRH raise both the proportion of growth-hormone cells and the hormone held inside them. The authors read this as dynamic control over the cell population and its hormone content in the young female rat. Both directions matter: baseline content was lower, and only the re-stimulated content was higher. in rat studies (young female rats given the peptide for 21 days) followed by examination of their cultured pituitary cells Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    What happens to growth-hormone-making cells after weeks of exposure

    Young female rats received the peptide, GHRH or saline for 21 days, and afterwards their pituitary cells were grown and examined in the lab. The growth-hormone-making cells looked structurally normal, but the density of secretion granules inside them was higher (P<0.05) after either the peptide or GHRH. In three-day baseline cultures, the proportion of growth-hormone cells and the ratio of strongly to weakly staining cells did not differ between groups, and the baseline amount of hormone held inside the cells over four hours was actually lower in the peptide and GHRH groups than in the saline group. Only in the cells from the rats given the peptide did a further four hours of exposure to the peptide, GHRP-6 or GHRH raise both the proportion of growth-hormone cells and the hormone held inside them. The authors read this as dynamic control over the cell population and its hormone content in the young female rat. Both directions matter: baseline content was lower, and only the re-stimulated content was higher.^{References 19}

    Modelin rat studies (young female rats given the peptide for 21 days) followed by examination of their cultured pituitary cells

    Confidence: preliminary

    A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Jimenez-Reina L, Canete R, de la Torre MJ, Bernal G. Influence of chronic treatment with the growth hormone secretagogue Ipamorelin, in young female rats: somatotroph response in vitro. Histol Histopathol. 2002;17(3):707-14. DOI: 10.14670/HH-17.707. PMID: 12168778.

    PubMed 12168778

    How this citation was checked

    Re-resolved live on 2026-07-28. PubMed efetch of PMID 12168778 returned authors Jimenez-Reina L, Canete R, de la Torre MJ, Bernal G; Histol Histopathol 2002, v17 i3 pp707-14, DOI field 10.14670/HH-17.707. Crossref has no deposit for that DOI (HTTP 404 on re-check this pass), so it was resolved through doi.org instead: a HEAD request returned HTTP 302 with Location http://www.hh.um.es/Abstracts/Vol_17/17_3/17_3_707.htm, whose path independently confirms volume 17, issue 3, page 707. The abstract read in full this pass supplies the granule volume-density result at P<0.05, the unchanged somatotroph percentage and staining ratio in basal culture, the lower basal intracellular GH content in the Ipamorelin and GHRH groups, and the Ipamorelin-group-only re-stimulation result.

18. Studied for

    Insulin release from isolated pancreas tissue

    Rats were made diabetic with streptozotocin, and four weeks later small pieces of pancreas from those rats and from normal rats were taken out and bathed in the peptide across a range of concentrations, with insulin measured in the bath. In these isolated tissue pieces the peptide significantly increased insulin release from both normal and diabetic pancreas (p<0.04). Blocking calcium channels with diltiazem, or blocking adrenergic receptors with yohimbine or propranolol, or a combination of atropine, propranolol and yohimbine, all significantly reduced that release (p<0.03); atropine on its own reduced it in the diabetic tissue but not the normal tissue. The authors concluded that release runs through calcium channel and adrenergic pathways, and described this as the first study of the compound's effect on pancreatic insulin secretion. This is tissue in a dish, not a whole-body insulin or blood-sugar effect, and it has never been extended to people. in isolated pancreas tissue from normal and streptozotocin-diabetic rats (tissue in a dish, not a live animal) Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Insulin release from isolated pancreas tissue

    Rats were made diabetic with streptozotocin, and four weeks later small pieces of pancreas from those rats and from normal rats were taken out and bathed in the peptide across a range of concentrations, with insulin measured in the bath. In these isolated tissue pieces the peptide significantly increased insulin release from both normal and diabetic pancreas (p<0.04). Blocking calcium channels with diltiazem, or blocking adrenergic receptors with yohimbine or propranolol, or a combination of atropine, propranolol and yohimbine, all significantly reduced that release (p<0.03); atropine on its own reduced it in the diabetic tissue but not the normal tissue. The authors concluded that release runs through calcium channel and adrenergic pathways, and described this as the first study of the compound's effect on pancreatic insulin secretion. This is tissue in a dish, not a whole-body insulin or blood-sugar effect, and it has never been extended to people.^{References 20}

    Modelin isolated pancreas tissue from normal and streptozotocin-diabetic rats (tissue in a dish, not a live animal)

    Confidence: preliminary

    A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Adeghate E, Ponery AS. Mechanism of ipamorelin-evoked insulin release from the pancreas of normal and diabetic rats. Neuro Endocrinol Lett. 2004 Dec;25(6):403-6. PMID: 15665799.

    PubMed 15665799

    How this citation was checked

    Re-resolved live on 2026-07-28. PubMed efetch of PMID 15665799 returned authors Adeghate E, Ponery AS; Neuro Endocrinol Lett 2004 Dec, v25 i6 pp403-6, matching title. The PubMed record carries no DOI field, and none is asserted here. The abstract read in full this pass states verbatim 'pancreatic tissue fragments of normal and diabetic rats were removed and incubated with different concentrations', confirming the tissue-in-a-dish design, and supplies the p<0.04, p<0.03 and p<0.007 values and the full antagonist list. The streptozotocin mg/kg figure in the abstract is deliberately not reproduced.

19. Studied for

    Detection in anti-doping urine testing

    An anti-doping method-development study looked for urinary breakdown products of five growth hormone releasing peptides, including ipamorelin, after nasal administration, with each compound given to a single volunteer and urine collected for two days, then analysed by high-resolution mass spectrometry. The authors reported that hexarelin and ipamorelin broke down heavily and appeared in urine as the parent compound plus a set of fragments, and that one fragment, ipamorelin (1-4) free acid, was still detectable after the parent compound had disappeared entirely, making it the longer-lived analytical target. The paper states that growth hormone releasing peptides are on the World Anti-Doping Agency Prohibited List, and concludes that how long a compound stays detectable depends on the individual's metabolism, the preparation and the route. This is an analytical chemistry result about detectability, with one volunteer per compound; it reports no physiological outcome. in a human analytical method-development study (one volunteer per compound, nasal administration, urine analysis) Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Detection in anti-doping urine testing

    An anti-doping method-development study looked for urinary breakdown products of five growth hormone releasing peptides, including ipamorelin, after nasal administration, with each compound given to a single volunteer and urine collected for two days, then analysed by high-resolution mass spectrometry. The authors reported that hexarelin and ipamorelin broke down heavily and appeared in urine as the parent compound plus a set of fragments, and that one fragment, ipamorelin (1-4) free acid, was still detectable after the parent compound had disappeared entirely, making it the longer-lived analytical target. The paper states that growth hormone releasing peptides are on the World Anti-Doping Agency Prohibited List, and concludes that how long a compound stays detectable depends on the individual's metabolism, the preparation and the route. This is an analytical chemistry result about detectability, with one volunteer per compound; it reports no physiological outcome.^{References 21}

    Modelin a human analytical method-development study (one volunteer per compound, nasal administration, urine analysis)

    Confidence: preliminary

    A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Semenistaya E, Zvereva I, Thomas A, Thevis M, Krotov G, Rodchenkov G. Determination of growth hormone releasing peptides metabolites in human urine after nasal administration of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin. Drug Test Anal. 2015 Oct;7(10):919-25. DOI: 10.1002/dta.1787. PMID: 25869809.

    PubMed 25869809

    How this citation was checked

    Re-resolved live on 2026-07-28. PubMed efetch of PMID 25869809 returned authors Semenistaya E, Zvereva I, Thomas A, Thevis M, Krotov G, Rodchenkov G; Drug Test Anal 2015 Oct, v7 i10 pp919-25, DOI field 10.1002/dta.1787. Crossref on that DOI returned first author Semenistaya, 2015, Drug Testing and Analysis, v7 i10 p919-925, matching title. The abstract read in full this pass states verbatim 'Growth hormone releasing peptides (GHRPs) stimulate secretion of endogenous growth hormone and are listed on the World Anti-Doping Agency (WADA) Prohibited List', 'Each compound was administrated to one volunteer', 'Hexarelin and Ipamorelin metabolized intensively', 'Hexarelin (1-3) free acid and Ipamorelin (1-4) free acid were detected in urine samples after complete withdrawal of parent substances', and the closing sentence on the detection window.

20. Studied for

    A second, larger phase 2 trial with no published results

    Registry record only, included so the human evidence picture is complete. ClinicalTrials.gov NCT01280344, 'Safety and Efficacy of Ipamorelin Compared to Placebo for the Recovery of Gastrointestinal Function', sponsored by Helsinn Therapeutics (U.S.), Inc, is a phase 2 study with 320 people enrolled, comparing ipamorelin against saline. The registry lists it as completed in May 2014 with no results posted. Coverage statement for that absence: a PubMed search for the single term 'ipamorelin' returned 53 records on 2026-07-28, and none of them reports results from this trial. That is a null result on my search, not proof that no report exists anywhere. Nothing about how well or badly the compound worked should be read into this entry in either direction. a human phase 2 clinical trial registry record; no published results located Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    A second, larger phase 2 trial with no published results

    Registry record only, included so the human evidence picture is complete. ClinicalTrials.gov NCT01280344, 'Safety and Efficacy of Ipamorelin Compared to Placebo for the Recovery of Gastrointestinal Function', sponsored by Helsinn Therapeutics (U.S.), Inc, is a phase 2 study with 320 people enrolled, comparing ipamorelin against saline. The registry lists it as completed in May 2014 with no results posted. Coverage statement for that absence: a PubMed search for the single term 'ipamorelin' returned 53 records on 2026-07-28, and none of them reports results from this trial. That is a null result on my search, not proof that no report exists anywhere. Nothing about how well or badly the compound worked should be read into this entry in either direction.^{References 22}

    Modela human phase 2 clinical trial registry record; no published results located

    Confidence: preliminary

    A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    ClinicalTrials.gov Identifier NCT01280344. Safety and Efficacy of Ipamorelin Compared to Placebo for the Recovery of Gastrointestinal Function. Sponsor: Helsinn Therapeutics (U.S.), Inc. Status COMPLETED; phase 2; enrollment 320 (actual); actual completion 2014-05; results posted: none.

    Source

    How this citation was checked

    Re-resolved live on 2026-07-28. Queried the ClinicalTrials.gov v2 REST API directly at https://clinicaltrials.gov/api/v2/studies/NCT01280344, which returned briefTitle exactly as quoted, overallStatus COMPLETED, phases PHASE2, enrollmentInfo count 320 type ACTUAL, interventions Ipamorelin and Saline Solution for Injection, leadSponsor Helsinn Therapeutics (U.S.), Inc, completionDateStruct 2014-05 ACTUAL, and hasResults false. The coverage claim comes from a live PubMed esearch of the term 'ipamorelin' the same day, which returned Count 53.

2 strong / 14 moderate / 4 preliminaryRated by how many independent labs and how many kinds of experiment found the same thing.