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CJC-1295 vs Sermorelin vs Ipamorelin vs Tesamorelin — Growth Hormone Peptide Comparison

CJC-1295, Sermorelin, Ipamorelin, and Tesamorelin are four growth-hormone-axis peptides. Tesamorelin is the group's only FDA-approved member (Egrifta, BLA022505, approved 2010). No combination or head-to-head trial of all four exists. This page reports each compound's evidence from its own separate trial, and flags where the trial's route of administration or approval status differs from what typical research protocols or marketing claims describe.

On this page
  1. 1.Molecule Identity
  2. 2.Human Evidence, by Molecule
  3. 3.Route Discrepancies
  4. 4.Evidence Level
  5. 5.FAQ
  6. 6.References

Molecule Identity

CJC-1295, Sermorelin, and Tesamorelin are all GHRH (growth hormone-releasing hormone) analogs, activating the GHRH receptor on pituitary somatotroph cells. Ipamorelin is a GHRP (growth hormone-releasing peptide) that activates a separate receptor, GHS-R1a — the same receptor ghrelin uses. CJC-1295 exists in two distinct forms not interchangeable in the evidence below: CJC-1295 with DAC (a chemical modification that binds it to serum albumin) and CJC-1295 without DAC (also called Modified GRF 1-29). Tesamorelin is GHRH(1-44) carrying a stabilizing N-terminal trans-3-hexenoic acid modification that resists DPP-IV degradation — a different stabilization strategy from CJC-1295's DAC, and the only one of the four with FDA approval.

CJC-1295SermorelinIpamorelinTesamorelin
ClassGHRH analogGHRH analog (native GHRH(1-29) sequence)GHRP (ghrelin-receptor agonist)GHRH analog (GHRH(1-44) with a stabilizing N-terminal modification)
ReceptorGHRH receptorGHRH receptorGHS-R1aGHRH receptor
Cited human trialTeichman et al. 2006 (PMID 16352683) — DAC form onlyKhorram et al. 1997 (PMID 9141536, a related analog) and Chen et al. 1993 (PMID 8329830, sermorelin itself)Gobburu et al. 1999 (PMID 10496658) and Beck et al. 2014 (PMID 25331030)Falutz et al. 2010 (PMID 20554713) — pooled analysis of two Phase 3 RCTs, N=806
Route testedSubcutaneousSubcutaneousIntravenous (both cited trials)Subcutaneous — same route as the FDA-approved product
Half-life (as measured)5.8–8.1 days (DAC form; Teichman et al. 2006)~10–20 minutes (short-acting GHRH class)~2 hours (Gobburu et al. 1999)8–11 minutes (per Egrifta SV / Egrifta WR prescribing information)
No-DAC / SC form tested in humans?No human study of CJC-1295 without DAC (Modified GRF 1-29) was identifiedN/A — sermorelin has no DAC variantNo human study of subcutaneous ipamorelin was identifiedN/A — no DAC variant; the trialed form is the FDA-approved form
FDA approval statusNot FDA-approvedNot FDA-approvedNot FDA-approvedFDA-approved (BLA022505, Theratechnologies) since November 10, 2010 — Egrifta, now Egrifta SV / Egrifta WR, for reduction of excess abdominal fat in HIV-associated lipodystrophy

Each row draws on a different trial, in a different population, and in two cases (CJC-1295, Ipamorelin) a route of administration different from the subcutaneous route research protocols typically describe. Tesamorelin's cited trial used the same subcutaneous route and dose form as the approved product. No cell in this table should be read as directly comparable to another without checking the source study.

Human Evidence, by Molecule

CJC-1295. Teichman et al. 2006 (J Clin Endocrinol Metab, PMID 16352683) gave CJC-1295 with DAC subcutaneously to 35 healthy adults (ages 21–61) across two randomized, placebo-controlled, double-blind trials (28-day single-ascending-dose and 49-day repeated-dose designs), against 7 placebo subjects. A single dose produced a 2- to 10-fold rise in plasma growth hormone lasting 6+ days and a 1.5- to 3-fold rise in IGF-1 lasting 9–11 days, with an estimated half-life of 5.8–8.1 days. This trial tested the DAC form only. No published human study of CJC-1295 without DAC was identified.

Sermorelin. Chen et al. 1993 (Acta Paediatr Suppl, PMID 8329830) randomized 60 children with hypothalamic growth hormone deficiency to sermorelin (GHRH(1-29)-NH2, 30 or 60 mcg/kg/day subcutaneously) or growth hormone for 6 months; growth was significantly better with GH than with either sermorelin dose, and the two sermorelin-dose groups did not differ from each other. Khorram et al. 1997 (J Clin Endocrinol Metab, PMID 9141536) is frequently cited alongside sermorelin but tested [Nle27]GHRH(1-29)-NH2 — a related analog with one amino acid substituted from native sermorelin, not sermorelin itself — in 19 adults ages 55–71, subcutaneously, nightly for 16 weeks; IGF-1 and IGFBP-3 rose within 2 weeks, and lean body mass increased by the 16-week endpoint in men but not women.

Ipamorelin. Gobburu et al. 1999 (Pharm Res, PMID 10496658) tested ipamorelin in 40 healthy male volunteers using five ascending doses (4.21–140.45 nmol/kg, roughly 3–100 mcg/kg) given as a 15-minute intravenous infusion — not subcutaneous. Growth hormone release was dose-dependent, peaking at 40 minutes and returning to baseline within a few hours, consistent with the trial's measured 2-hour terminal half-life. Beck et al. 2014 (Int J Colorectal Dis, PMID 25331030, NCT00672074) gave intravenous ipamorelin at 0.03 mg/kg twice daily for up to 7 days to 114 postoperative bowel-resection patients — also intravenous, and in a surgical-recovery population rather than healthy volunteers. No human study of subcutaneous ipamorelin was identified.

Tesamorelin. Falutz et al. 2010 (J Clin Endocrinol Metab, PMID 20554713) is a pooled analysis of two multicenter, double-blind, placebo-controlled Phase 3 trials in 806 HIV-infected patients with excess abdominal fat, randomized 2:1 to tesamorelin 2 mg or placebo, subcutaneously, once daily. At week 26, visceral adipose tissue (VAT) decreased significantly versus placebo (treatment effect −15.4%, P<0.001), triglycerides fell (treatment effect −12.3%, P<0.001), and IGF-1 rose (108 vs −7 ng/mL, P<0.001). In a 26-week safety extension, patients continuing tesamorelin maintained the VAT reduction through week 52 (−17.5%). This is the strongest human evidence base of the four compounds on this page — two large Phase 3 RCTs that led to FDA approval — but it was conducted in HIV-associated lipodystrophy, not in the healthy or age-advanced populations the other three trials studied, and it measured visceral fat and lipids rather than the GH/IGF-1 pulsatility endpoints emphasized for the other compounds.

Route Discrepancies

Two of the four compounds have a route gap between what was studied in humans and what research protocols typically describe. CJC-1295's only human trial tested the DAC form (subcutaneous, but chemically distinct from the no-DAC form most stack protocols reference); no human trial of CJC-1295 without DAC exists. Ipamorelin's only two human trials both used intravenous infusion; no human trial of the subcutaneous route research protocols typically describe has been identified. Sermorelin's own trial (Chen et al. 1993) did use the subcutaneous route, but its supporting adult-population data (Khorram et al. 1997) tested a related-but-not-identical analog. Tesamorelin is the exception: Falutz et al. 2010 tested it subcutaneously at 2 mg once daily, the same route and dose form later approved as Egrifta — no gap between the trialed route and the labeled product, though current formulations (Egrifta SV at 1.4 mg, Egrifta WR at 1.28 mg) use lower daily doses than the 2 mg tested in this trial.

Adverse events reported in the same trials

Teichman et al. 2006 reported CJC-1295 DAC was safe and well tolerated at 30–60 mcg/kg, including one Phase 2 subject death the attending physician attributed to unrelated coronary artery disease. Chen et al. 1993 did not report a between-arm difference in adverse events for sermorelin vs GH. Gobburu et al. 1999 reported no adverse events beyond the expected transient GH/IGF-1 rise. Beck et al. 2014 reported a treatment-emergent adverse event in 87.5% of the ipamorelin group versus 94.8% of the placebo group, concluding the dose was well tolerated over up to 7 days. Falutz et al. 2010 reported tesamorelin was generally well tolerated with no clinically meaningful differences in glucose parameters versus placebo; the tesamorelin profile page reports injection-site reactions, arthralgia (joint pain), and peripheral edema as the most-reported effects from the completed Phase 3 program and post-marketing surveillance, with anti-tesamorelin IgG antibodies detected in 50% of patients at 26 weeks and 47% at 52 weeks (85% in those with hypersensitivity reactions), and similar visceral-fat reductions with or without them, per the Egrifta label.

Evidence Level

CJC-1295: Human RCT for the DAC form only (Teichman et al. 2006, PMID 16352683) — no human trial of the no-DAC form exists. Sermorelin: Human RCT (Chen et al. 1993, PMID 8329830) — in children with GH deficiency, where GH produced significantly faster growth than GHRH(1-29); adult data on sermorelin itself are small and uncontrolled (Vittone et al. 1997, n=11, no placebo), alongside a related-but-not-identical GHRH analog (Khorram et al. 1997, PMID 9141536). Ipamorelin: Human RCT but IV only (Gobburu et al. 1999, PMID 10496658; Beck et al. 2014, PMID 25331030, which missed its primary endpoint: 25.3 vs 32.6 hours to first tolerated meal, p=0.15) — a second Phase 2 trial (NCT01280344, n=320) completed with no results posted, and no human trial of subcutaneous administration exists. Tesamorelin: Human RCT, the largest and most robust of the four (Falutz et al. 2010, PMID 20554713, N=806 pooled across two Phase 3 trials) — the evidence base that supports its FDA approval, though specific to HIV-associated lipodystrophy rather than the general research uses discussed for the other three. Full profiles, including each compound's wider citation list, are on the CJC-1295, Sermorelin, Ipamorelin, and Tesamorelin profile pages.

FAQ

Has a trial ever compared CJC-1295, Sermorelin, and Ipamorelin against each other?

No. No combination or head-to-head human trial of these three compounds was identified. Each compound's evidence below comes from its own separate trial, in a different population, using a different route of administration in some cases.

Does the CJC-1295 human trial apply to the no-DAC form commonly used in research protocols?

No. Teichman et al. 2006 (PMID 16352683) tested CJC-1295 with DAC (drug affinity complex), the long-acting, albumin-binding form, in 35 healthy adults. No published human study of CJC-1295 without DAC (Modified GRF 1-29) was identified. Community-reported dosing for the no-DAC form is reported practice, not trial-derived.

Was ipamorelin's human trial subcutaneous, matching how research protocols use it?

No. Both cited human trials of ipamorelin used intravenous administration — Gobburu et al. 1999 (PMID 10496658) gave a 15-minute IV infusion in healthy volunteers, and Beck et al. 2014 (PMID 25331030) gave twice-daily IV dosing in postoperative bowel-resection patients. No human study of subcutaneous ipamorelin was identified. Community-reported subcutaneous dosing figures diverge from both trials in route (subcutaneous vs intravenous) and dose basis (a flat mcg figure vs the trials' own weight-based dosing).

Is the sermorelin trial evidence specific to sermorelin itself?

Partly. Khorram et al. 1997 (PMID 9141536) tested [Nle27]GHRH(1-29)-NH2, a related GHRH analog with one amino acid substituted from native sermorelin — not identical to sermorelin. Chen et al. 1993 (PMID 8329830) is a human RCT of sermorelin itself (GHRH(1-29)-NH2, 30 or 60 mcg/kg/day) in 60 children with hypothalamic growth hormone deficiency; that trial found growth was significantly better with GH than with either sermorelin dose, and the two sermorelin-dose groups did not differ from each other.

Did the ipamorelin trials show a benefit?

Gobburu et al. 1999 found ipamorelin produced a dose-dependent rise in growth hormone in healthy volunteers via IV infusion. Beck et al. 2014, a Phase 2 trial in postoperative bowel-resection patients, found no significant difference from placebo on its efficacy endpoint (time to tolerating a solid meal), though the drug was reported as well tolerated.

Is tesamorelin different from the other three compounds on this page?

Yes, in evidence base and regulatory status. Tesamorelin is FDA-approved (BLA022505, Theratechnologies, since November 10, 2010) as Egrifta, now sold as Egrifta SV and Egrifta WR, for reduction of excess abdominal fat in HIV-associated lipodystrophy — the only one of the four compounds on this page with any FDA approval. That approval rests on Falutz et al. 2010 (PMID 20554713), a pooled analysis of two Phase 3 randomized, double-blind, placebo-controlled trials in 806 patients, versus the smaller pharmacology and proof-of-concept trials cited for CJC-1295, sermorelin, and ipamorelin. No trial has compared tesamorelin against any of the other three.

References

  1. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799-805. https://pubmed.ncbi.nlm.nih.gov/16352683/
  2. Chen RG, Shen YN, Yei J, et al. A comparative study of growth hormone (GH) and GH-releasing hormone(1-29)-NH2 for stimulation of growth in children with GH deficiency. Acta Paediatr Suppl. 1993;388:32-35; discussion 36. https://pubmed.ncbi.nlm.nih.gov/8329830/
  3. Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab. 1997;82(5):1472-1479. https://pubmed.ncbi.nlm.nih.gov/9141536/
  4. Gobburu JV, Agersø H, Jusko WJ, Ynddal L. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharm Res. 1999;16(9):1412-1416. https://pubmed.ncbi.nlm.nih.gov/10496658/
  5. 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;29(12):1527-1534. NCT00672074. https://pubmed.ncbi.nlm.nih.gov/25331030/
  6. Falutz J, Mamputu JC, Potvin D, et al. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. 2010;95(9):4291-4304. https://pubmed.ncbi.nlm.nih.gov/20554713/
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