IGF-1 DES Research

IGF-1 DES has a defined molecular identity, a described biochemical mechanism, a small animal literature, and no human administration record at all. This article summarizes what the published evidence has investigated, not any outcome to expect.

What IGF-1 DES is

IGF-1 DES is des(1-3)IGF-1: native human insulin-like growth factor 1 with the N-terminal tripeptide Gly-Pro-Glu absent, leaving 67 of the 70 residues.^[1] It is not a purely synthetic construct. The truncated form occurs naturally and has been isolated from bovine colostrum, human brain and porcine uterus.^[1]

Registry numbers circulating for IGF-1 DES return no PubChem compound record, as expected for a protein of this size. Identity is better stated by parent and modification: mature human IGF-1, UniProt P05019, minus Gly-Pro-Glu.

Same receptor, different binding proteins

des(1-3)IGF-1 is not distinguished from IGF-1 by which receptor it engages, because it binds the same type 1 IGF receptor.

What the truncation changes is affinity for the IGF binding proteins that normally sequester circulating IGF-1. Removing the tripeptide removes the glutamate at position 3, which is the residue those binding proteins need. Ballard's review attributes the roughly tenfold potency difference in cultured cells to that loss, and not to a gain at the receptor.^[1] In rat myoblasts, type 1 IGF receptor binding did not fully explain the potency differences, while binding-protein affinity was greatly reduced.^[2] The advantage is conditional on binding proteins being present, and des(1-3)IGF-1 ranked at the top of the potency order in cell lines that secrete them.^[3] In chicken embryo fibroblasts, which secrete no detectable binding proteins, the sibling analogue Long R3 IGF-1 was less potent than IGF-1.^[3] That sibling also binds the type 1 IGF receptor threefold less well than IGF-1 does.^[4]

What has been measured, and in what

Everything below is in vitro or animal work. None of it involves a person.

The tenfold figure is from cell culture, and the same review notes the advantage is only partly retained in vivo.^[1] In rats made catabolic with dexamethasone, des(1-3)IGF-1 was about 2.5-fold more potent than IGF-1 at restoring body weight and nitrogen retention.^[4] That model carries pathologically elevated binding protein 3, the condition that maximizes the analogue's apparent advantage. The authors describe gut as one of the most sensitive IGF-1 target tissues, and there des(1-3)IGF-1 was severalfold more potent than IGF-1.^[5]

The clearest acute effect is on blood glucose. In pigs and marmoset monkeys, the binding-protein-evading variants lowered plasma glucose more potently than IGF-1, and des(1-3)IGF-1 was the most potent tested.^[6] They also suppressed glucose far longer, giving roughly a four- to eightfold increase in the extent of hypoglycemia over four hours.^[6] The endpoint on which des(1-3)IGF-1 ranked most potent is therefore hypoglycemia, not muscle growth. Escaping binding-protein sequestration leaves more free peptide, which is a hypoglycemia and mitogenicity concern rather than a safety feature.

Chronic treatment with the sibling analogue Long R3 IGF-1 reduced growth rate and depressed food intake in 55 kg pigs.^[7] Almost all this in vivo work comes from one Adelaide consortium that commercialized the analogues as reagents, and independent replication is essentially absent. That is an observation from the affiliations on the cited papers, not a published finding.

Human evidence

There is none for this molecule. Ballard's 1996 review stated that clinical opportunities for des(1-3)IGF-1 had not yet been evaluated, and thirty years on that still stands.^[1] There are no registered interventional trials of it, and its human-restricted PubMed record contains no administration to a person.^[8] "No registered interventional trials" is the accurate phrase. It is not the same claim as never studied.

The nearest human evidence belongs to a different molecule. In a 223-patient randomized trial in type 1 diabetes, recombinant human IGF-1 lowered HbA1c and reduced insulin requirement.^[9] Higher exposures were associated with unacceptable levels of adverse events, including edema, jaw pain and early worsening of retinopathy.^[9] That is native rhIGF-1 in patients, and it is not evidence about des(1-3)IGF-1.

Half-life and duration figures

Half-life, duration and "active window" numbers circulate for this compound, and none comes from a human study. No human pharmacokinetic data exist for it, so every such figure is extrapolated from animal or in vitro work, or invented.^[8] The prolonged glucose lowering in pigs and marmosets is a duration of effect in animals, not a plasma half-life, and should not be reported as one.^[6]

What the IGF-1 and cancer literature covers

Large prospective studies link higher circulating IGF-1 to modestly raised risk of prostate and breast cancer.^[10][11] The largest single cohort adds colorectal and thyroid cancer, and reports reduced ovarian and liver risk.^[12]

Those studies measured lifelong endogenous IGF-1 in people who were given nothing, so they are not evidence about des(1-3)IGF-1. No study has shown this compound raises IGF-1 activity in a human, because no study has given it to a human. That literature applies to molecules with demonstrated IGF-1 elevation in people, such as tesamorelin, whose labeling records substantial IGF-1 rises and carries a neoplasm warning.^[13]

The approved molecule in this family is not a credential for this one

Tesamorelin was approved in the United States in 2010 for reduction of excess abdominal fat in adults with HIV-associated lipodystrophy.^[13] It never obtained a European authorization, because the applicant withdrew the application while it was under review by the Committee for Medicinal Products for Human Use.^[14] It was not refused. The committee's provisional view at withdrawal was that the benefits did not outweigh the risks.^[14] GHRP-2 has a reported Japanese approval as a diagnostic agent for growth hormone deficiency testing, unverified from any primary regulatory database.^[15] The source is a 2004 drug profile that recorded the approval as still pending.^[15] A provocative-test approval is not a therapeutic one, and it is not comparable to tesamorelin's.

The approval belongs to the molecule tesamorelin and to one indication. It is not a family credential and must never be written as one. The honest contrast is not that tesamorelin works and the others might too. It is that tesamorelin is the only one of the nine that has been through the process that would let anyone know. IGF-1 DES holds no marketing authorization anywhere, and it does not act at tesamorelin's receptor. Sharing a receptor with an approved medicine names a target rather than a body of evidence.

Limitations and research directions

The identity of purchased material cannot be assumed. A vial sold as IGF-1 Long R3, the sibling analogue, was found on analysis to contain a His6-tagged research construct rather than the labeled molecule.^[16] That is a single case report under a different product name, not a prevalence rate. IGF-1 and its analogues are prohibited under Section S2 of the World Anti-Doping Agency Prohibited List at all times.^[17]

The open questions are basic: no human pharmacokinetic study, no controlled human administration study, no independent replication. IGF-1 DES is supplied for laboratory research use only and is not for human consumption.

Frequently Asked Questions

Does IGF-1 DES act on a different receptor from IGF-1? No. des(1-3)IGF-1 binds the same type 1 IGF receptor that native IGF-1 binds. What the truncation changes is affinity for the IGF binding proteins, and the cause is the loss of the glutamate at position 3.^[1] In rat myoblasts, type 1 IGF receptor binding did not fully explain the potency differences, while binding-protein affinity was greatly reduced.^[2]

Has IGF-1 DES been given to humans? No human administration of des(1-3)IGF-1 is retrievable, and there are no registered interventional trials of it.^[8] Ballard's 1996 review stated that clinical opportunities had not yet been evaluated, and that statement still stands.^[1] The nearest human data belong to recombinant human IGF-1, a different molecule, given in a randomized trial in type 1 diabetes.^[9]

References

1. 1

   Ballard FJ, Wallace JC, Francis GL, Read LC, Tomas FM. Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I. Int J Biochem Cell Biol. 1996. Review. doi:10.1016/1357-2725(96)00056-8. PMID 8930132.
2. 2

   Francis GL, Aplin SE, Milner SJ, McNeil KA, Ballard FJ, Wallace JC. Insulin-like growth factor (IGF)-II binding to IGF-binding proteins and IGF receptors is modified by deletion of the N-terminal hexapeptide or substitution of arginine for glutamate-6 in IGF-II. Biochem J. 1993. doi:10.1042/bj2930713. PMID 7688957.
3. 3

   Francis GL, Ross M, Ballard FJ, et al. Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I indicate the relative importance of IGF-binding protein and receptor binding for enhanced biological potency. J Mol Endocrinol. 1992. doi:10.1677/jme.0.0080213. PMID 1378742.
4. 4

   Tomas FM, Knowles SE, Owens PC, et al. Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats. Biochem J. 1992. doi:10.1042/bj2820091. PMID 1371669.
5. 5

   Read LC, Tomas FM, Howarth GS, et al. Insulin-like growth factor-I and its N-terminal modified analogues induce marked gut growth in dexamethasone-treated rats. J Endocrinol. 1992. doi:10.1677/joe.0.1330421. PMID 1613443.
6. 6

   Tomas FM, Walton PE, Dunshea FR, Ballard FJ. IGF-I variants which bind poorly to IGF-binding proteins show more potent and prolonged hypoglycaemic action than native IGF-I in pigs and marmoset monkeys. J Endocrinol. 1997. doi:10.1677/joe.0.1550377. PMID 9415072.
7. 7

   Walton PE, Dunshea FR, Ballard FJ. In vivo actions of IGF analogues with poor affinities for IGFBPs: metabolic and growth effects in pigs of different ages and GH responsiveness. Prog Growth Factor Res. 1995. Review. doi:10.1016/0955-2235(95)00007-0. PMID 8817682.
8. 8

   Database searches for human administration and registered trials of des(1-3)IGF-1. PubMed E-utilities (des(1-3)IGF-I supplementary concept restricted to Humans[MeSH], and clinical-trial publication types) and ClinicalTrials.gov API v2 (query.intr for des(1-3)IGF-I, returning zero studies). Run 27 August 2026. Anchor citation for the "not yet evaluated" statement: reference 1.
9. 9

   Thrailkill KM, Quattrin T, Baker L, et al (RhIGF-I in IDDM Study Group). Cotherapy with recombinant human insulin-like growth factor I and insulin improves glycemic control in type 1 diabetes. Diabetes Care. 1999. doi:10.2337/diacare.22.4.585. PMID 10189536.
10. 10

    Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004. doi:10.1016/S0140-6736(04)16044-3. PMID 15110491.
11. 11

    Endogenous Hormones and Breast Cancer Collaborative Group (Key TJ, first named author). Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol. 2010. doi:10.1016/S1470-2045(10)70095-4. PMID 20472501.
12. 12

    Knuppel A, Fensom GK, Watts EL, et al. Circulating insulin-like growth factor-I concentrations and risk of 30 cancers: prospective analyses in UK Biobank. Cancer Res. 2020. doi:10.1158/0008-5472.CAN-20-1281. PMID 32709735.
13. 13

    US Food and Drug Administration. Regulatory record and approved prescribing information for tesamorelin (original approval 10 November 2010; labeling current 2026). Retrieved from Drugs@FDA and the openFDA drug label endpoint, 27 August 2026.
14. 14

    European Medicines Agency, Committee for Medicinal Products for Human Use. Withdrawn marketing authorisation application for tesamorelin; application submitted by Ferrer Internacional S.A. and withdrawn by the applicant on 21 June 2012, at which time the committee's provisional opinion was that the benefits did not outweigh the risks. EMA withdrawn-applications record.
15. 15

    Adis drug profile, no named author. Pralmorelin: GHRP 2, GPA 748, growth hormone-releasing peptide 2, KP-102 D, KP-102 LN, KP-102D, KP-102LN. Drugs R D. 2004. Review. doi:10.2165/00126839-200405040-00011. PMID 15230633. The profile records KP-102D as awaiting approval in Japan as a diagnostic agent for hypothalamo-pituitary function.
16. 16

    Kohler M, Thomas A, Walpurgis K, Terlouw K, Schaenzer W, Thevis M. Detection of His-tagged Long-R3-IGF-I in a black market product. Growth Horm IGF Res. 2010. doi:10.1016/j.ghir.2010.07.001. PMID 20675162.
17. 17

    World Anti-Doping Agency. The 2026 Prohibited List, International Standard, Section S2 (Peptide Hormones, Growth Factors, Related Substances, and Mimetics). In force 1 January 2026.