IGF-1 DES

updated

IGF-1 DES, or des(1-3)IGF-1, is a naturally occurring N-terminal truncation of IGF-1 with much reduced binding to IGF-binding proteins. No controlled human study exists: the records reviewed hold no human dose, pharmacokinetics or safety data, and nothing on tendon or ligament repair by any route. The closest muscle result is a 7-day infusion in diabetic rats, and transgenic mice overexpressing it in mammary tissue developed mammary adenocarcinomas at 53% by 23 months.

Truncated insulin-like growth factor 1 (IGF-1) variant

  • Des(1-3)IGF-I lacks the N-terminal tripeptide Gly-Pro-Glu and is a separate molecule from IGF-1 LR3; PubChem returned no compound record for it on 9 October 2026.
  • It is generally about 10-fold more potent than IGF-I at stimulating hypertrophy and proliferation of cultured cells, because it binds IGF-binding proteins much less.
  • In rats given intravenous labeled tracers, mean total plasma clearance was 4.59 ml/min per kg for des(1-3)IGF-I versus 1.20 for IGF-I, so it was cleared roughly four times faster than intact IGF-I.
  • In streptozotocin-induced diabetic rats infused for 7 days, des(1-3)IGF-I at 1.08 mg/kg per day produced effects on body weight and nitrogen retention approximately 70% of those of insulin.
  • In transgenic mice overexpressing des(1-3)hIGF-I in mammary tissue, 53% developed mammary adenocarcinomas by 23 months of age; this is lifetime tissue overexpression, not an injected dose.
  • An antidoping laboratory states that des(1-3)-IGF-I is prohibited in sport, was never approved for use in humans, and is sold as a black market product, and found abundant signs of lower quality, oxidized peptide forms in those products.

What is des(1-3)IGF-1, and is it approved for anything?

Des(1-3)IGF-I is a naturally occurring N-terminal truncation of IGF-I that lacks Gly-Pro-Glu and is a separate molecule from IGF-1 LR3. No approval for it appears in the records reviewed, and an antidoping laboratory states it was never approved for use in humans.

Des(1-3)IGF-I is a truncated variant of human IGF-I with the tripeptide Gly-Pro-Glu absent from the N-terminus. It has been isolated from bovine colostrum, human brain and porcine uterus and probably results from post-translational cleavage of IGF-I, so it is a naturally occurring fragment rather than an engineered construct.

It is a different molecule from IGF-1 LR3. IGF-1 LR3 adds a 13-residue N-terminal extension and substitutes position 3, and the two are separate molecules with separate records.

PubChem returned no compound record on 9 October 2026 for des(1-3)IGF-I, DES(1-3)IGF1, IGF-1 DES or Insulin-Like Growth Factor I (4-70), human, so no formula, molecular weight or CAS number is printed here.

No approval for des(1-3)IGF-I appears in the records reviewed. An antidoping laboratory paper states that IGF-I and its analogs LongR3-IGF-I, Des(1-3)-IGF-I and R3-IGF-I are prohibited substances in sport, were never approved for use in humans, and are readily available as black market products for bodybuilding. A 1996 review of des(1-3)IGF-I states that clinical opportunities had not yet been evaluated.

1996 review: naturally occurring N-terminal truncation, about 10-fold more potent in cells

Narrative review

Ballard FJ et al. Int J Biochem Cell Biol. 1996;28(10):1085-7. PMID 8930132.

Des(1-3)IGF-I is a truncated variant of human IGF-I with the tripeptide Gly-Pro-Glu absent from the N-terminus. It has been isolated from bovine colostrum, human brain and porcine uterus, and probably results from post-translational cleavage of IGF-I, so it is a naturally occurring fragment rather than an engineered construct. It is generally about 10-fold more potent than IGF-I at stimulating hypertrophy and proliferation of cultured cells, a consequence of much reduced binding to IGF-binding proteins caused by the absence of the glutamate at position 3. The review states that clinical opportunities for des(1-3)IGF-I had not yet been evaluated. PubChem returned no compound record on 9 October 2026 for des(1-3)IGF-I, DES(1-3)IGF1, IGF-1 DES or Insulin-Like Growth Factor I (4-70), human.

Participants / model
Chemical identity, not a clinical population
Treatment
Truncated IGF-I variant
Follow-up
Not applicable
Study design
Review of original reports
Funding
not stated in the source

IGF-1 LR3 is a different modification: it adds a 13-residue N-terminal extension and substitutes position 3. The two are separate molecules with separate records.

Read the original source
Antidoping analysis: black market product quality, rat intramuscular detection window

Animal study

Mongongu C et al. Drug Test Anal. 2021;13(7):1256-1269. PMID 33587816.

An antidoping laboratory validating a detection method states that IGF-I and its analogs LongR3-IGF-I, Des(1-3)-IGF-I and R3-IGF-I are prohibited substances in sport, were never approved for use in humans, and are readily available as black market products for bodybuilding. Analysing those black market products, the authors found abundant signs of lower quality, oxidized peptide forms, which is why their method monitors both the native and the mono-oxidized forms. After a single intramuscular administration at 100 micrograms/kg in rats, unchanged Des(1-3)-IGF-I and R3-IGF-I were detected until 24 hours after administration, while LongR3-IGF-I disappeared rapidly after 4 hours. The same degradation products appeared after in vitro incubation in human whole blood.

Participants / model
Black market product samples; rats for the administration study; human serum and whole blood for method work
Treatment
Intramuscular administration in rats; product analysis
Follow-up
Detection followed to 24 hours after administration
Study design
Original analytical study
Funding
not stated in the source

This is the one laboratory that analysed market product, and it reports quality problems. The rat result describes a detection window, not a benefit.

Read the original source

What does the approved IGF-1 drug show, and does it apply here?

INCRELEX is recombinant full-length human IGF-1 approved for pediatric growth failure, with a contraindication in pediatric patients with malignant neoplasia or a history of malignancy and warnings for severe hypoglycemia and malignant neoplasia. It is a different molecule from the truncated variant, and nothing on its label transfers except as context.

INCRELEX (mecasermin) is recombinant human IGF-1, 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 Da. It was approved under BLA 021839 on 30 August 2005 for growth failure in pediatric patients 2 years and older with severe primary IGF-1 deficiency or with growth hormone gene deletion who have developed neutralizing antibodies to growth hormone. The label version used here took effect on 5 August 2025.

The label contraindicates use in patients with closed epiphyses and in pediatric patients with malignant neoplasia or a history of malignancy. Warnings include severe hypoglycemia leading to hypoglycemic seizures, because it has insulin-like hypoglycemic effects, anaphylaxis requiring hospitalization, and several observed cases of malignant neoplasia in treated pediatric patients, with instruction to discontinue if evidence of malignant neoplasia develops.

This is the full-length molecule, not the truncated variant, and the indication is pediatric growth failure, not muscle growth in adults. It is context for what an approved IGF-1 looks like, not evidence about des(1-3)IGF-I.

INCRELEX label, version effective 5 August 2025: full-length IGF-1, pediatric indication, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INCRELEX (mecasermin) solution for subcutaneous injection, prescribing information, label version effective 5 August 2025. Set ID a8b27a1b-a611-4f91-ad22-76d4b390c3ae.

INCRELEX (mecasermin) is recombinant human IGF-1, 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 Da. It was approved under BLA 021839 on 30 August 2005 for growth failure in pediatric patients 2 years and older with severe primary IGF-1 deficiency or with growth hormone gene deletion who have developed neutralizing antibodies to growth hormone. It is contraindicated in patients with closed epiphyses and in pediatric patients with malignant neoplasia or a history of malignancy. Warnings include severe hypoglycemia leading to hypoglycemic seizures, because it has insulin-like hypoglycemic effects, anaphylaxis requiring hospitalization, and several observed cases of malignant neoplasia in treated pediatric patients, with instruction to discontinue if evidence of malignant neoplasia develops.

Participants / model
Pediatric patients 2 years and older with severe primary IGF-1 deficiency or growth hormone gene deletion with neutralizing antibodies to growth hormone
Treatment
INCRELEX solution for subcutaneous injection
Follow-up
Label version effective 5 August 2025
Study design
FDA prescribing information
Funding
not stated in the source

This is the full-length molecule, not the truncated variant, and the indication is pediatric growth failure, not muscle growth in adults. Nothing on it transfers to des(1-3)IGF-I except as context.

Read the original source

What have rat studies shown?

In rats, des(1-3)IGF-I was cleared about four times faster than intact IGF-I after intravenous tracer doses, and a 7-day infusion in diabetic rats produced effects on nitrogen retention about 70% of insulin's. No human study of any kind exists.

After intravenous injection of labeled tracers into rats, most des(1-3)IGF-I radioactivity remained free rather than associating with binding proteins. Mean total plasma clearances were 4.59 ml/min per kg for des(1-3)IGF-I, 1.20 for IGF-I and 1.34 for IGF-II, so the truncated variant was cleared roughly four times faster than intact IGF-I. Mean steady-state volume of distribution was 461 ml/kg for des(1-3)IGF-I versus 167 and 181 for IGF-I and IGF-II, and radioactivity appeared in the kidneys more than in other organs. These are rat numbers from intravenous tracer doses.

The closest thing to a muscle result is in sick rats, by infusion. In streptozotocin-induced diabetic rats infused for 7 days, des(1-3)IGF-I at 1.08 mg/kg per day produced effects on body weight and nitrogen retention approximately 70% of those obtained with 25 or 30 units of insulin per kg per day, while IGF-I at 1.05 or 1.08 mg/kg per day produced about 30% and human growth hormone at 1.38 mg/kg per day was not effective. The improvements in nitrogen balance were accounted for in part by increases in muscle protein synthesis. Muscle protein breakdown, assessed by 3-methylhistidine excretion, was inhibited by insulin but not by the IGF peptides, and carcass fat increased substantially with insulin but not with the IGF peptides.

After a single intramuscular administration at 100 micrograms/kg in rats, unchanged Des(1-3)-IGF-I and R3-IGF-I were detected until 24 hours after administration, while LongR3-IGF-I disappeared rapidly after 4 hours. This was an antidoping detection study, so the result describes a detection window and not a benefit.

All three are rat studies. No human pharmacokinetic study exists for this molecule in the records reviewed.

Rat pharmacokinetics: cleared about four times faster than IGF-I

Animal study

Ballard FJ et al. J Endocrinol. 1991;128(2):197-204. PMID 2005410.

After intravenous injection of labeled tracers into rats, most des(1-3)IGF-I radioactivity remained free rather than associating with binding proteins. Mean total plasma clearances were 4.59 ml/min per kg for des(1-3)IGF-I, 1.20 for IGF-I and 1.34 for IGF-II, so the truncated variant was cleared roughly four times faster than intact IGF-I. Mean steady-state volume of distribution was 461 ml/kg for des(1-3)IGF-I versus 167 and 181 for IGF-I and IGF-II. Radioactivity appeared in the kidneys more than in other organs for all three tracers.

Participants / model
Rats
Treatment
Intravenous labeled tracer
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

These are rat numbers from intravenous tracer doses. No human pharmacokinetic study exists for this molecule in the records reviewed.

Read the original source
Diabetic rats: 7-day infusion, nitrogen retention about 70% of insulin's effect

Animal study

Tomas FM et al. Biochem J. 1991;276 ( Pt 2)(Pt 2):547-54. PMID 1710892.

In streptozotocin-induced diabetic rats infused for 7 days, des(1-3)IGF-I at 1.08 mg/kg per day produced effects on body weight and nitrogen retention that were approximately 70% of those obtained with 25 or 30 units of insulin per kg per day, while IGF-I at 1.05 or 1.08 mg/kg per day produced about 30% and human growth hormone at 1.38 mg/kg per day was not effective. The improvements in nitrogen balance were accounted for in part by increases in muscle protein synthesis. Muscle protein breakdown, assessed by 3-methylhistidine excretion, was inhibited by insulin but not by the IGF peptides, and carcass fat increased substantially with insulin but not with the IGF peptides.

Participants / model
Streptozotocin-induced diabetic rats
Treatment
Continuous infusion of des(1-3)IGF-I, IGF-I, human growth hormone or insulin
Follow-up
7 days
Study design
Original preclinical study with active comparators
Funding
not stated in the source

This is systemic infusion in diabetic rats, not a site-specific injection in a trained person.

Read the original source
Antidoping analysis: black market product quality, rat intramuscular detection window

Animal study

Mongongu C et al. Drug Test Anal. 2021;13(7):1256-1269. PMID 33587816.

An antidoping laboratory validating a detection method states that IGF-I and its analogs LongR3-IGF-I, Des(1-3)-IGF-I and R3-IGF-I are prohibited substances in sport, were never approved for use in humans, and are readily available as black market products for bodybuilding. Analysing those black market products, the authors found abundant signs of lower quality, oxidized peptide forms, which is why their method monitors both the native and the mono-oxidized forms. After a single intramuscular administration at 100 micrograms/kg in rats, unchanged Des(1-3)-IGF-I and R3-IGF-I were detected until 24 hours after administration, while LongR3-IGF-I disappeared rapidly after 4 hours. The same degradation products appeared after in vitro incubation in human whole blood.

Participants / model
Black market product samples; rats for the administration study; human serum and whole blood for method work
Treatment
Intramuscular administration in rats; product analysis
Follow-up
Detection followed to 24 hours after administration
Study design
Original analytical study
Funding
not stated in the source

This is the one laboratory that analysed market product, and it reports quality problems. The rat result describes a detection window, not a benefit.

Read the original source

Does des(1-3)IGF-1 repair tendon, ligament or muscle?

No study supports it. The muscle result is continuous infusion in diabetic rats, site-specific injection has not been studied, and tendon and ligament repair has no study by any route. PubMed searches on 9 October 2026 found no human administration study.

Sellers describe site-specific injections for lagging muscle growth and faster tendon, ligament and muscle repair, used alongside BPC-157 and TB-500.

The muscle claim rests on continuous systemic infusion in diabetic rats. Site-specific injection has never been studied for this molecule in the records reviewed, tendon and ligament repair has no study at all, and no study combined des(1-3)IGF-I with BPC-157 or TB-500.

A PubMed search on 9 October 2026 for des(1-3)IGF-I or des(1-3)IGF-1 with tendon, ligament, muscle injury or resistance exercise returned 4 records, whose titles cover mechano growth factor expression in E. coli, IGF-I cardioprotection, cell culture as a tool for nutritional disease therapies, and IGFs as putative trophic agents for motoneuron survival. None names a tendon or ligament experiment.

The same terms restricted to the humans MeSH term with clinical trial, healthy volunteers or administration returned 9 records: two antidoping analytical methods, human neutrophil and neuroblastoma cell work, endometrial cancer cell receptor modulation, rat studies and a mammary gland development study. None is a human administration study. A broader search on the compound names returned 198 records of cell, rat and analytical work.

Diabetic rats: 7-day infusion, nitrogen retention about 70% of insulin's effect

Animal study

Tomas FM et al. Biochem J. 1991;276 ( Pt 2)(Pt 2):547-54. PMID 1710892.

In streptozotocin-induced diabetic rats infused for 7 days, des(1-3)IGF-I at 1.08 mg/kg per day produced effects on body weight and nitrogen retention that were approximately 70% of those obtained with 25 or 30 units of insulin per kg per day, while IGF-I at 1.05 or 1.08 mg/kg per day produced about 30% and human growth hormone at 1.38 mg/kg per day was not effective. The improvements in nitrogen balance were accounted for in part by increases in muscle protein synthesis. Muscle protein breakdown, assessed by 3-methylhistidine excretion, was inhibited by insulin but not by the IGF peptides, and carcass fat increased substantially with insulin but not with the IGF peptides.

Participants / model
Streptozotocin-induced diabetic rats
Treatment
Continuous infusion of des(1-3)IGF-I, IGF-I, human growth hormone or insulin
Follow-up
7 days
Study design
Original preclinical study with active comparators
Funding
not stated in the source

This is systemic infusion in diabetic rats, not a site-specific injection in a trained person.

Read the original source
Searches, 9 October 2026: no tendon or ligament study, no human administration study

PubMed search record

PubMed search run on 9 October 2026: (des(1-3)IGF-I OR des(1-3)IGF-1) AND (tendon OR ligament OR muscle injury OR resistance exercise), 4 records. A second search for the same terms restricted to the humans MeSH term with clinical trial, healthy volunteers or administration, 9 records. A broader search on the compound names, 198 records.

The search for des(1-3)IGF-I or des(1-3)IGF-1 with tendon, ligament, muscle injury or resistance exercise returned 4 records, with titles covering expression of mechano growth factor in E. coli, IGF-I cardioprotection in myocardial ischemia and reperfusion, cell culture as a tool for identifying nutritional disease therapies, and IGFs as putative muscle-derived trophic agents for motoneuron survival; none names a tendon or ligament experiment. The same terms restricted to the humans MeSH term with clinical trial, healthy volunteers or administration returned 9 records, with titles covering two antidoping analytical methods, human neutrophil and neuroblastoma cell work, endometrial cancer cell receptor modulation, rat studies and a mammary gland development study; none is a human administration study. A broader search on the compound names returned 198 records, which are cell, rat and analytical work. The records reviewed contain no human dose, no human pharmacokinetics, no human safety data, no trial and no study of tendon or ligament repair by any route.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source

What do analyses of market product and sport rules show?

An antidoping laboratory found abundant lower-quality, oxidized peptide forms in black market products, and states that des(1-3)-IGF-I is prohibited in sport and was never approved for use in humans.

An antidoping laboratory validating a detection method states that IGF-I and its analogs LongR3-IGF-I, Des(1-3)-IGF-I and R3-IGF-I are prohibited substances in sport, were never approved for use in humans, and are readily available as black market products for bodybuilding.

Analysing those black market products, the authors found abundant signs of lower quality, oxidized peptide forms, which is why their method monitors both the native and the mono-oxidized forms. The same degradation products appeared after in vitro incubation in human whole blood.

This is the one laboratory in the records reviewed that analysed market product.

Antidoping analysis: black market product quality, rat intramuscular detection window

Animal study

Mongongu C et al. Drug Test Anal. 2021;13(7):1256-1269. PMID 33587816.

An antidoping laboratory validating a detection method states that IGF-I and its analogs LongR3-IGF-I, Des(1-3)-IGF-I and R3-IGF-I are prohibited substances in sport, were never approved for use in humans, and are readily available as black market products for bodybuilding. Analysing those black market products, the authors found abundant signs of lower quality, oxidized peptide forms, which is why their method monitors both the native and the mono-oxidized forms. After a single intramuscular administration at 100 micrograms/kg in rats, unchanged Des(1-3)-IGF-I and R3-IGF-I were detected until 24 hours after administration, while LongR3-IGF-I disappeared rapidly after 4 hours. The same degradation products appeared after in vitro incubation in human whole blood.

Participants / model
Black market product samples; rats for the administration study; human serum and whole blood for method work
Treatment
Intramuscular administration in rats; product analysis
Follow-up
Detection followed to 24 hours after administration
Study design
Original analytical study
Funding
not stated in the source

This is the one laboratory that analysed market product, and it reports quality problems. The rat result describes a detection window, not a benefit.

Read the original source

How does des(1-3)IGF-1 work, and how fast is it cleared?

Des(1-3)IGF-I lacks the glutamate at position 3 and binds IGF-binding proteins much less, which makes it about 10-fold more potent than IGF-I in cultured cells. In rats it was cleared about four times faster than intact IGF-I.

The absence of the glutamate at position 3 causes much reduced binding to IGF-binding proteins, and des(1-3)IGF-I is generally about 10-fold more potent than IGF-I at stimulating hypertrophy and proliferation of cultured cells.

In rats, most des(1-3)IGF-I radioactivity remained free rather than associating with binding proteins after intravenous tracer doses, and plasma clearance was 4.59 ml/min per kg versus 1.20 for IGF-I, about four times faster. The truncation that raises potency in cells therefore shortens exposure in rats rather than lengthening it.

In diabetic rats infused for 7 days, des(1-3)IGF-I improved nitrogen balance in part by increasing muscle protein synthesis. Muscle protein breakdown, assessed by 3-methylhistidine excretion, was inhibited by insulin but not by the IGF peptides.

No human half-life or other human pharmacokinetic figure exists in the records reviewed.

1996 review: naturally occurring N-terminal truncation, about 10-fold more potent in cells

Narrative review

Ballard FJ et al. Int J Biochem Cell Biol. 1996;28(10):1085-7. PMID 8930132.

Des(1-3)IGF-I is a truncated variant of human IGF-I with the tripeptide Gly-Pro-Glu absent from the N-terminus. It has been isolated from bovine colostrum, human brain and porcine uterus, and probably results from post-translational cleavage of IGF-I, so it is a naturally occurring fragment rather than an engineered construct. It is generally about 10-fold more potent than IGF-I at stimulating hypertrophy and proliferation of cultured cells, a consequence of much reduced binding to IGF-binding proteins caused by the absence of the glutamate at position 3. The review states that clinical opportunities for des(1-3)IGF-I had not yet been evaluated. PubChem returned no compound record on 9 October 2026 for des(1-3)IGF-I, DES(1-3)IGF1, IGF-1 DES or Insulin-Like Growth Factor I (4-70), human.

Participants / model
Chemical identity, not a clinical population
Treatment
Truncated IGF-I variant
Follow-up
Not applicable
Study design
Review of original reports
Funding
not stated in the source

IGF-1 LR3 is a different modification: it adds a 13-residue N-terminal extension and substitutes position 3. The two are separate molecules with separate records.

Read the original source
Rat pharmacokinetics: cleared about four times faster than IGF-I

Animal study

Ballard FJ et al. J Endocrinol. 1991;128(2):197-204. PMID 2005410.

After intravenous injection of labeled tracers into rats, most des(1-3)IGF-I radioactivity remained free rather than associating with binding proteins. Mean total plasma clearances were 4.59 ml/min per kg for des(1-3)IGF-I, 1.20 for IGF-I and 1.34 for IGF-II, so the truncated variant was cleared roughly four times faster than intact IGF-I. Mean steady-state volume of distribution was 461 ml/kg for des(1-3)IGF-I versus 167 and 181 for IGF-I and IGF-II. Radioactivity appeared in the kidneys more than in other organs for all three tracers.

Participants / model
Rats
Treatment
Intravenous labeled tracer
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

These are rat numbers from intravenous tracer doses. No human pharmacokinetic study exists for this molecule in the records reviewed.

Read the original source
Diabetic rats: 7-day infusion, nitrogen retention about 70% of insulin's effect

Animal study

Tomas FM et al. Biochem J. 1991;276 ( Pt 2)(Pt 2):547-54. PMID 1710892.

In streptozotocin-induced diabetic rats infused for 7 days, des(1-3)IGF-I at 1.08 mg/kg per day produced effects on body weight and nitrogen retention that were approximately 70% of those obtained with 25 or 30 units of insulin per kg per day, while IGF-I at 1.05 or 1.08 mg/kg per day produced about 30% and human growth hormone at 1.38 mg/kg per day was not effective. The improvements in nitrogen balance were accounted for in part by increases in muscle protein synthesis. Muscle protein breakdown, assessed by 3-methylhistidine excretion, was inhibited by insulin but not by the IGF peptides, and carcass fat increased substantially with insulin but not with the IGF peptides.

Participants / model
Streptozotocin-induced diabetic rats
Treatment
Continuous infusion of des(1-3)IGF-I, IGF-I, human growth hormone or insulin
Follow-up
7 days
Study design
Original preclinical study with active comparators
Funding
not stated in the source

This is systemic infusion in diabetic rats, not a site-specific injection in a trained person.

Read the original source

What risks are specific to this molecule?

The one risk signal is specific to this variant: 53% of transgenic mice overexpressing it in mammary tissue developed mammary adenocarcinomas by 23 months. No human dose, pharmacokinetics or safety data exist, and black market product was found to contain lower-quality, oxidized forms.

In transgenic mice overexpressing des(1-3)hIGF-I in mammary tissue, 53% developed mammary adenocarcinomas by 23 months of age, and hyperplastic mammary intraepithelial neoplasia lesions were present in nonlactating multiparous animals. Mammary tumor incidence was 2 to 3-fold greater than in nontransgenic females, and in bitransgenic mice carrying both the transgene and a mutant p53, tumor latency was reduced by 8 months compared with the other three genotypes.

This is lifetime transgenic overexpression in a tissue, not an injected dose, and it is the most direct published statement of the oncogenic potential of this specific variant. It is not a risk rate for a person using a vial.

The approved full-length IGF-1 drug is contraindicated in pediatric patients with malignant neoplasia or a history of malignancy, warns of severe hypoglycemia leading to hypoglycemic seizures because of insulin-like effects, and carries a warning for several observed cases of malignant neoplasia in treated pediatric patients. Those label facts describe a different molecule and are context only.

No human dose, pharmacokinetics or safety data exist for des(1-3)IGF-I. An antidoping laboratory analysing black market products found abundant signs of lower quality, oxidized peptide forms.

Transgenic mice: mammary adenocarcinomas in 53% by 23 months

Animal study

Hadsell DL et al. Oncogene. 2000;19(7):889-98. PMID 10702797.

In transgenic mice overexpressing des(1-3)hIGF-I in mammary tissue (WAP-DES), 53% developed mammary adenocarcinomas by 23 months of age, and hyperplastic mammary intraepithelial neoplasia lesions were present in nonlactating multiparous animals. Mammary tumor incidence in WAP-DES mice was 2 to 3-fold greater than in nontransgenic females, and in bitransgenic mice carrying both WAP-DES and a mutant p53, tumor latency was reduced by 8 months compared with the other three genotypes.

Participants / model
Transgenic and bitransgenic mice
Treatment
Tissue-specific transgenic overexpression, not injection
Follow-up
Followed to 23 months of age
Study design
Original preclinical study
Funding
not stated in the source

This is lifetime transgenic overexpression in a tissue, not an injected dose, and it is the most direct published statement of the oncogenic potential of this specific variant. It must not be read as a risk rate for a user.

Read the original source
INCRELEX label, version effective 5 August 2025: full-length IGF-1, pediatric indication, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INCRELEX (mecasermin) solution for subcutaneous injection, prescribing information, label version effective 5 August 2025. Set ID a8b27a1b-a611-4f91-ad22-76d4b390c3ae.

INCRELEX (mecasermin) is recombinant human IGF-1, 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 Da. It was approved under BLA 021839 on 30 August 2005 for growth failure in pediatric patients 2 years and older with severe primary IGF-1 deficiency or with growth hormone gene deletion who have developed neutralizing antibodies to growth hormone. It is contraindicated in patients with closed epiphyses and in pediatric patients with malignant neoplasia or a history of malignancy. Warnings include severe hypoglycemia leading to hypoglycemic seizures, because it has insulin-like hypoglycemic effects, anaphylaxis requiring hospitalization, and several observed cases of malignant neoplasia in treated pediatric patients, with instruction to discontinue if evidence of malignant neoplasia develops.

Participants / model
Pediatric patients 2 years and older with severe primary IGF-1 deficiency or growth hormone gene deletion with neutralizing antibodies to growth hormone
Treatment
INCRELEX solution for subcutaneous injection
Follow-up
Label version effective 5 August 2025
Study design
FDA prescribing information
Funding
not stated in the source

This is the full-length molecule, not the truncated variant, and the indication is pediatric growth failure, not muscle growth in adults. Nothing on it transfers to des(1-3)IGF-I except as context.

Read the original source
Searches, 9 October 2026: no tendon or ligament study, no human administration study

PubMed search record

PubMed search run on 9 October 2026: (des(1-3)IGF-I OR des(1-3)IGF-1) AND (tendon OR ligament OR muscle injury OR resistance exercise), 4 records. A second search for the same terms restricted to the humans MeSH term with clinical trial, healthy volunteers or administration, 9 records. A broader search on the compound names, 198 records.

The search for des(1-3)IGF-I or des(1-3)IGF-1 with tendon, ligament, muscle injury or resistance exercise returned 4 records, with titles covering expression of mechano growth factor in E. coli, IGF-I cardioprotection in myocardial ischemia and reperfusion, cell culture as a tool for identifying nutritional disease therapies, and IGFs as putative muscle-derived trophic agents for motoneuron survival; none names a tendon or ligament experiment. The same terms restricted to the humans MeSH term with clinical trial, healthy volunteers or administration returned 9 records, with titles covering two antidoping analytical methods, human neutrophil and neuroblastoma cell work, endometrial cancer cell receptor modulation, rat studies and a mammary gland development study; none is a human administration study. A broader search on the compound names returned 198 records, which are cell, rat and analytical work. The records reviewed contain no human dose, no human pharmacokinetics, no human safety data, no trial and no study of tendon or ligament repair by any route.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source
Antidoping analysis: black market product quality, rat intramuscular detection window

Animal study

Mongongu C et al. Drug Test Anal. 2021;13(7):1256-1269. PMID 33587816.

An antidoping laboratory validating a detection method states that IGF-I and its analogs LongR3-IGF-I, Des(1-3)-IGF-I and R3-IGF-I are prohibited substances in sport, were never approved for use in humans, and are readily available as black market products for bodybuilding. Analysing those black market products, the authors found abundant signs of lower quality, oxidized peptide forms, which is why their method monitors both the native and the mono-oxidized forms. After a single intramuscular administration at 100 micrograms/kg in rats, unchanged Des(1-3)-IGF-I and R3-IGF-I were detected until 24 hours after administration, while LongR3-IGF-I disappeared rapidly after 4 hours. The same degradation products appeared after in vitro incubation in human whole blood.

Participants / model
Black market product samples; rats for the administration study; human serum and whole blood for method work
Treatment
Intramuscular administration in rats; product analysis
Follow-up
Detection followed to 24 hours after administration
Study design
Original analytical study
Funding
not stated in the source

This is the one laboratory that analysed market product, and it reports quality problems. The rat result describes a detection window, not a benefit.

Read the original source

Why does des(1-3)IGF-1 sit in F tier?

No human benefit has been measured, and the published downside is specific to this variant. There is no trial, dose or safety data, no tendon or ligament study by any route, and 53% of transgenic mice overexpressing it developed mammary adenocarcinomas by 23 months.

The published human record is empty: no trial, no dose, no pharmacokinetics, no safety data, and nothing on tendon or ligament by any route. The published downside is specific and about this exact variant. Transgenic mice overexpressing des(1-3)hIGF-I developed mammary adenocarcinomas at a 53% rate by 23 months, and the approved full-length IGF-1 drug is contraindicated in pediatric patients with malignant neoplasia or a history of malignancy, carries a malignant neoplasia warning and warns of severe hypoglycemia with seizures.

The one laboratory that analysed market product found abundant lower-quality, oxidized forms, and the peptide is prohibited in sport. The molecule is a naturally occurring N-terminal truncation rather than an engineered extension, and it was cleared about four times faster than intact IGF-1 in rats rather than lasting longer.

Searches, 9 October 2026: no tendon or ligament study, no human administration study

PubMed search record

PubMed search run on 9 October 2026: (des(1-3)IGF-I OR des(1-3)IGF-1) AND (tendon OR ligament OR muscle injury OR resistance exercise), 4 records. A second search for the same terms restricted to the humans MeSH term with clinical trial, healthy volunteers or administration, 9 records. A broader search on the compound names, 198 records.

The search for des(1-3)IGF-I or des(1-3)IGF-1 with tendon, ligament, muscle injury or resistance exercise returned 4 records, with titles covering expression of mechano growth factor in E. coli, IGF-I cardioprotection in myocardial ischemia and reperfusion, cell culture as a tool for identifying nutritional disease therapies, and IGFs as putative muscle-derived trophic agents for motoneuron survival; none names a tendon or ligament experiment. The same terms restricted to the humans MeSH term with clinical trial, healthy volunteers or administration returned 9 records, with titles covering two antidoping analytical methods, human neutrophil and neuroblastoma cell work, endometrial cancer cell receptor modulation, rat studies and a mammary gland development study; none is a human administration study. A broader search on the compound names returned 198 records, which are cell, rat and analytical work. The records reviewed contain no human dose, no human pharmacokinetics, no human safety data, no trial and no study of tendon or ligament repair by any route.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 9 October 2026
Study design
Literature searches
Funding
not stated in the source

A search result shows what the databases returned on that date. It is not proof that no unindexed study exists.

Read the original source
Transgenic mice: mammary adenocarcinomas in 53% by 23 months

Animal study

Hadsell DL et al. Oncogene. 2000;19(7):889-98. PMID 10702797.

In transgenic mice overexpressing des(1-3)hIGF-I in mammary tissue (WAP-DES), 53% developed mammary adenocarcinomas by 23 months of age, and hyperplastic mammary intraepithelial neoplasia lesions were present in nonlactating multiparous animals. Mammary tumor incidence in WAP-DES mice was 2 to 3-fold greater than in nontransgenic females, and in bitransgenic mice carrying both WAP-DES and a mutant p53, tumor latency was reduced by 8 months compared with the other three genotypes.

Participants / model
Transgenic and bitransgenic mice
Treatment
Tissue-specific transgenic overexpression, not injection
Follow-up
Followed to 23 months of age
Study design
Original preclinical study
Funding
not stated in the source

This is lifetime transgenic overexpression in a tissue, not an injected dose, and it is the most direct published statement of the oncogenic potential of this specific variant. It must not be read as a risk rate for a user.

Read the original source
Antidoping analysis: black market product quality, rat intramuscular detection window

Animal study

Mongongu C et al. Drug Test Anal. 2021;13(7):1256-1269. PMID 33587816.

An antidoping laboratory validating a detection method states that IGF-I and its analogs LongR3-IGF-I, Des(1-3)-IGF-I and R3-IGF-I are prohibited substances in sport, were never approved for use in humans, and are readily available as black market products for bodybuilding. Analysing those black market products, the authors found abundant signs of lower quality, oxidized peptide forms, which is why their method monitors both the native and the mono-oxidized forms. After a single intramuscular administration at 100 micrograms/kg in rats, unchanged Des(1-3)-IGF-I and R3-IGF-I were detected until 24 hours after administration, while LongR3-IGF-I disappeared rapidly after 4 hours. The same degradation products appeared after in vitro incubation in human whole blood.

Participants / model
Black market product samples; rats for the administration study; human serum and whole blood for method work
Treatment
Intramuscular administration in rats; product analysis
Follow-up
Detection followed to 24 hours after administration
Study design
Original analytical study
Funding
not stated in the source

This is the one laboratory that analysed market product, and it reports quality problems. The rat result describes a detection window, not a benefit.

Read the original source
Rat pharmacokinetics: cleared about four times faster than IGF-I

Animal study

Ballard FJ et al. J Endocrinol. 1991;128(2):197-204. PMID 2005410.

After intravenous injection of labeled tracers into rats, most des(1-3)IGF-I radioactivity remained free rather than associating with binding proteins. Mean total plasma clearances were 4.59 ml/min per kg for des(1-3)IGF-I, 1.20 for IGF-I and 1.34 for IGF-II, so the truncated variant was cleared roughly four times faster than intact IGF-I. Mean steady-state volume of distribution was 461 ml/kg for des(1-3)IGF-I versus 167 and 181 for IGF-I and IGF-II. Radioactivity appeared in the kidneys more than in other organs for all three tracers.

Participants / model
Rats
Treatment
Intravenous labeled tracer
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

These are rat numbers from intravenous tracer doses. No human pharmacokinetic study exists for this molecule in the records reviewed.

Read the original source
INCRELEX label, version effective 5 August 2025: full-length IGF-1, pediatric indication, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INCRELEX (mecasermin) solution for subcutaneous injection, prescribing information, label version effective 5 August 2025. Set ID a8b27a1b-a611-4f91-ad22-76d4b390c3ae.

INCRELEX (mecasermin) is recombinant human IGF-1, 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 Da. It was approved under BLA 021839 on 30 August 2005 for growth failure in pediatric patients 2 years and older with severe primary IGF-1 deficiency or with growth hormone gene deletion who have developed neutralizing antibodies to growth hormone. It is contraindicated in patients with closed epiphyses and in pediatric patients with malignant neoplasia or a history of malignancy. Warnings include severe hypoglycemia leading to hypoglycemic seizures, because it has insulin-like hypoglycemic effects, anaphylaxis requiring hospitalization, and several observed cases of malignant neoplasia in treated pediatric patients, with instruction to discontinue if evidence of malignant neoplasia develops.

Participants / model
Pediatric patients 2 years and older with severe primary IGF-1 deficiency or growth hormone gene deletion with neutralizing antibodies to growth hormone
Treatment
INCRELEX solution for subcutaneous injection
Follow-up
Label version effective 5 August 2025
Study design
FDA prescribing information
Funding
not stated in the source

This is the full-length molecule, not the truncated variant, and the indication is pediatric growth failure, not muscle growth in adults. Nothing on it transfers to des(1-3)IGF-I except as context.

Read the original source

Studies and sources

1996 review: naturally occurring N-terminal truncation, about 10-fold more potent in cells

Narrative review

Ballard FJ et al. Int J Biochem Cell Biol. 1996;28(10):1085-7. PMID 8930132.

Des(1-3)IGF-I is a truncated variant of human IGF-I with the tripeptide Gly-Pro-Glu absent from the N-terminus. It has been isolated from bovine colostrum, human brain and porcine uterus, and probably results from post-translational cleavage of IGF-I, so it is a naturally occurring fragment rather than an engineered construct. It is generally about 10-fold more potent than IGF-I at stimulating hypertrophy and proliferation of cultured cells, a consequence of much reduced binding to IGF-binding proteins caused by the absence of the glutamate at position 3. The review states that clinical opportunities for des(1-3)IGF-I had not yet been evaluated. PubChem returned no compound record on 9 October 2026 for des(1-3)IGF-I, DES(1-3)IGF1, IGF-1 DES or Insulin-Like Growth Factor I (4-70), human.

Participants / model
Chemical identity, not a clinical population
Treatment
Truncated IGF-I variant
Follow-up
Not applicable
Study design
Review of original reports
Funding
not stated in the source

IGF-1 LR3 is a different modification: it adds a 13-residue N-terminal extension and substitutes position 3. The two are separate molecules with separate records.

Read the original source
INCRELEX label, version effective 5 August 2025: full-length IGF-1, pediatric indication, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. INCRELEX (mecasermin) solution for subcutaneous injection, prescribing information, label version effective 5 August 2025. Set ID a8b27a1b-a611-4f91-ad22-76d4b390c3ae.

INCRELEX (mecasermin) is recombinant human IGF-1, 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 Da. It was approved under BLA 021839 on 30 August 2005 for growth failure in pediatric patients 2 years and older with severe primary IGF-1 deficiency or with growth hormone gene deletion who have developed neutralizing antibodies to growth hormone. It is contraindicated in patients with closed epiphyses and in pediatric patients with malignant neoplasia or a history of malignancy. Warnings include severe hypoglycemia leading to hypoglycemic seizures, because it has insulin-like hypoglycemic effects, anaphylaxis requiring hospitalization, and several observed cases of malignant neoplasia in treated pediatric patients, with instruction to discontinue if evidence of malignant neoplasia develops.

Participants / model
Pediatric patients 2 years and older with severe primary IGF-1 deficiency or growth hormone gene deletion with neutralizing antibodies to growth hormone
Treatment
INCRELEX solution for subcutaneous injection
Follow-up
Label version effective 5 August 2025
Study design
FDA prescribing information
Funding
not stated in the source

This is the full-length molecule, not the truncated variant, and the indication is pediatric growth failure, not muscle growth in adults. Nothing on it transfers to des(1-3)IGF-I except as context.

Read the original source
Rat pharmacokinetics: cleared about four times faster than IGF-I

Animal study

Ballard FJ et al. J Endocrinol. 1991;128(2):197-204. PMID 2005410.

After intravenous injection of labeled tracers into rats, most des(1-3)IGF-I radioactivity remained free rather than associating with binding proteins. Mean total plasma clearances were 4.59 ml/min per kg for des(1-3)IGF-I, 1.20 for IGF-I and 1.34 for IGF-II, so the truncated variant was cleared roughly four times faster than intact IGF-I. Mean steady-state volume of distribution was 461 ml/kg for des(1-3)IGF-I versus 167 and 181 for IGF-I and IGF-II. Radioactivity appeared in the kidneys more than in other organs for all three tracers.

Participants / model
Rats
Treatment
Intravenous labeled tracer
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

These are rat numbers from intravenous tracer doses. No human pharmacokinetic study exists for this molecule in the records reviewed.

Read the original source
Diabetic rats: 7-day infusion, nitrogen retention about 70% of insulin's effect

Animal study

Tomas FM et al. Biochem J. 1991;276 ( Pt 2)(Pt 2):547-54. PMID 1710892.

In streptozotocin-induced diabetic rats infused for 7 days, des(1-3)IGF-I at 1.08 mg/kg per day produced effects on body weight and nitrogen retention that were approximately 70% of those obtained with 25 or 30 units of insulin per kg per day, while IGF-I at 1.05 or 1.08 mg/kg per day produced about 30% and human growth hormone at 1.38 mg/kg per day was not effective. The improvements in nitrogen balance were accounted for in part by increases in muscle protein synthesis. Muscle protein breakdown, assessed by 3-methylhistidine excretion, was inhibited by insulin but not by the IGF peptides, and carcass fat increased substantially with insulin but not with the IGF peptides.

Participants / model
Streptozotocin-induced diabetic rats
Treatment
Continuous infusion of des(1-3)IGF-I, IGF-I, human growth hormone or insulin
Follow-up
7 days
Study design
Original preclinical study with active comparators
Funding
not stated in the source

This is systemic infusion in diabetic rats, not a site-specific injection in a trained person.

Read the original source
Antidoping analysis: black market product quality, rat intramuscular detection window

Animal study

Mongongu C et al. Drug Test Anal. 2021;13(7):1256-1269. PMID 33587816.

An antidoping laboratory validating a detection method states that IGF-I and its analogs LongR3-IGF-I, Des(1-3)-IGF-I and R3-IGF-I are prohibited substances in sport, were never approved for use in humans, and are readily available as black market products for bodybuilding. Analysing those black market products, the authors found abundant signs of lower quality, oxidized peptide forms, which is why their method monitors both the native and the mono-oxidized forms. After a single intramuscular administration at 100 micrograms/kg in rats, unchanged Des(1-3)-IGF-I and R3-IGF-I were detected until 24 hours after administration, while LongR3-IGF-I disappeared rapidly after 4 hours. The same degradation products appeared after in vitro incubation in human whole blood.

Participants / model
Black market product samples; rats for the administration study; human serum and whole blood for method work
Treatment
Intramuscular administration in rats; product analysis
Follow-up
Detection followed to 24 hours after administration
Study design
Original analytical study
Funding
not stated in the source

This is the one laboratory that analysed market product, and it reports quality problems. The rat result describes a detection window, not a benefit.

Read the original source
Transgenic mice: mammary adenocarcinomas in 53% by 23 months

Animal study

Hadsell DL et al. Oncogene. 2000;19(7):889-98. PMID 10702797.

In transgenic mice overexpressing des(1-3)hIGF-I in mammary tissue (WAP-DES), 53% developed mammary adenocarcinomas by 23 months of age, and hyperplastic mammary intraepithelial neoplasia lesions were present in nonlactating multiparous animals. Mammary tumor incidence in WAP-DES mice was 2 to 3-fold greater than in nontransgenic females, and in bitransgenic mice carrying both WAP-DES and a mutant p53, tumor latency was reduced by 8 months compared with the other three genotypes.

Participants / model
Transgenic and bitransgenic mice
Treatment
Tissue-specific transgenic overexpression, not injection
Follow-up
Followed to 23 months of age
Study design
Original preclinical study
Funding
not stated in the source

This is lifetime transgenic overexpression in a tissue, not an injected dose, and it is the most direct published statement of the oncogenic potential of this specific variant. It must not be read as a risk rate for a user.

Read the original source

Why is IGF-1 DES in F tier?

F fits a molecule with no measured human benefit and a specific published harm signal. There are no human dose, pharmacokinetic or safety data and no tendon or ligament study by any route, the closest muscle result is a 7-day infusion in diabetic rats, and transgenic overexpression produced mammary adenocarcinomas in 53% of mice by 23 months. The one laboratory that analysed market product found abundant lower-quality, oxidized forms.