Key papers ✓ 2✗ 3~ 4? 2

• ✓ Positive animalBiochem J · 1992

  Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats.

  Animalssize not reported7 days

  Animal study, IGF-I and analogues (des(1-3)IGF-I, LR3IGF-I) via subcutaneous osmotic pumps

  In rats made catabolic with dexamethasone, LR3IGF-I was about 2.5-fold more potent than IGF-I at improving weight and nitrogen retention, though carcass (muscle) weights stayed low and gut weight rose up to 45%.

  Key resultHighest IGF-I dose (695 µg/day) gave a 6 g body weight increase over 7 days vs a 19 g loss in the dexamethasone-only group; the analogues were approx. 2.5-fold more potent than IGF-I.

  Study details

  Studied

  150 g male rats made catabolic with dexamethasone (20 µg/day)

  Compared with

  Dexamethasone-only and pair-fed controls; native IGF-I

  Main outcome

  Body weight, nitrogen retention, muscle protein synthesis and breakdown

  Authors' conclusion

  IGF-I partially reversed dexamethasone-induced catabolism, and analogues that bind weakly to IGF-binding proteins were more potent, showing potential of IGF-I variants in catabolic states.

  Limitations

  Rat study; group sizes not stated in abstract.

  DOI 10.1042/bj2820091PubMed 1371669Free full text
• ~ Mixed animalJ Endocrinol · 1996

  Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection.

  Animalssize not reportedSham/vehicle control7 days

  Animal study comparing LR3IGF-I and IGF-I by continuous infusion vs once- or twice-daily injection

  In rats, LR3IGF-I was 1.5-2x more potent than IGF-I for weight gain and organ growth, but barely equal to IGF-I at reversing dexamethasone-induced muscle loss.

  Key resultBy injection, methylhistidine excretion in dexamethasone-treated rats was reduced to a threefold greater extent by LR3IGF-I than by IGF-I; infused LR3IGF-I was generally 1.5- to 2-fold more potent than IGF-I.

  Study details

  Studied

  Normal growing rats (150 g) and dexamethasone-treated catabolic rats

  Compared with

  IGF-I; vehicle

  Main outcome

  Body weight gain, organ weights, feed efficiency, methylhistidine excretion

  Authors' conclusion

  LR3IGF-I kept superior potency to IGF-I for several actions when injected, though much reduced vs infusion; low-binding-protein analogues may have advantages where injection is necessary.

  Limitations

  Rat study; LR3IGF-I was only barely equipotent with IGF-I for restoring carcass muscle.

  DOI 10.1677/joe.0.1500077PubMed 8708565
• ✗ Negative animalJ Endocrinol · 1997

  Long [R3] insulin-like growth factor-I reduces growth, plasma growth hormone, IGF binding protein-3 and endogenous IGF-I concentrations in pigs.

  Animalssize not reported4-day infusion

  Animal infusion study of IGF-I or LR3IGF-I, alone or with porcine GH

  In finisher pigs, a 4-day LR3IGF-I infusion decreased daily weight gain and food intake and suppressed GH, IGF-I, IGFBP-3 and insulin.

  Key resultLR3IGF-I (180 µg/kg/day) decreased average daily gain, food intake and plasma IGFBP-3, IGF-I and insulin; mean plasma GH fell 23% and area under GH peaks 60%.

  Study details

  Studied

  Finisher pigs

  Compared with

  IGF-I; porcine GH combination

  Main outcome

  Growth performance and plasma hormones

  Authors' conclusion

  Both IGF-I and LR3IGF-I suppress plasma GH in finisher pigs, which may contribute to LR3IGF-I's inhibitory effect on growth in the pig (unlike the rat).

  Limitations

  Pig study; group sizes not stated in abstract.

  DOI 10.1677/joe.0.1550559PubMed 9488001
• ✗ Negative animalJ Endocrinol · 1995

  Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces plasma IGF-I, IGF-II and IGF binding protein concentrations in the guinea pig.

  Animalssize not reportedSham/vehicle control7 days

  Animal study of continuous infusion of IGF-I, IGF-II or LR3IGF-I

  In guinea pigs, 7 days of LR3IGF-I enlarged adrenals, gut, kidneys and spleen but did not increase overall body growth or change carcass composition.

  Key resultBody weight gain, feed intake and carcass composition were not significantly affected by any treatment; LR3IGF-I significantly increased fractional weights of adrenals, gut, kidneys and spleen.

  Study details

  Studied

  Female guinea pigs (350 g)

  Compared with

  Vehicle infusion

  Main outcome

  Body weight gain, feed conversion, carcass composition, organ weights

  Authors' conclusion

  Chronic IGF infusion did not stimulate overall growth in guinea pigs, possibly because total circulating IGF concentrations were not increased.

  Limitations

  Guinea pig study; abstract truncated.

  DOI 10.1677/joe.0.1460247PubMed 7561636
• ? Inconclusive animalJ Endocrinol · 1997

  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.

  Animalssize not reportedBlood sampled from 30 min before to 4 h after injection

  Animal bolus injection dose-response comparison of IGF-I and variants including LR3IGF-I

  In pigs, LR3IGF-I and related variants lowered blood glucose 2-3x more potently and for longer than native IGF-I (about 4-8x greater cumulative hypoglycemia), a potential safety concern.

  Key resultIGF variants were consistently 2- to 3-fold more potent than IGF-I for lowering plasma glucose; cumulative suppression over four hours was approximately 4- to 8-fold greater.

  Study details

  Studied

  Marmoset monkeys (anaesthetised and conscious) and pigs

  Compared with

  Native IGF-I; insulin in pigs

  Main outcome

  Plasma glucose lowering and duration

  Authors' conclusion

  Variants binding poorly to IGFBPs have more potent, prolonged hypoglycaemic action than IGF-I in these animals, suggesting possible superior efficacy, especially des(1-3)IGF-I, as an adjunct to insulin.

  Limitations

  Acute animal study; group sizes not stated in abstract.

  DOI 10.1677/joe.0.1550377PubMed 9415072
• ✓ Positive animalGrowth Factors · 1994

  Treatment with IGF-I peptides improves function of the remnant gut following small bowel resection in rats.

  Animalssize not reported7 days

  Animal study of subcutaneous IGF-I, LR3IGF-I and des(1-3)IGF-I

  In rats after removal of most of the small bowel, LR3IGF-I reduced fat and nitrogen malabsorption and increased weight gain and gut growth.

  Key resultAt 278 µg/day, IGF-I, LR3IGF-I or des(1-3)IGF-I significantly attenuated fat and nitrogen malabsorption after 70% resection; total gut weight increased by up to 21%.

  Study details

  Studied

  Growing rats after 70% or 80% jejuno-ileal resection

  Compared with

  IGF-I vs analogues

  Main outcome

  Gut growth, fat and nitrogen absorption, body weight gain

  Authors' conclusion

  IGF-I peptides improved gastrointestinal absorptive function after partial gut resection, likely via increased absorptive surface area.

  Limitations

  Rat study; responses weaker after 80% resection.

  DOI 10.3109/08977199409010990PubMed 7803042
• ? Inconclusive reviewFront Endocrinol (Lausanne) · 2026

  The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration.

  No new data

  Narrative review of unregulated GH-IGF-1 axis peptides including PEG-MGF

  Narrative review placing IGF-1 LR3 among unregulated GH/IGF-axis peptides with little or no human study, flagging dysglycaemia and theoretical mitogenic risks.

  Study details

  Authors' conclusion

  Peptides are stratified into evidence tiers from regulatory-grade trial data to no human studies; performance benefits are uncertain, and the authors propose a clinical assessment algorithm without legitimising off-label use.

  Limitations

  Narrative review; some peptides lack human studies.

  DOI 10.3389/fendo.2026.1822475PubMed 42395176Free full text
  Figure 2 Figure 1
• ✗ Negative animalAm J Physiol Endocrinol Metab · 2025

  IGF-1 LR3 does not promote growth in late-gestation growth-restricted fetal sheep.

  Animalssize not reportedSham/vehicle control1 week

  Vehicle-controlled 1-week infusion

  A 1-week IGF-1 LR3 infusion into growth-restricted fetal sheep (7 treated, 7 vehicle) did not improve fetal weight and lowered circulating amino acids.

  Key resultFetal body weight, insulin, glucose, oxygen and GSIS did not differ between groups; amino acids fell in the LR3 group (P = 0.0232)

  Study details

  Studied

  Late-gestation growth-restricted fetal sheep

  Compared with

  Vehicle

  Main outcome

  Fetal body weight, insulin, glucose, oxygen, glucose-stimulated insulin secretion, amino acids

  Sample

  7 treated and 7 vehicle fetal sheep (14 total, summed from the abstract)

  Authors' conclusion

  One week of IGF-1 LR3 did not improve growth in growth-restricted fetuses; falling amino acids may mean amino acid supply limits any growth effect.

  Limitations

  Fetal sheep; small groups; lower dose than the authors' earlier normal-fetus study.

  DOI 10.1152/ajpendo.00259.2024PubMed 39679943Free full text
• ~ Mixed animalJ Dev Orig Health Dis · 2023

  Attenuated glucose-stimulated insulin secretion during an acute IGF-1 LR3 infusion into fetal sheep does not persist in isolated islets.

  Animals10 animalsSham/vehicle control90-minute infusion

  Acute in vivo infusion with hyperglycemic clamp, then in vitro islet testing

  A 90-minute IGF-1 LR3 infusion lowered plasma insulin and glucose-stimulated insulin secretion in fetal sheep, but islets isolated afterwards recovered their insulin secretion in vitro.

  Study details

  Studied

  Late-gestation fetal sheep and their isolated pancreatic islets

  Compared with

  Vehicle control

  Main outcome

  Insulin concentrations, in vivo and in vitro glucose-stimulated insulin secretion

  Sample

  10 fetal sheep infused in vivo; 6 per group for islet studies

  Authors' conclusion

  IGF-1 LR3 acutely lowered fetal insulin secretion in vivo, but isolated islets retained the ability to recover secretion, which may matter for long-term effects of growth-restriction therapies.

  Limitations

  Animal study with small groups; no human data.

  DOI 10.1017/S2040174423000090PubMed 37114757Free full text
• ~ Mixed animalJ Alzheimers Dis · 2025

  Intranasal long R3 insulin-like growth factor-1 treatment promotes amyloid plaque remodeling in cerebral cortex but fails to preserve cognitive function in male 5XFAD mice.

  Animals19-27 mice per groupSham/vehicle control7 months

  Vehicle-controlled intranasal treatment with behavioural, imaging and tissue analysis, plus BV-2 microglial cell experiments

  In male 5XFAD Alzheimer's-model mice, 7 months of intranasal LR3-IGF-1 improved body composition and remodelled amyloid plaques but did not preserve cognition.

  Study details

  Studied

  Male wildtype and 5XFAD mice, treated from 3 to 10 months of age

  Compared with

  Intranasal vehicle

  Main outcome

  Cognition and behaviour; amyloid-beta pathology; body composition

  Authors' conclusion

  LR3 had favourable effects on amyloid plaque remodelling in cortex but failed to preserve behaviour or memory, so the data do not support it as a monotherapy.

  Limitations

  Male mice of one transgenic model only.

  DOI 10.1177/13872877241299056PubMed 39610283Free full text
• ~ Mixed animalBr J Nutr · 2002

  Insulin-like growth factor-I and analogues increase growth in artificially-reared neonatal pigs.

  Animalssize not reported8 days (experiment 1); 18 days (experiment 2)

  Infusion experiments of control, IGF-I or LR3IGF-I at several rates

  In artificially reared neonatal pigs, IGF-I and LR3IGF-I infusion did not change weight gain in limit-fed piglets, but ad libitum-fed pigs infused with LR3IGF-I gained more weight than controls (457 vs 386 g/d, P<0.01) and IGF-I did not.

  Key resultWeight gain over the second 9 days: 457 g/d with LR3IGF-I vs 386 g/d control (P<0.01); IGF-I 413 g/d (P=0.15)

  Study details

  Studied

  Artificially reared neonatal pigs

  Compared with

  Control saline; IGF-I

  Main outcome

  Daily weight gain, milk intake, plasma IGF concentrations

  Sample

  Two experiments in neonatal pigs (42 in the first, 18 in the second, spelled out in the abstract)

  Authors' conclusion

  IGF-I, and particularly LR3IGF-I, can increase growth rate and milk intake in ad libitum-fed artificially reared pigs but not in limit-fed piglets.

  Limitations

  Neonatal pig study; effect depended on feeding regimen.

  DOI 10.1079/BJNBJN2002574PubMed 12067429

Reported side effects

No human safety data in the published literature; animal studies show potent, prolonged hypoglycemia and suppression of the body's own GH/IGF-I.

9 registered human trials (0 active)

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