Skip to content
StackItSmart
DPreclinical / mechanistic only
High riskHypoglycemia riskNo human data

IGF-1 LR3

Long R3 IGF-1

IGF-1 LR3 (Long R3 IGF-1) is a synthetic, potency-enhanced analog of human insulin-like growth factor-1 that was originally manufactured as a cell-culture research reagent, not a medicine. It carries an arginine-for-glutamate substitution at position 3 plus a 13-amino-acid N-terminal extension, which sharply reduce its binding to IGF-binding proteins so that more of the peptide circulates in a free, biologically active form and for longer than native IGF-1. It is used non-medically in an attempt to drive muscle and tissue growth. There are no human studies of this specific compound: its dosing, pharmacokinetics, and safety in people are essentially unknown, and injectable products sold under this name are frequently mislabeled or are contaminated research by-products (e.g., His-tagged versions never intended for human use). Foreseeable harms, extrapolated from the closely related approved drug mecasermin (recombinant human IGF-1) and from IGF-1 biology, include potentially severe hypoglycemia, fluid retention, tissue and organ overgrowth, and a biologically plausible but unquantified concern about promoting cancer, because higher IGF-1 signaling drives cell proliferation and correlates with cancer risk in humans. This is a high-uncertainty, high-risk substance; anyone using or considering it should involve a physician and obtain bloodwork rather than self-experiment.

Clinical readoutPeptide · igf
Hepatic strainNone
CardiovascularModerate
HPTA suppressionNone
Half-life
15 min
Route
Non-medical use is by s…
Evidence
D
Active
Unknown in humans
15 min30 min45 min1 h1.3 h
Illustrative single-compartment washout · each mark = one half-life · t½ ≈ Not established in humans for the LR3 analog. Native free IGF-1 has a very short circulating half-life (roughly 10-20 minutes) when unbound, whereas IGFBP-bound IGF-1 persists for ~12-16 hours; the LR3 design deliberately evades IGFBP sequestration, which is expected to extend its bioactive presence relative to free native IGF-1, but no validated human half-life exists. Longer figures circulated in non-clinical sources are unverified.
Pharmacology

Mechanism of action

IGF-1 LR3 binds and activates the type 1 IGF receptor (IGF-1R), a receptor tyrosine kinase, triggering the PI3K/AKT and Ras/MAPK (ERK1/2) intracellular cascades that drive cell growth, proliferation, protein synthesis, and inhibition of apoptosis; it also cross-reacts partially with the insulin receptor, producing insulin-like glucose-lowering effects. The defining pharmacologic feature of the LR3 modification is that the Arg3 substitution plus the N-terminal extension markedly lower affinity for IGF-binding proteins (IGFBPs), so unlike native IGF-1 the analog is not sequestered in the circulating IGFBP-3/acid-labile-subunit ternary complex; this leaves a much larger free, receptor-available fraction and is the basis for its greater and more prolonged bioactivity in laboratory systems. All of this mechanism is established in cell-culture and animal models; no human mechanistic or dose-response data exist for the LR3 analog itself.
Kinetics

Pharmacokinetics

Half-life

Not established in humans for the LR3 analog. Native free IGF-1 has a very short circulating half-life (roughly 10-20 minutes) when unbound, whereas IGFBP-bound IGF-1 persists for ~12-16 hours; the LR3 design deliberately evades IGFBP sequestration, which is expected to extend its bioactive presence relative to free native IGF-1, but no validated human half-life exists. Longer figures circulated in non-clinical sources are unverified.

Active duration

Unknown in humans; presumed longer-acting than native free IGF-1 because it resists IGFBP binding and clearance, but there are no human PK studies to confirm duration. This monograph reports PK only to inform monitoring/washout windows, not to guide timing of use.

Route

Non-medical use is by subcutaneous or intramuscular injection; its legitimate use is as an in-vitro cell-culture additive. Long-R3-IGF-I is detectable in urine by anti-doping mass spectrometry and is prohibited in sport.

Metabolism & clearance

As a ~9 kDa peptide it is expected to be cleared by proteolytic degradation in tissues and by renal filtration/catabolism, similar to native IGF-1; specific human metabolism and clearance data for the LR3 analog are not available.

For monitoring and washout planning, not drug-test evasion.

Reported effects

Physiological & performance effects

  • Activates IGF-1R signaling, which in preclinical models promotes cellular proliferation, protein synthesis, and anabolic/growth effects in muscle and other tissues
  • Insulin-like activity that lowers blood glucose
  • In an animal (mouse) model, intranasal LR3-IGF-1 improved body composition but did not preserve cognition, illustrating potent metabolic activity without proven clinical benefit
  • Suppresses endogenous pituitary growth hormone secretion through IGF-1 negative feedback (a class/mechanistic effect of raising IGF-1 signaling)
  • Claimed physique and performance benefits in humans are unproven - there are no human efficacy studies of IGF-1 LR3
Safety

Adverse effects by system

Cardiovascular

No human data for IGF-1 LR3. Concern is extrapolated: chronic IGF-1 excess (as in acromegaly) and animal studies of recombinant IGF-1 are associated with cardiac hypertrophy and organ enlargement, and fluid retention/edema is reported across the performance-peptide class. Potential for cardiac hypertrophy and fluid retention should be assumed but is unquantified.

Hepatic

No evidence of direct hepatotoxicity and no human data for the LR3 analog. As an injected peptide it is not subject to the first-pass hepatic metabolism that makes oral 17-alpha-alkylated steroids liver-toxic; the liver is the main site of IGF-1 production rather than a target of peptide-induced injury. Hepatic safety is nonetheless unstudied for this compound.

Endocrine / HPTA

Raising IGF-1 signaling suppresses endogenous pituitary growth hormone via negative feedback; insulin-like action can cause hypoglycemia. Prolactin, cortisol, and appetite/dysglycemia changes are reported across the broader GH/IGF-1 performance-peptide class. There is no evidence that IGF-1 LR3 directly suppresses the hypothalamic-pituitary-gonadal (testosterone) axis, and no human endocrine data exist for it specifically.

Reproductive

No human reproductive or fertility data for IGF-1 LR3. IGF-1 has physiologic roles in gonadal function, but effects of the analog on reproduction are unknown. It should be assumed unsafe in pregnancy given its potent growth-promoting activity and absence of safety data.

Neuropsychiatric

No established psychiatric adverse-effect profile and no human data for the LR3 analog. In a small mecasermin (rhIGF-1) trial, mood and anxiety measures improved rather than worsened. Hypoglycemia from insulin-like activity can cause neuroglycopenic symptoms (confusion, anxiety, irritability, in severe cases seizure or loss of consciousness).

Renal

No human data for IGF-1 LR3. IGF-1 increases renal size and glomerular filtration, and animal studies of recombinant IGF-1 showed kidney (as well as spleen and heart) hypertrophy; nephromegaly/altered renal function is a plausible but unquantified concern.

Hematologic

No established hematologic effect and no human data for IGF-1 LR3. IGF-1 has mild mitogenic/erythropoietic roles physiologically, but clinically relevant hematologic effects of the analog are undocumented.

Dermatologic

Injection-site reactions are reported across the self-administered performance-peptide class. Chronic supraphysiologic IGF-1 could theoretically produce acromegaly-like soft-tissue and skin changes. No human dermatologic data exist for IGF-1 LR3 specifically.

Recovery

HPTA suppression & recovery

Suppression: Not a classic hypothalamic-pituitary-gonadal (testosterone) suppressor; primary endocrine effect is negative feedback suppression of pituitary growth hormone. HPG-axis impact in humans is unstudied and unknown.

Because IGF-1 LR3 is not a sex-steroid and has no human data, standard testosterone-recovery/SERM frameworks do not clearly apply, and this monograph does not endorse any post-use hormonal protocol. Any suspected endocrine disturbance (persistent GH/IGF-1 axis abnormalities, hypoglycemia, or gonadal symptoms) should be evaluated and managed by an endocrinologist with appropriate bloodwork; do not self-treat. If a SERM is ever considered for a genuine hormonal issue, that is a single-agent decision for a physician, not a self-directed stack.

Bloodwork & vitals

Monitoring

Recommended labs & checks
Fasting blood glucose and HbA1c (hypoglycemia is the best-characterized IGF-1 risk)Serum IGF-1 levelComplete blood count (CBC)Comprehensive metabolic panel including renal and hepatic functionAge-appropriate cancer screening per clinician (e.g., PSA discussion in men, given IGF-1/prostate-cancer association)Dilated funduscopic/ophthalmologic exam if any visual symptoms or diabetic retinopathy risk

Cadence: Establish a physician-supervised baseline before any exposure; if used, recheck glucose frequently early on (hypoglycemia can be acute), and reassess metabolic labs, IGF-1, CBC, and renal/hepatic panels periodically (e.g., every 4-8 weeks) with cancer and eye surveillance on a clinician-defined schedule. Because there are no validated human protocols, monitoring intervals should be set by the treating clinician.

Warning signs — seek care
  • Hypoglycemia symptoms: shakiness, sweating, palpitations, confusion, blurred vision, seizure or loss of consciousness (a medical emergency)
  • Severe or persistent headache, nausea, or visual disturbance (possible intracranial hypertension)
  • New or enlarging lumps/masses, or unexplained weight loss (possible malignancy)
  • Progressive swelling/edema, shortness of breath, or exertional intolerance (fluid retention/cardiac strain)
  • Enlargement of hands, feet, jaw, or facial features (acromegaly-like tissue overgrowth)
  • Jaw/facial changes, joint pain, or numbness/tingling (e.g., carpal tunnel from soft-tissue growth)
  • Injection-site pain, redness, swelling, or signs of infection
Do not use if

Contraindications

  • Active or prior malignancy, or elevated personal/family cancer risk (IGF-1 signaling is pro-proliferative and circulating IGF-1 is associated with higher prostate cancer risk)
  • Diabetes or use of insulin/sulfonylureas/other glucose-lowering agents (additive hypoglycemia risk)
  • Proliferative or active diabetic retinopathy (risk of progression with IGF-1 signaling)
  • Pregnancy and breastfeeding (potent growth factor, no safety data)
  • Children/adolescents with open growth plates outside of specialist medical supervision
  • History of benign intracranial hypertension (reported with recombinant IGF-1/mecasermin)
  • Any use without physician oversight and laboratory monitoring, given the complete absence of human safety data and high rate of product mislabeling/contamination
Combinations

Interaction profile

  • ModerateWith an anabolic steroid: Additive cardiovascular strain
  • MajorWith insulin: Metabolic / glucose
  • ModerateWith growth hormone: Metabolic / glucose
  • ContraindicatedWith DNP: Additive cardiovascular strain

Check a specific combination in the interaction checker.

Harm reduction

Reducing harm & when to stop

  • Recognize the core problem: there are no human safety or dosing studies of IGF-1 LR3, so any use is uncontrolled self-experimentation with an unknown risk profile.
  • Products sold as IGF-1 LR3 are frequently mislabeled, underdosed, or are research by-products (e.g., His-tagged variants never meant for injection); purity, identity, and sterility cannot be assumed.
  • Hypoglycemia is the most immediate documented danger of IGF-1 activity - keep fast-acting carbohydrate available, never combine with insulin or other glucose-lowering drugs, and treat confusion/sweating/shakiness urgently; severe hypoglycemia (seizure, unconsciousness) is a medical emergency requiring 911/emergency care.
  • Do not use with a personal or strong family history of cancer, and understand that promoting IGF-1 signaling is biologically linked to cancer risk.
  • Involve a physician, establish baseline bloodwork (glucose/HbA1c, IGF-1, CBC, renal and hepatic panels), and arrange ongoing monitoring rather than self-directing.
  • Stop and seek medical care for: severe or persistent headache or visual changes, new or growing lumps, progressive swelling or breathlessness, acromegaly-like growth of hands/feet/jaw, or any hypoglycemic emergency.
  • This monograph is informational and risk-focused; it does not endorse use, provide dosing to maximize effect, or address sourcing.
Evidence

Citations (11)

Every clinical claim above is tied to a primary source. Overall evidence grade D — this compound lacks adequate human data; claims rest on preclinical or mechanistic evidence.

  1. 01

    IGF-1 LR3 is an unregulated IGF-1 analog used for physique/performance with a complete absence of human studies, and reported class adverse effects include dysglycemia, fluid retention, myalgia/arthralgia, injection-site reactions, and prolactin/cortisol changes, plus biologically plausible but unproven mitogenic (cancer) concerns

    ReviewThe emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration.PMID 42395176 ↗

  2. 02

    LR3-IGF-1 is a potent IGF-1 analog; in a mouse model intranasal LR3-IGF-1 improved body composition but did not preserve cognition (illustrating potent activity without proven clinical benefit)

    PreclinicalPMID 39610283 ↗

  3. 03

    LONG R3 IGF-1 activates ERK1/2 (MAPK) signaling and exerts growth-promoting tissue effects in animal models; representative preclinical dosing was 150 micrograms/kg intraperitoneally twice daily in mice

    PreclinicalPMID 37301443 ↗

  4. 04

    IGF-1/IGF-1R signaling proceeds through PI3K/AKT and Ras/MAPK(ERK1/2) pathways to drive cell proliferation and survival

    ReviewPMID 34452353 ↗

  5. 05

    Long-R3-IGF-I is produced for biochemical/cell-culture research; a black-market injection vial was found to contain a His-tagged Long-R3-IGF-I whose effects in humans have never been elucidated, highlighting product mislabeling/contamination risk

    Case reportPMID 20675162 ↗

  6. 06

    Long-R-IGF-I is a prohibited doping agent detectable in urine by mass spectrometry

    PreclinicalPMID 38197510 ↗

  7. 07

    Recombinant human IGF-1 (mecasermin), the closest approved analog, was tolerated in a small phase 1 trial without hypoglycemia or serious adverse events at the doses used and showed nonlinear pharmacokinetics; unbound IGF-1 has a short serum half-life

    CohortPMID 24623853 ↗

  8. 08

    Main short-term adverse effects of recombinant IGF-1 (mecasermin) are hypoglycemia, headache, and intracranial hypertension, with lymphoid/tonsillar hypertrophy; animal studies showed kidney, spleen, and heart hypertrophy and carcinogenic effects, with human cancer risk unknown

    ReviewPMID 19637420 ↗

  9. 09

    Administration of unbound recombinant human IGF-1 is associated with hypoglycemia, and its serum half-life is influenced by IGFBP-3/acid-labile-subunit binding

    ReviewPMID 16610982 ↗

  10. 10

    With mecasermin therapy adverse events (including hypoglycemia) are common though rarely severe enough to modify treatment

    ReviewPMID 19627167 ↗

  11. 11

    Higher circulating IGF-I concentration is associated with increased prostate cancer risk (highest vs lowest fifth OR 1.29, 95% CI 1.16-1.43) in a pooled individual-participant meta-analysis, supporting a biologically plausible mitogenic/cancer concern

    Meta-analysisPMID 26921328 ↗

Last reviewed 2026-07-06 · Verified against PubMed · Educational, not medical advice