Igf-1 lr3

Igf-1 lr3 is a modified, longer-lasting version of insulin-like growth factor-1 (IGF-1), the hormone that drives tissue and muscle growth, and it's pursued mainly for muscle growth. It's engineered to resist being cleared by binding proteins in the blood, making it more potent and longer-lasting than the natural hormone. It's not FDA-approved and was never submitted for approval, so it's sold only as a research peptide. It's a different compound from mecasermin (Increlex), the FDA-approved native form of IGF-1 used for a rare childhood condition, and raising IGF-1 chronically also carries a theoretical cancer-risk concern and can cause dangerously low blood sugar.

Igf-1 lr3, a long-acting form of IGF-1, has been studied for muscle growth, mostly in animal and cell studies that showed it is more potent and longer-lasting than native IGF-1. There are essentially no controlled human trials of igf-1 lr3 itself. Separately, large observational studies have linked higher circulating IGF-1 to increased risk of certain cancers, so chronic use carries a theoretical cancer-risk concern, and IGF-1 can also lower blood sugar, creating a hypoglycemia risk.

Not FDA-approved for any indication. Mecasermin (Increlex), the recombinant native unmodified IGF-1, IS FDA-approved (BLA 021839, originally approved August 30, 2005) for treatment of growth failure in pediatric patients ≥2 years with severe primary IGF-1 deficiency or with growth hormone gene deletion who have developed neutralizing antibodies to GH.[¹] igf-1 lr3 (the modified analog) has never been FDA-approved for any indication and has never been advanced through FDA nda review. Available only as a research peptide and as a recombinant-protein research reagent (LONG®R3 igf-I from GroPep/Repligen for cell-culture applications). Use in humans is off-label and outside any FDA-recognized supply chain. Not DEA-scheduled. WADA-banned in regulated sport — explicitly covered under Section S2.3 (Growth Factors and Growth Factor Modulators) of the 2026 Prohibited List via the named-substance line *"Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues"* — the "and its analogues" wording unambiguously covers igf-1 lr3.[⁶]

Igf-1 lr3 is not FDA-approved and is banned in regulated sport (WADA); its safety in humans has not been established in clinical trials. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ For research and educational purposes only. Igf-1 lr3 (Long-R3 IGF-1) is not approved by the FDA for any indication. The native unmodified IGF-1 form (mecasermin / Increlex) IS FDA-approved for a narrow pediatric indication — but igf-1 lr3 is a structurally modified analog with substantially different pharmacokinetics and is not the same compound. Information in this entry is informational, not medical advice. Always confirm dose calculations with the in-app calculator and consult appropriate professional guidance before any protocol decisions.

⚠️ Precision matters at low doses. Igf-1 lr3 is dosed in micrograms (mcg), not milligrams. Typical research-community doses ( per dose) at typical reconstitution concentrations ( vial / 1 mL BAC water = =/unit on a U-100 syringe) produce small draws in the range — a precision-friendly range comparable to BPC-157 and GHK-cu. Higher concentrations ( / 0.5 mL =) produce smaller draws where one-unit precision matters more. Always verify draws against the in-app calculator. A separate acute-precision concern: Igf-1 lr3 is the most acutely-hazardous compound in this library for dosing errors — overdose can produce severe hypoglycemia within hours of injection. See safety callout below.

⚠️ igf-1 lr3 is not the same compound as mecasermin (Increlex). Despite both being recombinant IGF-1-based compounds, these are structurally and regulatorily distinct: - Mecasermin (Increlex) = recombinant native unmodified IGF-1, identical 70-amino-acid sequence to endogenous human IGF-1. FDA-approved (BLA 021839, August 30, 2005) for severe primary IGF-1 deficiency in pediatric patients ≥2 years. Manufactured under FDA-approved framework (originally Tercica, now Ipsen). Available by prescription through standard pharmacy channels for the FDA-approved indication; sometimes used off-label. - igf-1 lr3 (this entry) = modified 83-amino-acid analog with Glu→Arg substitution at position 3 plus a 13-amino-acid N-terminal extension. The modifications produce ~100-fold reduced binding to IGFBPs (the binding proteins that normally sequester IGF-1 in plasma), ~20–30 hour half-life vs ~12-15 hours for IGFBP-3-bound native IGF-1, and ~3x increased potency. Originally developed by GroPep (now Repligen) as LONG®R3 igf-I for cell-culture applications — the IGFBP-binding-evasion makes it a more stable additive for recombinant protein production. Not FDA-approved for any indication; never advanced through FDA nda review. Available only as a research peptide and as a recombinant-protein research reagent. Researchers using igf-1 lr3 from research-peptide supply chains are using the modified analog, not the FDA-approved Increlex product. The pharmacokinetic profile, side-effect pattern, and supply-chain quality are not equivalent. The mecasermin clinical-trial safety data does not directly extrapolate to igf-1 lr3 because the IGFBP-binding-evasion that defines LR3 produces a substantially different in-vivo exposure profile than the IGFBP-bound native IGF-1 that mecasermin produces.

⚠️ Hypoglycemia is the acute safety concern. Theoretical cancer risk is the chronic safety concern. Two distinct safety considerations apply: Acute hypoglycemia (the dosing-error / fasted-state risk): IGF-1 binds the IGF-1 receptor and (with lower affinity) the insulin receptor; both produce glucose-uptake-promoting effects. In a fasted state or with high doses, igf-1 lr3 can produce severe hypoglycemia within hours of injection. Symptoms include lightheadedness, shakiness, sweating, blurred vision, mental confusion, and (severe) loss of consciousness or seizure. Mitigation: (a) inject within 30–60 minutes of a carbohydrate-containing meal; (b) avoid fasted-state injection until the user knows their individual tolerance; (c) keep fast-acting carbohydrate (glucose tablets, juice) accessible during the immediate post-injection period; (d) start at low doses ( or below) for the first several injections to establish tolerance. Chronic theoretical cancer risk (the IGF-1-axis-elevation concern): Multiple large observational studies — UK Biobank (394,388 cancer-free participants), EPIC-Heidelberg (a case-cohort analysis of 7,461 serum samples), and Mendelian randomization studies — consistently associate elevated circulating IGF-1 with increased risk of colorectal, breast (premenopausal), and prostate cancers.[⁵][⁷] Mendelian randomization (which provides stronger causal inference than observational association) supports a causal role for IGF-1 in colorectal cancer specifically. Any compound that elevates IGF-1 axis activity carries this theoretical risk. Researchers using igf-1 lr3 chronically (vs short-cycle use) should be explicit with themselves about this risk, particularly with personal or family history of these cancers. The EPIC-Heidelberg cohort additionally reported a U-shaped relationship between IGF-1 and all-cause mortality — both very-low and very-high IGF-1 are associated with elevated mortality risk, with the highest IGF-1 quintile carrying meaningful excess hazard.[⁷]

⚠️ WADA-banned in regulated sport — explicitly named under Section S2.3 (Growth Factors and Growth Factor Modulators) via "and its analogues" wording. The canonical WADA 2026 Prohibited List Section S2.3 names *"Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues"* alongside fibroblast growth factors (FGFs), hepatocyte growth factor (HGF), mechano growth factors (MGFs), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and (in the same S2.3 section) thymosin-β4 derivatives.[⁶] igf-1 lr3 is unambiguously covered by the "and its analogues" wording — the LR3 modifications produce a structural analog of IGF-1, and the WADA framework explicitly captures structurally-modified analogs of named substances. The S2.3 catch-all clause additionally covers *"other growth factors or growth factor modulators affecting muscle, tendon or ligament protein synthesis/degradation, vascularisation, energy utilization, regenerative capacity or fibre type switching"* — igf-1 lr3's anabolic and tissue-growth effects fall directly within this clause. Prohibited at all times — in-competition and out-of-competition. This is the second S2.3 listing in the library alongside TB-500/thymosin-β4 derivatives.

Igf-1 lr3 is a modified analog of recombinant human IGF-1 designed to evade IGF-binding protein (IGFBP) sequestration. The compound was originally developed by GroPep (later acquired by Repligen) as LONG®R3 igf-I for cell-culture applications — IGFBP-binding-evasion makes it a more stable additive for recombinant protein production than native IGF-1, which is rapidly bound and inactivated by IGFBPs in serum-containing culture media. The structural modifications:

- Glu→Arg substitution at position 3 ("R3") — disrupts a critical IGF-1/IGFBP contact point, reducing IGFBP binding affinity by ~100-fold for most IGFBPs - 13-amino-acid N-terminal extension (MFPAMPLLSLFVN, the "Long" component) — further reduces IGFBP binding and increases plasma stability

The combined effect: Igf-1 lr3 has approximately 3x the potency of native IGF-1 in receptor-binding assays and a substantially extended half-life (~20–30 hours vs ~10 minutes for unbound native IGF-1).[³]

Mechanism. Igf-1 lr3 binds the IGF-1 receptor (IGF-1R) with affinity comparable to native IGF-1, with lower-affinity binding to the insulin receptor (the source of the hypoglycemia risk). The downstream signaling cascade is the same as native IGF-1 — primarily PI3K/Akt/mTOR for growth, anti-apoptosis, and anabolic effects, plus MAPK/ERK for proliferative effects. The mechanism difference between igf-1 lr3 and native IGF-1 is purely IGFBP-binding-evasion-driven bioavailability — neither receptor-target nor downstream-signaling differs. Igf-1 lr3 produces the same biological effects as native IGF-1 but at substantially extended exposure duration and free-fraction availability.

The mecasermin / Increlex relationship. Mecasermin (Increlex, BLA 021839) is recombinant native unmodified IGF-1 — identical 70-amino-acid sequence to endogenous human IGF-1. It was FDA-approved on August 30, 2005, originally manufactured by Tercica (now Ipsen), for treatment of growth failure in pediatric patients ≥2 years with severe primary IGF-1 deficiency (height SDS ≤ -3.0 and basal igf-1 sds ≤ -3.0 with normal or elevated GH) or with GH gene deletion who have developed neutralizing antibodies to GH.[¹] Mecasermin is the FDA-approved recombinant IGF-1 product; igf-1 lr3 is the modified-analog research compound. They share a receptor target and core biology but are not interchangeable in pharmacokinetics, supply chain, or regulatory framework. Researchers using mecasermin off-label for adult anti-aging or anabolic use cases are using a different compound than researchers using igf-1 lr3 from research-peptide supply chains.

Regulatory status (US — current). Igf-1 lr3 is not FDA-approved for any indication and has never been advanced through FDA nda review. It is not legally compoundable through US 503A pharmacies (the compound is not on the 503A bulks list and, per the broader peptide-bulks-list situation, is not approved for compounding). All US use of igf-1 lr3 is through unregulated research-peptide supply chains, with substantial variability in product purity and potency. Not DEA-scheduled. Note the regulatory distinction: mecasermin (Increlex) is FDA-approved and prescribable; igf-1 lr3 is not. Researchers conflate these compounds at their regulatory peril.

Regulatory status (sport — WADA). Igf-1 lr3 is WADA-banned under Section S2.3 (Growth Factors and Growth Factor Modulators) of the 2026 Prohibited List via the named-substance line "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues."[⁶] The S2.3 catch-all clause additionally covers compounds with anabolic, tissue-growth, or vascularization effects on muscle/tendon/ligament. Both lines unambiguously cover igf-1 lr3. Prohibited at all times.

Common research interests. Despite the regulatory status, igf-1 lr3 is among the most-used research peptides in the bodybuilding-research-community context, primarily for: - Anabolic / muscle growth — the dominant research-community use case. Often combined with GH-axis peptides (CJC-1295/Ipamorelin) or with exogenous testosterone in supraphysiologic-cycle contexts. - Recovery from training — accelerated recovery between training sessions, primarily through IGF-1's effects on muscle protein synthesis and satellite cell activation. - "Site-specific muscle growth" (largely unsupported by evidence) — the hypothesis that intramuscular administration at a target muscle produces preferential growth at that muscle. The hypothesis is not supported by human pharmacokinetic data; igf-1 lr3's systemic distribution and IGFBP-evasion make local accumulation unlikely. - Adjunct in injury recovery — overlap with the BPC-157/TB-500 use cases though through a different mechanism (anabolic vs. angiogenic/regenerative). - Off-label adult anti-aging / longevity — a controversial use case given the chronic-elevated-IGF-1 cancer-risk evidence base. Researchers using igf-1 lr3 chronically for longevity goals are operating against the body of evidence linking elevated IGF-1 to increased cancer risk.

The cancer-axis question (load-bearing safety detail). Multiple large observational studies and a Mendelian randomization analysis support a meaningful association between elevated circulating IGF-1 and increased cancer risk — particularly colorectal, premenopausal breast, and prostate cancers.[⁵] In the UK Biobank analysis of ~400,000 participants, higher circulating IGF-1 was associated with increased risk of colorectal, breast, prostate, and thyroid cancers, with hazard ratios reported per 5 nmol/L increment in IGF-1.[⁵] The EPIC-Heidelberg case-cohort analysis (7,461 serum samples; subcohort 1,810 men and 1,890 women) found a U-shaped mortality relationship — both very-low and very-high IGF-1 are associated with elevated mortality.[⁷] Mendelian randomization (which provides stronger causal inference) supports a causal role specifically for colorectal cancer. Any compound that chronically elevates IGF-1 axis activity carries this theoretical risk — this includes igf-1 lr3, native mecasermin used off-label, and (to a lesser, indirect extent) GH-secretagogue peptides that elevate endogenous IGF-1. Researchers should weigh this risk explicitly when considering chronic vs short-cycle igf-1 lr3 use.

Commonly reported

• Hypoglycemia — see safety callout. Fasted-state injection or high doses substantially increase risk. Requires fast-acting carbohydrate accessibility.
• Injection site reaction — uncommon at typical doses; more common with IM injection
• Muscle pump / vascularity — commonly reported as a desired effect
• Joint pain, fluid retention — common; typically mild-to-moderate
• Numbness or tingling in extremities — uncommon; suggests nerve-axis involvement; warrants dose reduction
• Carpal tunnel syndrome — uncommon but characteristic of GH-axis / IGF-1-axis activation; warrants dose reduction or discontinuation if symptomatic
• Insulin resistance — a documented effect of sustained IGF-1 axis elevation; warrants HbA1c monitoring
• Soft tissue thickening (acromegaly-like changes in extremities) — uncommon at typical research-community doses, more commonly described in long-term high-dose use
• Theoretical cancer risk — see safety callout. Multiple large observational studies + Mendelian randomization support an association between elevated IGF-1 and colorectal/breast/prostate cancer risk.[⁵][⁷]
• Cardiovascular concerns — the EPIC-Heidelberg case-cohort analysis identified a U-shaped mortality relationship, with both very-low and very-high IGF-1 associated with elevated cardiovascular and all-cause mortality.[⁷]

Serious

• Severe hypoglycemia — loss of consciousness, seizure, mental confusion not reversed by glucose
• Acute carpal tunnel symptoms
• New mass or symptoms suspicious for malignancy
• Acute peripheral edema or signs of fluid overload

Active malignancy — absolute contraindication

Active hyperinsulinemia, prediabetes, or diabetes — caution; hypoglycemia risk is elevated

Personal or family history of cancers with IGF-1-axis sensitivity (colorectal, premenopausal breast, prostate) — caution; chronic igf-1 lr3 use raises a theoretical risk concern

Pregnancy and lactation — no human data; default to contraindicated

Pediatric use — no data for igf-1 lr3 specifically; mecasermin (Increlex) has FDA-approved pediatric indication for severe primary IGF-1 deficiency only

Active liver dysfunction — igf-1 lr3 is hepatically processed; severe impairment warrants caution

Active anabolic-steroid cycle without medical supervision — combined anabolic load is poorly characterized

Concurrent insulin — high acute-hypoglycemia risk (see Common Stacks)

Regulatory note (US): Igf-1 lr3 is not FDA-approved for any indication. Mecasermin (Increlex) IS FDA-approved for severe primary IGF-1 deficiency in pediatric patients only. All adult use and all igf-1 lr3 use is off-label or outside FDA approval.

Regulatory note (sport): WADA-banned under Section S2.3 of the 2026 Prohibited List via "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues" wording.[⁶]

Not DEA-scheduled.

Peptide

A short chain of amino acids, the building blocks of proteins. Many compounds in this library are peptides.

IGF-1

a growth factor the liver makes in response to growth hormone; used as a lab marker (and, for igf-1 lr3, a growth factor that drives tissue and muscle growth).

Hypoglycemia

abnormally low blood sugar, which can cause shakiness, confusion, or worse.

Preclinical

Research done in cells or animals, before human clinical trials. Promising preclinical results don't always hold up in people.

WADA Prohibited List

The list of substances banned in regulated sport by the World Anti-Doping Agency.

1. Ipsen Pharma (originally Tercica). Increlex (mecasermin) injection prescribing information. US Food and Drug Administration. BLA 021839, originally approved August 30, 2005. Most recent label revision (s033) accessible at accessdata.fda.gov/drugsatfda_docs/label/2025/021839s033lbl.pdf.
2. Tomas FM, Knowles SE, Owens PC, Chandler CS, Francis GL, Read LC, Ballard FJ. (1992). Insulin-like growth factor-I (igf-I) and especially igf-I variants are anabolic in dexamethasone-treated rats. Biochemical Journal, 282(Pt 1):91–97 (February 15, 1992).(PMID 1371669)
3. Francis GL, Ross M, Ballard FJ, Milner SJ, Senn C, McNeil KA, Wallace JC, King R, Wells JR. (1992). 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. Journal of Molecular Endocrinology, 8(3):213–223. (Citation candidate for the foundational lr3 igfbp-binding-evasion characterization; the Francis et al. publication established the ~100-fold reduced IGFBP affinity that defines the LR3 pharmacology.) Source for: ~100-fold reduced IGFBP binding affinity of Long-R3 IGF-1 vs native IGF-1; the structural basis for the LR3 modification's enhanced potency; ~3x potency advantage in receptor-binding assays.(PMID 1378742)
4. Tomas FM, Lemmey AB, Read LC, Ballard FJ. (1996). Superior potency of infused igf-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection. Journal of Endocrinology, 150(1):77–84. (Citation candidate for the in-vivo lr3 pk/PD evidence base.) Source for: in-vivo demonstration that lr3 igf-1's IGFBP-binding-evasion produces superior anabolic potency vs native IGF-1 even with bolus subcutaneous administration; the basis for LR3's research-community use case.(PMID 8708565)
5. Knuppel A, Fensom GK, Watts EL, Gunter MJ, Murphy N, Papier K, Perez-Cornago A, Schmidt JA, Smith Byrne K, Travis RC, Key TJ. (2020). Circulating Insulin-like Growth Factor-I Concentrations and Risk of 30 Cancers: Prospective Analyses in UK Biobank. Cancer Research, 80(18):4014–4021 (September 15, 2020; Epub July 24, 2020).(PMID 32709735)
6. World Anti-Doping Agency. The 2026 Prohibited List, International Standard (effective 1 January 2026). Canonical PDF: wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf (linked from the WADA landing page; local archival copy in `docs/legal/wada-2026-prohibited-list.pdf`). Igf-1 lr3 is named explicitly under Section S2.3 (Growth Factors and Growth Factor Modulators) — page 8 of the canonical PDF — via the named-substance line "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues." Verbatim from the canonical PDF (line 509): "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues" — listed alongside Fibroblast growth factors (FGFs), Hepatocyte growth factor (HGF), Mechano growth factors (MGFs), Platelet-derived growth factor (PDGF), Vascular endothelial growth factor (VEGF), and (in the same S2.3 section at line 521) "Thymosin-ß4 and its derivatives e.g. TB-500." The S2.3 catch-all clause additionally covers "other growth factors or growth factor modulators affecting muscle, tendon or ligament protein synthesis/degradation, vascularisation, energy utilization, regenerative capacity or fibre type switching" — igf-1 lr3's anabolic and tissue-growth effects fall directly within this clause. Prohibited at all times.
7. Mukama T, Srour B, Johnson T, Katzke V, Kaaks R. (2023). IGF-1 and Risk of Morbidity and Mortality From Cancer, Cardiovascular Diseases, and All Causes in EPIC-Heidelberg. The Journal of Clinical Endocrinology & Metabolism, 108(10):e1092–e1105 (September 18, 2023).(PMID 37066827)

• Testosterone — discussed together in this entry's stacks section
• BPC-157 / TB-500 Blend — discussed together in this entry's stacks section
• AOD-9604 — same mechanism class
• HGH (Human Growth Hormone) / Somatropin — same mechanism class
• MGF — same mechanism class
• ACE-031 — shared research area