IGF-1 LR3
Long R3 Insulin-like Growth Factor 1 — a modified 83-amino-acid analogue of native IGF-1 with an arginine substitution at position 3 and a 13-amino-acid N-terminal extension. These modifications dramatically reduce binding to IGF binding proteins, increasing free bioactive IGF-1 signaling by orders of magnitude. One of the most potent anabolic peptides available, capable of promoting muscle cell hyperplasia (new cell creation) rather than solely hypertrophy.
Typical Dosage
Standard: 20-80 mcg subcutaneous or intramuscular once daily. Often cycled 4-6 weeks on, 4 weeks off. Some protocols use site-specific intramuscular injection into target muscles for localized effects.
Administration
Subcutaneous or intramuscular injection
Mechanism of Action
IGF-1 LR3 is an 83-amino-acid analogue of native IGF-1 (70 amino acids) featuring two critical modifications: an arginine substitution at position 3 (replacing glutamic acid) and a 13-amino-acid N-terminal extension peptide. These modifications dramatically reduce binding affinity for the six IGF binding proteins (IGFBP-1 through IGFBP-6) that normally sequester over 98% of circulating IGF-1, effectively increasing the free, bioactive fraction by orders of magnitude.
Free IGF-1 LR3 binds to the IGF-1 receptor (IGF-1R), a receptor tyrosine kinase structurally similar to the insulin receptor. Receptor activation triggers autophosphorylation and recruitment of insulin receptor substrate (IRS) proteins, activating two major downstream cascades: the PI3K/Akt/mTOR pathway (driving protein synthesis, cell survival, and glucose uptake) and the Ras/MAPK/ERK pathway (promoting cell proliferation and differentiation). The potent activation of mTORC1 through Akt directly stimulates ribosomal protein S6 kinase and inhibits 4E-BP1, dramatically increasing the rate of translation and muscle protein synthesis.
What makes IGF-1 LR3 particularly potent for muscle growth compared to GH or native IGF-1 is its ability to promote muscle cell hyperplasia — the creation of entirely new muscle cells from satellite cell differentiation — rather than solely hypertrophy (enlarging existing cells). IGF-1R signaling in satellite cells activates MyoD and myogenin expression, driving proliferation and fusion into existing myofibers. The 20-30 hour half-life of LR3 (compared to 12-15 minutes for native IGF-1) means sustained receptor activation, continuous anabolic signaling, and significantly greater biological potency per dose. However, this same potency carries risks: strong insulin-like hypoglycemic effects, potential promotion of tumor growth through anti-apoptotic signaling, and possible organ hypertrophy with chronic use.
Regulatory Status
Not FDA approved. Research compound. Mecasermin (native IGF-1) is FDA approved for IGF-1 deficiency. LR3 variant is not approved for any medical use.
Risks & Safety
Common: hypoglycemia (significant insulin-like effects — must eat with dosing), joint pain, headache, jaw and hand growth with prolonged use. Serious: potential promotion of existing tumors through anti-apoptotic IGF-1R signaling, organ hypertrophy (intestinal, cardiac) with chronic use, severe hypoglycemia requiring emergency intervention. Rare: peripheral neuropathy, acromegalic features. Significant safety concerns with long-term use. Not FDA approved.
Research Papers
2Published: January 17, 2026
Abstract
Volumetric muscle loss (VML) resulting from severe extremity injuries in combat remains a significant clinical challenge, particularly in austere environments. Current research emphasizes the development and evaluation of definitive treatments, largely neglecting acute stabilization strategies. To address this unmet need, this study investigated the efficacy of delivering insulin-like growth factor 1 long arginine 3 (IGF1-LR3) via a synthetic in situ forming hydrogel muscle void filler (MVF) to enhance muscle recovery after VML.
Published: November 24, 2025
Abstract
Peripheral nerve injuries lead to significant functional deficits, with no treatment achieving complete recovery. Autologous nerve grafting remains the gold standard, but it is limited by donor site morbidity. Artificial nerve conduits have been developed but have not matched the outcomes of autologous grafts. This study introduces the first-ever decellularized plant-based nerve conduit, fabricated from Alstroemeria stem material, integrated with GelMA, and featuring controlled release of Insulin-like Growth Factor Long Arginine 3 (IGF-1 LR3) for enhanced axonal regeneration. Thirty rats were assigned to six experimental groups (n = 5) and underwent a 1 cm sciatic nerve defect. Regeneration was assessed via gait analysis, electrophysiology, histology, and immunohistochemistry, comparing the decellularized conduit to autologous grafts and commercial conduits. The IGF-1 LR3-controlled releasing decellularized conduit significantly improved axonal regeneration and showed comparable performance to autologous nerve grafts, without inducing systemic toxicity. This novel conduit demonstrates the potential of plant-based biomaterials for effective peripheral nerve repair.
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