IGF-1 LR3
Long R3 IGF-1 · IGF-1 Long Arg3 · LR3 IGF-1
Long-acting IGF-1 analog (~3× the potency of native IGF-1) acting at the downstream effector end of the GH axis
Overview
IGF-1 LR3 (Long R3 IGF-1) is an 83-amino-acid analog of insulin-like growth factor 1 — the principal anabolic mediator the liver produces in response to growth hormone. It differs from the native 70-residue hormone in two ways: an arginine substitution at position 3 and a 13-amino-acid N-terminal extension. Together these sharply reduce its affinity for the IGF-binding proteins that normally sequester circulating IGF-1, so a much larger fraction stays free and active and its functional duration is greatly extended. Reported potency is on the order of three times that of equimolar native IGF-1.
Unlike the GH secretagogues in this category, IGF-1 LR3 does not prompt the pituitary to release growth hormone — it is the downstream effector itself, binding the IGF-1 receptor on muscle, bone, liver, nerve, and connective tissue to drive protein synthesis, cell proliferation, and glucose uptake through the PI3K/Akt/mTOR and RAS/RAF/MEK/ERK pathways. Its half-life is reported at roughly 20–30 hours, far longer than native IGF-1 (about 12–15 hours), which is why community protocols dose it once daily. Because the IGF-1 receptor shares signaling with the insulin receptor, the dominant practical hazard is hypoglycemia.
There are no published human clinical trials of IGF-1 LR3 specifically; the human safety reference point is native IGF-1 (mecasermin/Increlex), where hypoglycemia was common, and the efficacy reference is preclinical rodent work. Two features warrant particular caution: IGF signaling is mitogenic and anti-apoptotic, raising a theoretical cancer concern that makes a cancer history a contraindication; and the hypoglycemia risk is additive with insulin. The figures below summarize that reference data and widely-reported community practice and are an educational research reference only, not medical advice.
Key parameters
- Dose range
- 20–100 mcg daily (community)
- Frequency
- Once daily
- Half-life
- ~20–30 hours
- Route
- Subcutaneous
- Vial sizes
- 1 mg
- Regulatory status
- Not approved for human use by the FDA or EMA (only native IGF-1, mecasermin/Increlex, is approved, and only for pediatric severe primary IGF-1 deficiency). Sold as research material only and prohibited in sport by WADA at all times under section S2.
Mechanism of action
IGF-1 receptor agonism
Activates the IGF-1 receptor across muscle, bone, liver, nerve, and connective tissue to drive the cellular growth, proliferation, and protein synthesis normally produced downstream of growth hormone.
PI3K → Akt → mTOR signaling
Engages the metabolic/anabolic arm of IGF signaling, promoting protein synthesis and glucose uptake — the latter underlying its insulin-like blood-glucose-lowering and hypoglycemia risk.
RAS → RAF → MEK → ERK signaling
Drives the proliferative arm of IGF signaling (cell growth and division); because this pathway is mitogenic, it is also the basis of the theoretical cancer concern with sustained IGF-1 elevation.
Reduced IGFBP binding (extended free fraction)
The Arg3 substitution and N-terminal extension lower affinity for IGF-binding proteins, leaving more unbound, active peptide in circulation and extending the half-life to roughly 20–30 hours.
Dosing protocol & phases
| Phase | Weeks | Dose | Notes |
|---|---|---|---|
| Assessment | Days 1–7 | ~20 mcg once daily | Low starting dose to gauge tolerance; hypoglycemic symptoms are most likely in the first weeks. Community-derived, not clinically established. |
| Working range | Weeks 2–4 | 40–80 mcg once daily | Most commonly cited band; women often stay lower (~10–20 mcg). Dosed with food, never fasted. |
| Cycle ceiling | Up to ~4–6 weeks on, then off | Up to 100 mcg once daily | Cycles are commonly capped near 4–6 weeks because of insulin resistance, organ-growth, and receptor-desensitization concerns, with an equal or longer off period. |
Reconstitution guide
For educational and research reference only. Not intended for human consumption, not medical advice. Compounds discussed are sold and used for laboratory research purposes only.
1 mg vial + 2 mL bacteriostatic water
Concentration500 mcg/mL · 0.5 mg/mL
| Target dose | Draw volume | U-100 units |
|---|---|---|
| 20 mcg | 0.04 mL | 4 |
| 40 mcg | 0.08 mL | 8 |
| 80 mcg | 0.16 mL | 16 |
| 100 mcg | 0.2 mL | 20 |
A 1 mg vial in 2 mL gives 500 mcg/mL, keeping a 20 mcg dose at 0.04 mL (4 units) and 100 mcg at 0.2 mL (20 units). Note: some suppliers advise a low-acidity diluent rather than plain bacteriostatic water — follow the product's reconstitution guidance.
Reconstitution calculator
Pre-filled with IGF-1 LR3's vial sizes. Adjust the water volume and target dose to see the exact draw, with warnings for doses that are hard to measure or won't fit a syringe.
At 500 micrograms per millilitre, a 20 microgram dose is 0.04 millilitres, or 4 units on a U-100 syringe, giving 50 doses per vial.
This draw is only 4 units — small volumes are hard to measure accurately. Consider using less bacteriostatic water to make each dose a larger, easier-to-read draw.
Supplies needed
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Recommended supply
IGF-1 LR3 — research vial
From our verified partner Dynotides, with a third-party certificate of analysis per batch.
Injection supplies
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Bacteriostatic water
Diluent for reconstituting lyophilized vials.
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Insulin syringes (U-100)
0.3–0.5 mL, 29–31 G for accurate small draws.
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Alcohol prep pads
Sterile swabs for the vial stopper and site.
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Sharps container
Safe disposal of used needles.
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Storage fridge
Keeps reconstituted vials at 2–8 °C.
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Insulated travel case
Cooled, TSA-friendly case for travel.
Missed-dose guidance
With a 20–30 hour half-life a missed dose can be taken later the same day if remembered, but it is otherwise skipped — doses are never doubled. Crucially, IGF-1 LR3 is taken with food and never close to bedtime, because overnight hypoglycemia is hard to detect; a dose missed near bedtime is better skipped than taken late.
Side effects & safety
| Category | Effect | Trial incidence |
|---|---|---|
| Metabolic | Hypoglycemia (low blood sugar)Reported in ~42% of patients (30 of 71) in the native-IGF-1 Increlex pediatric program — the closest human reference; the dominant practical hazard, and additive with insulin. | 42% |
| Metabolic | Severe hypoglycemia (requiring assistance or with seizure)A small number of Increlex subjects had severe events including seizures or loss of consciousness; why IGF-1 analogs are not dosed fasted or near bedtime. | — |
| Fluid balance | Fluid retention and joint discomfortCommonly reported, consistent with IGF/GH-axis activity. | — |
| Oncologic | Theoretical cancer-promotion riskIGF signaling is mitogenic and anti-apoptotic; rodent studies of native IGF-1 showed increased tumor incidence, making a personal or strong family cancer history a contraindication. | — |
| Lymphoid | Tonsillar / lymphoid hypertrophyReported in roughly 15% of Increlex-treated children. | 15% |
| Injection site | Lipohypertrophy or local irritationRotate sites and avoid reusing the same spot within about a week. | — |
Clinical trials & evidence
No human trials of IGF-1 LR3 (mecasermin/Increlex as reference)
Reference (native IGF-1)Mean ~3.9 years (up to 11.5 years) · 71 children with severe primary IGF-1 deficiency
There are no published human trials of IGF-1 LR3 itself; the closest human data come from native rhIGF-1 (Increlex), where hypoglycemia (~42%) and lymphoid hypertrophy were the notable adverse events.
Trial identifier needs verification
Tomas et al. preclinical potency / safety
Preclinical (rodent)Varies · Rats (including tumor-bearing catabolic models)
IGF-1 LR3 was roughly 1.5–2× more potent than equimolar native IGF-1 for anabolic endpoints, but a companion study showed it increased tumor growth in tumor-bearing catabolic rats — reinforcing the mitogenic concern.
Trial identifier needs verification
Storage & handling
- Lyophilized
- Store the lyophilized powder frozen at −20 °C for long-term stability (about 12 months) or refrigerated at 2–8 °C for shorter periods, protected from light; brief room-temperature excursions during shipping are tolerated.
- Reconstituted
- After reconstitution, refrigerate at 2–8 °C and use within roughly 28–30 days. Do not freeze the reconstituted solution, as freeze-thaw cycles degrade the peptide; discard if it becomes cloudy.
Comparisons
| Vs. | Target | Half-life | Dosing | Efficacy | Status |
|---|---|---|---|---|---|
| IGF-1 DES(1-3) | IGF-1 receptor (both) | ~20–30 h vs ~20–30 min | Once daily vs 2–3× daily | Systemic, long-acting vs very short, highly localized action | Both not approved |
| Mecasermin (Increlex) | IGF-1 receptor (both) | ~20–30 h vs ~5.8 h | Once daily vs twice daily | Long-acting analog (~3× potency) vs FDA-approved native rhIGF-1 for pediatric IGFD | Research-only vs FDA-approved (pediatric IGFD only) |
| Ipamorelin | IGF-1 receptor vs ghrelin/GHS-R | ~20–30 h vs ~2 h | Daily (both) | Acts downstream as the effector itself vs stimulating the pituitary to release GH | Both research-only |
Sources & references
- [1]FDA Prescribing Information — Increlex (mecasermin) injection (native rhIGF-1 reference safety data). ↗ source
- [2]Tomas FM et al. Anabolic effects of insulin-like growth factor-I (IGF-I) and an IGF-I variant (LR3-IGF-I) in rats. PubMed. ↗ source
- [3]Mongongu C et al. Detection of LongR3-IGF-I for anti-doping purposes (validated assay, 2020). ↗ source
Frequently asked questions
How is IGF-1 LR3 different from a GH secretagogue?
Secretagogues like ipamorelin or CJC-1295 prompt the pituitary to release growth hormone, which then raises IGF-1 indirectly. IGF-1 LR3 is the IGF-1 effector itself, in a long-acting form — it engages the IGF-1 receptor directly at the downstream end of the axis rather than triggering any GH release.
Why is hypoglycemia such a concern?
The IGF-1 receptor shares signaling with the insulin receptor, so IGF-1 LR3 lowers blood glucose. In the native-IGF-1 (Increlex) program hypoglycemia affected about 42% of patients, with some severe events. This is why it is taken with food, paired with fast-acting carbohydrate, never dosed fasted or near bedtime, and is an absolute contraindication alongside insulin.
Is IGF-1 LR3 approved or tested in humans?
No. There are no published human trials of IGF-1 LR3 specifically; it is research-grade material, banned in sport by WADA, and the only related approved product is native IGF-1 (mecasermin) for a narrow pediatric indication. Because IGF signaling is mitogenic, a cancer history is a contraindication.
Related protocols
Ipamorelin
NNC 26-0161
Selective GH pulse with minimal cortisol or prolactin effect
Tesamorelin
Egrifta
~−15–18% visceral adipose tissue at 26 weeks (pivotal trials)
Looking to match this protocol to a verified research vial? Our partner supplier publishes a certificate of analysis per batch.
For educational and research reference only. Not intended for human consumption, not medical advice. Compounds discussed are sold and used for laboratory research purposes only.