IGF-1 LR3, short for Long R3 IGF-1, is an engineered version of insulin-like growth factor 1: the 70-amino-acid human hormone with one amino acid swapped and a 13-amino-acid extension added, built in the early 1990s so it would escape the binding proteins that normally hold IGF-1 in check. Its published record is cell culture and rodent studies, we found no human trial of it, it has no FDA approval, and it is prohibited in sport.
The approved IGF-1 drug, mecasermin, is a different product with a different molecule, and its label is the closest thing to a human safety record for this class.
What it is
IGF-1 is a 70-amino-acid hormone that sits downstream of growth hormone. As the mecasermin label describes it, growth hormone binds its receptor in the liver and other tissues and stimulates IGF-1 production, and IGF-1 is a key mediator of growth. In blood, most IGF-1 is held by six IGF-binding proteins (IGFBPs), with more than 80% bound in a complex with IGFBP-3, which regulates how much reaches tissues.
The analog was designed in Adelaide. Francis and colleagues (Journal of Molecular Endocrinology, 1992) described a family of "Long" IGF-1 fusion peptides, each carrying an extension made from the first 11 amino acids of porcine growth hormone plus two more residues. In the version they called Long [Arg3]-IGF-I, the glutamate at position 3 of human IGF-1 was also replaced with arginine. That is the molecule now sold as IGF-1 LR3, 83 amino acids in all.
The authors described the analogs as reagents for investigating how IGF-1 works. Their design logic was binding-protein evasion: the changes reduce binding to IGFBPs, so more of the molecule stays free to act.
What the cell studies report
In the Francis study, the Long analogs were more potent than natural IGF-1 at stimulating protein and DNA synthesis in rat muscle-precursor cells, and Long [Arg3]-IGF-I was the most potent in cells that secrete IGFBPs. In chicken fibroblasts, which secrete no detectable IGFBPs, it was less potent than natural IGF-1. The authors concluded that its extra potency came from reduced binding-protein interaction, not stronger receptor binding.
That point shapes everything else. IGF-1 LR3 is not a stronger key for the IGF-1 receptor. It is a key that is harder to put away.
What the animal studies report
Rats. Tomas and colleagues (Biochemical Journal, 1992) gave rats the steroid dexamethasone to induce a muscle-wasting state, then added IGF-1 or its analogs for seven days. Natural IGF-1 partly reversed the weight loss and nitrogen loss. The analog LR3IGF-I was about 2.5 times as potent as IGF-1, even though it bound the IGF-1 receptor about three times less well, a result the authors linked to the binding proteins that the steroid treatment raised. IGF-1 and especially the analogs also increased gut weight by up to 45%. A companion study (Read and colleagues, Journal of Endocrinology, 1992) reported marked gut growth in the same rat model. These are short experiments in a drug-induced catabolic state, not models of healthy animals.
Mice. Engel and colleagues (Journal of Alzheimer's Disease, 2025) treated male mice bred to develop Alzheimer's-like amyloid plaques with LR3-IGF-1 for seven months. Body composition improved and some plaque features changed in the cortex, but the treatment did not preserve memory or behavior on multiple tests. The authors did not support it as a single therapy.
The human record
We found no published human trial of IGF-1 LR3. A 2026 review in Frontiers in Endocrinology (Dominikowski and colleagues) lists it among the growth-hormone-axis peptides marketed as "research compounds," and describes reported adverse effects across that group, including disturbances of blood sugar, fluid retention and musculoskeletal symptoms, along with biologically plausible but unproven concerns about growth of abnormal cells. Those are observations about a class used outside trials, not findings from a study of IGF-1 LR3.
The approved IGF-1 drug, and why it is not the same
Mecasermin, recombinant human IGF-1 sold as Increlex, has been approved since August 30, 2005. It is natural-sequence IGF-1, not LR3, and its current label limits it to growth failure in children aged 2 and older with severe primary IGF-1 deficiency, or with growth hormone gene deletion and neutralizing antibodies to growth hormone.
The label is useful here only as a record of what IGF-1 receptor activation did in the population that was studied. It warns of severe hypoglycemia, including hypoglycemic seizures, because IGF-1 has insulin-like effects. It also warns of hypersensitivity reactions including anaphylaxis, increased pressure inside the skull, tonsil and adenoid enlargement, and slipped growth plates at the hip. It lists malignant neoplasia as a contraindication and states that several cases of malignant neoplasia have been observed in children treated with it. None of that can be transferred directly to an analog designed to be more potent and less regulated by binding proteins; it marks the questions a human study of IGF-1 LR3 would have to answer.
Regulatory status
FDA approval. None. No IGF-1 LR3 product is approved for any use.
How it would be regulated. Under a rule that took effect in March 2020, the FDA treats an amino acid chain longer than 40 residues as a protein regulated as a biological product. At 83 amino acids, IGF-1 LR3 is on the protein side of that line, as is mecasermin, which Drugs@FDA lists as a biologics license.
Compounding. IGF-1 LR3 does not appear on the FDA's 503A category lists for nominated bulk substances, as updated May 14, 2026.
Sport. The World Anti-Doping Agency's 2026 Prohibited List bans, at all times, "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues" under section S2.3. IGF-1 LR3 is an analog of IGF-1.
For how IGF-1 LR3 fits with the secretagogues that act upstream of it, see our review of the growth-hormone axis and tesamorelin vs sermorelin.
Frequently asked questions
What is IGF-1 LR3?
An engineered analog of IGF-1 with an arginine at position 3 and a 13-amino-acid extension, 83 amino acids in total, designed to bind poorly to IGF-binding proteins.
Is IGF-1 LR3 the same as IGF-1?
No. Natural IGF-1 is 70 amino acids and is bound by IGFBPs. IGF-1 LR3 is a longer, modified molecule that evades most of that binding, and it was less potent than IGF-1 in cells without binding proteins.
Has IGF-1 LR3 been tested in humans?
We found no published human trial. Its record is cell culture, rat and mouse studies.
Is IGF-1 LR3 FDA-approved?
No. The approved IGF-1 drug is mecasermin (Increlex), a different molecule approved only for specific pediatric growth disorders.
Is IGF-1 LR3 banned in sport?
Yes. WADA prohibits IGF-1 and its analogues at all times under S2.
Sources:
- Francis et al., J Mol Endocrinol, 1992 (design of Long IGF-I analogs; cell studies)
- Tomas et al., Biochem J, 1992 (dexamethasone-treated rats)
- Read et al., J Endocrinol, 1992 (gut growth in dexamethasone-treated rats)
- Engel et al., J Alzheimers Dis, 2025 (LR3-IGF-1 in 5XFAD mice)
- Dominikowski et al., Front Endocrinol, 2026 (review of GH-axis peptides sold as research compounds)
- Increlex (mecasermin) prescribing information, DailyMed, 2026
- Drugs@FDA, Increlex (mecasermin), application 021839
- FDA, final rule: Definition of the Term "Biological Product," Federal Register, February 21, 2020
- FDA, Bulk drug substances nominated for use in compounding under section 503A (category lists, updated May 14, 2026)
- WADA 2026 Prohibited List, as published in the Dutch treaty series (S2.3)
No compound discussed in this review is FDA-approved apart from mecasermin, a different molecule. Nothing above is dosing guidance or a treatment claim. Research use only.
For research use only · Not for human or veterinary use · No research compound discussed here is FDA-approved for any indication