What it is
IGF-1 (insulin-like growth factor 1) is a natural hormone. The body makes it mostly in the liver. It is made when growth hormone goes up. It tells cells to grow and divide. In the blood, most IGF-1 is held by carrier proteins called binding proteins. These control how much IGF-1 is free to work.
IGF-1 LR3 is a man-made version. One building block near the start is swapped. An arginine takes the place of a glutamate. Also, 13 extra building blocks from pig growth hormone are added to the front. Because of these changes, it mostly slips past the binding proteins.
Bacteria are used to make it. It is sold mainly as an ingredient that helps cells grow. It is used in labs and in large factory tanks (bioreactors). It is not an approved medicine. It is also not mecasermin. Mecasermin is the approved drug that is the same as natural IGF-1.
LR3-IGF-I is an 83-residue single-chain protein: Met1-porcine GH(1–11)-Val-Asn fused to human IGF-I(1–70) carrying a Glu3→Arg substitution (FDA UNII M9L22Y19H9), about 9.1 kDa. It acts on the IGF-1 receptor, a receptor tyrosine kinase, and in H35 hepatoma cells, which respond through the insulin receptor, it kept a potency relative to IGF-I similar to that seen in myoblasts (Francis 1992).
Its affinity for IGFBP-3, IGFBP-4 and total rat plasma IGFBPs is roughly 1,000-fold lower than that of IGF-I. That, not stronger receptor binding, explains its potency: it was 5–10 times more potent than IGF-I in L6 myoblasts, which secrete IGFBPs, but less potent than IGF-I in chicken embryo fibroblasts, which do not. Escaping IGFBPs also means faster removal: in rats it was cleared from plasma much more rapidly than IGF-I (Ballard 1993). No human pharmacokinetic data exist.
Mecasermin, by contrast, is the unmodified 70-residue human IGF-1 (7,649 Da); its label reports that over 80% circulates bound to IGFBP-3 and the acid-labile subunit, with a terminal half-life of 5.8 hours in children with severe primary IGF-1 deficiency.
Who made it and when
IGF-1 LR3 came from growth research in Adelaide, Australia. This work took place in the late 1980s and early 1990s. Three groups took part. One was CSIRO, Australia’s national science agency. Another was a government-backed research centre on tissue growth and repair. The third was a local company called GroPep.
The researchers thought binding proteins in the blood were weakening IGF-1 given as a treatment. So they built versions made to escape them. The short piece of pig growth hormone at the front also helped. It helped bacteria fold the protein the right way.
GroPep patented the design. It sold the long Arg3 version as an ingredient for growing cells. GroPep later became part of Novozymes. No effort to turn IGF-1 LR3 into a medicine for people could be found.
US patent 5,330,971 (GroPep Ltd; inventors Wells, King and Francis; priority June 1989, granted July 1994, now expired and assigned to Novozymes Biopharma DK) claims fusion proteins of the first 11 residues of methionyl porcine GH with IGF-I, IGF-II or analogues, including the MpGH(11)VN/R3 IGF-I construct. Francis et al. (J Mol Endocrinol 1992; Cooperative Research Centre for Tissue Growth and Repair and CSIRO Division of Human Nutrition) described E. coli expression of Long IGF-I, Long [Gly3]-IGF-I and Long [Arg3]-IGF-I, noting that the hydrophobic extension improved refolding yields.
The same Adelaide group (Ballard, Tomas, Read, Owens, Wallace and colleagues) then compared LR3-IGF-I with IGF-I and des(1–3)IGF-I in rats, guinea pigs, pigs and marmosets through the 1990s. No investigational new drug programme or human study of IGF-1 LR3 could be identified. The nearest clinical relative is 765IGF-MTX, a methotrexate conjugate of a different Arg3 IGF-I variant with an 18-residue histidine-tag leader, whose registered study in myelodysplastic syndrome (NCT03175978) was terminated for funding after enrolling two participants. That molecule is not IGF-1 LR3.
What the data say
All the data come from cells and animals. In cells grown in the lab, IGF-1 LR3 was several times stronger than natural IGF-1. But this was only true when binding proteins were there.
Female rats were treated for two weeks. In them, it was about six times stronger than natural IGF-1 at boosting weight gain. The same was true for helping the body hold on to protein. In pigs, it lowered blood sugar more strongly than natural IGF-1. The effect also lasted longer. This is a reminder that IGF-1 acts partly like insulin.
There are no registered human trials. There are no published human studies. There is no data on safe doses, side effects or long-term effects in people. Some people claim it lasts many hours in the human body. There is no published human proof of this. In rats, the body cleared it faster than natural IGF-1.
In vitro: in L6 myoblasts LR3-IGF-I was more potent than IGF-I at stimulating protein and DNA synthesis and inhibiting protein breakdown, with the order of potency tracking weak IGFBP binding (Francis 1992).
Animal data: over 14 days of administration to normal female rats, both IGF-I and LR3-IGF-I increased body weight, nitrogen retention and food conversion efficiency and kept the fractional weights of gut, spleen and thymus at those typical of younger animals; in the growth measurements LR3-IGF-I was about six-fold more potent (Ballard 1993). In pigs given 20 or 50 µg/kg bolus doses, the IGF variants were 2–3 times more potent than IGF-I for glucose lowering and suppressed glucose for longer, with cumulative hypoglycaemia over four hours about twice that of IGF-I at equipotent doses; LR3-IGF-I was the only analogue more potent than IGF-I at lowering plasma amino acids (Tomas 1997).
Human data: none. ClinicalTrials.gov returned no study of IGF-1 LR3, Long R3 IGF-I or LR3-IGF-I. The contrasting approved molecule, mecasermin, is labelled with warnings for severe hypoglycaemia, intracranial hypertension, tonsillar and adenoidal hypertrophy and malignant neoplasia; those are mecasermin data, not LR3 data.
Regulatory picture
Approval: the FDA has not approved any medicine with IGF-1 LR3 in it. As far as could be found, no other regulator has either. The approved IGF-1 drug is mecasermin (Increlex). It was approved in 2005 for children with severe primary IGF-1 deficiency (their bodies make too little IGF-1). Mecasermin is the same as natural IGF-1. IGF-1 LR3 is a different, longer molecule. The approval does not cover it.
Compounding (pharmacies mixing their own versions): IGF-1 LR3 is not on the FDA’s list of substances put forward for pharmacy compounding. So it is not in the banned “Category 2” group. It is not under review either. It is a protein. So if it were meant as a medicine, it would count as a biological product. The FDA says biological products cannot use the pharmacy compounding exemptions.
Enforcement: no FDA warning letter naming it was found.
Sport: the World Anti-Doping Agency bans IGF-1 and its look-alikes at all times.
Approval: none. IGF-1 LR3 is not a component of any FDA-approved drug and has no USP monograph. Increlex (mecasermin, initial US approval 2005) is indicated for growth failure in children aged 2 years and older with severe primary IGF-1 deficiency or GH gene deletion with neutralising GH antibodies, at labelled doses starting at 0.04–0.08 mg/kg twice daily subcutaneously, up to 0.12 mg/kg twice daily; its label states it is not a substitute for GH.
Compounding: FDA’s 503A nominations list (updated 2026-05-14) contains no entry for IGF-1 LR3 or any IGF-1 analogue in any category, and it is not on the 503A bulks list in 21 CFR 216.23. Under 21 CFR 600.3(h)(6), an amino-acid polymer longer than 40 residues is a protein, and a protein applicable to treating disease is a biological product; FDA’s 2018 guidance states that a biological product subject to licensure under section 351 of the PHS Act is not a drug for purposes of sections 503A and 503B and is not eligible for their exemptions. Because FDA has made no substance-specific statement, the compounding field is recorded as unknown.
Sport: WADA 2026 section S2.3 prohibits insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues.
