What it is
IGF-1 (insulin-like growth factor 1) is a natural hormone, made mostly in the liver when growth hormone rises, that tells cells to grow and divide. In the blood, most IGF-1 is held by carrier proteins called binding proteins, which control how much is free to act.
IGF-1 LR3 is an engineered version. One building block near the start is swapped (an arginine in place of a glutamate), and 13 extra building blocks borrowed from pig growth hormone are added to the front. Together these changes make it largely ignore the binding proteins.
It is made by bacteria and is sold mainly as an ingredient that helps cells grow in laboratories and industrial bioreactors. It is not an approved medicine, and it is not mecasermin, the approved drug that is identical to 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 out of growth-factor research in Adelaide, Australia, in the late 1980s and early 1990s, involving the national science agency CSIRO, a government-backed research centre on tissue growth and repair, and a local company, GroPep. The researchers suspected that binding proteins in the blood were blunting the effect of IGF-1 given as a treatment, and built versions designed to escape them. A short piece of pig growth hormone at the front also helped bacteria fold the protein correctly.
GroPep patented the design and sold the long Arg3 version as an ingredient for growing cells, and later became part of Novozymes. No effort to develop IGF-1 LR3 as 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 data come from cells and animals. In cell cultures IGF-1 LR3 is several times stronger than natural IGF-1, but only when binding proteins are present. In female rats treated for two weeks, it was about six times more potent than natural IGF-1 at increasing weight gain and protein retention. In pigs it lowered blood sugar more strongly and for longer than natural IGF-1, a reminder that IGF-1 acts partly like insulin.
There are no registered human trials, no published human studies, and no data on safe doses, side effects or long-term effects in people. Claims that it lasts for many hours in the human body have no published human basis; in rats it was cleared faster than 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: no medicine containing IGF-1 LR3 has been approved by the FDA or, as far as could be found, any other regulator. The approved IGF-1 drug is mecasermin (Increlex), approved in 2005 for children with severe primary IGF-1 deficiency. Mecasermin is identical to natural IGF-1; IGF-1 LR3 is a different, longer molecule, and the approval does not cover it.
Compounding: IGF-1 LR3 does not appear anywhere on the FDA’s list of substances nominated for pharmacy compounding, so it is neither in the prohibited “Category 2” nor under review. Being a protein, it would also count as a biological product if intended as a medicine, and the FDA says biological products are not eligible for the pharmacy compounding exemptions.
Enforcement: no FDA warning letter naming it was found. Sport: the World Anti-Doping Agency prohibits IGF-1 and its analogues 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.
