IGF-1 LR3 is not mecasermin. The human evidence does not transfer.

Why this note exists

Most compounds in this index are unapproved and unstudied together. IGF-1 LR3 is unusual because the confusion runs the other way: there is an approved IGF-1 medicine, with a label, a European authorisation and a patient registry behind it, and none of it is about the substance in the vial. LR3 was engineered to differ from native IGF-1; evidence for the approved medicine does not establish the safety or effectiveness of that analogue.

In the index generated on September 3, 2026, 55 of 104 vendors carried an IGF-1 LR3 listing — 65 listings, twenty-third of the 83 stocked compounds by vendor coverage, ahead of melanotan-1 and SS-31 and just behind cagrilintide.[22] Forty-one of the 65 are 1 mg vials and seven are 100 microgram vials; four are sold as "Receptor Grade," which is cell-culture language, not clinical language.[22] Not one of the 65 listings names mecasermin or Increlex.[22]

A note on what kind of evidence this is: every efficacy and safety figure attributed to the approved drug below comes from a study in people, with its design and participant count attached. Every figure attributed to IGF-1 LR3 itself comes from an animal or in-vitro study, and is labelled as such in the same sentence as the number. Those two bodies of evidence are about different molecules and are never pooled here. Where a dose appears, it appears as its source published it.

The approval

What is actually approved, for whom, and against what

The approved product is mecasermin, recombinant human IGF-1, marketed as Increlex. Drugs@FDA records BLA 021839 with an original approval date of August 30, 2005, and the application has since passed from Ipsen to Eton Pharmaceuticals, which closed the acquisition on December 20, 2024 and whose label version is the current one.[2][21][1]

The indication is narrow and it is pediatric: "the treatment of growth failure in pediatric patients 2 years of age and older with severe primary IGF-1 deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH."[1] The label defines severe primary IGF-1 deficiency by three simultaneous criteria — height standard deviation score at or below −3.0, basal IGF-1 standard deviation score at or below −3.0, and normal or elevated growth hormone — and states in its limitations of use that the drug "is not indicated for use in patients with secondary forms of IGF-1 deficiency."[1]

Two contraindications matter for how this compound is actually used. Increlex "should not be used for growth promotion in patients with closed epiphyses," and it is "contraindicated in pediatric patients with malignant neoplasia or a history of malignancy."[1] The first of those rules out the adult population the research market serves, on the approved molecule, in the approved indication. The second is a statement about IGF-1 signalling and cancer risk that the label makes on its own authority.

In Europe the picture is the same and the caveat is louder. The European Medicines Agency lists Increlex as authorised on 3 August 2007 for "the long-term treatment of growth failure in children and adolescents with severe primary insulin-like-growth-factor-1 deficiency," notes that it remains under additional monitoring, and records that it was authorised under exceptional circumstances because of the rarity of the condition — the regulatory category for a medicine whose sponsor could not be expected to assemble comprehensive data.[3] Its orphan designation lapsed in August 2017 at the end of the ten-year exclusivity period, which is an expiry, not a withdrawal.[3]

The dose, reported as its source published it: the label's recommended starting dose is "0.04 mg/kg to 0.08 mg/kg of body weight twice daily by subcutaneous injection," increasable to "the maximum dose of 0.12 mg/kg of body weight given twice daily," given within twenty minutes of a meal, with preprandial glucose monitoring at initiation.[1] That is a weight-based pediatric dose for a different molecule, and pepmg does not convert a per-kilogram figure into an absolute one.

The pivotal evidence

Seventy-one children, and the comparison group is the children themselves

An approval is not a measure of how much evidence there was. The label's clinical studies section describes "[f]ive clinical studies (four open-label and one double-blind, placebo-controlled) ... conducted in 71 pediatric subjects with severe Primary IGFD," pooled for a single global efficacy and safety analysis.[1] Fifty-three of the 61 subjects in the efficacy population had Laron syndrome; 92% were pre-pubertal at baseline; mean baseline height standard deviation score was −6.7.[1]

The efficacy analysis is the part worth reading closely. In the label's own description, "[t]he height velocities at a given year of treatment were compared by paired t-tests to the pre-treatment height velocities of the same subjects completing that treatment year."[1] That is a within-patient comparison against each child's own prior growth rate, not a comparison against a control arm. For a disorder in which untreated children grow at a known and very slow rate it is a defensible design, and it is also the reason the approval rests on a smaller evidentiary base than the word "approved" suggests.

Figures as tabulated in the current US prescribing information for Increlex.[1]

The most recent human data are registry data. A January 2026 report in the Journal of Clinical Endocrinology & Metabolism analysed the Global Increlex Growth Forum Database and found 102 patients who reached near-adult height, with a mean height standard deviation score gain of 0.9 from treatment start, rising to 1.4 in treatment-naive pre-pubertal patients.[11] Among patients with Laron syndrome, only 10.5% reached a near-adult height inside the normal range.[11] The registry is a manufacturer-sponsored observational cohort with no control group, two of its authors are employed by Ipsen, and the authors present it as real-world effectiveness rather than as trial evidence.[11][14]

The other molecule

It was published in 1992, and the paper calls it a reagent

IGF-1 LR3 has a birth certificate. In June 1992 a group at the CSIRO Division of Human Nutrition in Adelaide described an Escherichia coli expression system for a family of IGF-I fusion peptides, among them "[Met1]-pGH(1-11)-Val-Asn-[Arg3]-IGF-I," which the paper names Long [Arg3]-IGF-I.[5] The construct is native IGF-I with glutamate at position 3 swapped for arginine and a thirteen-residue N-terminal extension borrowed from porcine growth hormone — eleven residues of pGH plus valine and asparagine — bolted onto the front.[5][6]

The paper states the purpose in its second sentence: these analogues "have properties that make them very useful reagents in the investigation of IGF-I action."[5] They were built as laboratory tools, and the potency that later became a selling point is, in the paper's own account, an artefact of that design: Long [Arg3]-IGF-I outperformed native IGF-I in cell lines that secrete IGF-binding proteins, and was less potent than native IGF-I in chicken embryo fibroblasts, a line that secretes no detectable binding proteins.[5] The extra potency is escape from the binding proteins, not a better signal at the receptor — which is precisely the property a cell-culture supplement wants and precisely the property that makes systemic behaviour in an intact animal harder to predict, not easier.

The animal record

Organs get bigger. The animal does not.

There is a real preclinical literature on this molecule, and it is more consistent than the marketing is. Every study in this section is an animal study; none of them is evidence about a person.

A 1995 infusion study in the Journal of Endocrinology gave female guinea pigs long R3 IGF-I at 120 micrograms a day for seven days. The fractional weights of adrenals, gut, kidneys and spleen rose significantly, and the authors' summary of the whole-animal result is four words long: "overall growth was not stimulated."[7]

The same shape appears in sheep. A 2021 study infused LR3 IGF-1 into late-gestation fetal sheep for one week, eight animals against eight saline controls: heart, adrenal and spleen weights were higher, myoblast proliferation in skeletal muscle was higher, insulin was lower — and fetal weight was not statistically different between groups (3.260 kg versus 3.682 kg, P = 0.15), with umbilical amino acid uptake and fetal amino acid concentrations lower on the analogue.[8] A January 2025 follow-up from the same group tested it where it was supposed to help most, in growth-restricted fetal sheep, seven per group: "a 1-wk IGF-1 LR3 treatment did not improve growth in FGR fetuses," and circulating amino acids fell.[9]

The rat study is the only administered-dose record for this compound anywhere in pepmg's corpus, and it is a hydrogel implant in Lewis rats.[10]

The gap

Zero registered studies, and a review that says so in as many words

A ClinicalTrials.gov intervention search for IGF-1 LR3 on 6 September 2026 returns no studies at all; the same search for mecasermin returns 37.[15][16] A general keyword search on "LR3" returns 130 records, essentially all of them acupuncture trials using the liver-3 point, which is why the intervention field is the one that answers this question.[15]

The literature agrees. A narrative review published in Frontiers in Endocrinology on 18 June 2026, searching PubMed, Google Scholar and the Cochrane Library from January 1989 to January 2026, assigned every compound it covered to one of four evidence tiers. Its verdict: "CJC-1295 without DAC, PEG-MGF, and IGF-1 LR3 (tier D) have no peer-reviewed human studies and are supported only by preclinical extrapolation and grey-literature user narratives."[4] Later in the same paper the authors put it flatly: "Mechanistic plausibility for tier-D compounds does not constitute clinical evidence and should not be interpreted as such."[4] They also state their own limits — this is a narrative review, not a systematic one, with no pre-registered protocol and no formal risk-of-bias appraisal.[4]

Where controlled human evidence on IGF-1 as a class does exist, it reads soberly. A Cochrane review published on 15 April 2026 found only two randomised trials, 140 preterm infants in total, of IGF-1 for retinopathy of prematurity, judged every result to be of very low certainty because of small enrollment and substantial risk of bias, noted both trials were industry-funded, and concluded that the authors "are not able to draw conclusions about the effects of treatment with IGF-1 in preterm infants."[12] The drug in those trials was mecasermin rinfabate, given intravenously to newborns — a third molecule again, and a third route.[12] A November 2025 systematic review of mecasermin in Rett syndrome reached a similar place, describing inconsistent behavioural and autonomic outcomes and calling for "larger, rigorously designed trials."[13]

What is on the record about risk

The label's cancer language, and what it is and is not about

There is no safety literature on IGF-1 LR3 in humans, because there is no human literature on IGF-1 LR3 at all. What exists is the approved molecule's label, and it should be read as what it is — a statement about mecasermin, in children, most of whom have rare genetic conditions.

That label reports "postmarketing reports of malignant neoplasms in pediatric patients who have received treatment with INCRELEX," representing "a variety of different malignancies," and states plainly that "[i]t is unknown whether there is any relationship between INCRELEX therapy and new occurrence of neoplasia."[1] It then records two patterns: the cases occurred "mostly ... in patients with rare genetic conditions of short stature associated with an increased risk of cancer, or in patients with other cancer predisposing conditions," and "[t]he tumors were observed also more frequently in patients who received INCRELEX at higher than recommended doses, or at doses that produced serum IGF-1 levels above the normal reference ranges for age and sex."[1] The label also carries a hypoglycemia warning — "[s]evere hypoglycemia leading to hypoglycemic seizures has been observed" — which is why dosing is tied to meals and glucose monitoring.[1]

None of that is a finding about IGF-1 LR3, and this note does not present it as one. It is the closest thing to a regulator-reviewed safety record that exists anywhere in the IGF-1 family, and the 2026 review frames the cancer question the same careful way: a concern that is "theoretical but clinically relevant," resting on epidemiology linking higher circulating IGF-1 to several cancers rather than on any trial of an analogue.[4]

Anti-doping is the one place where the analogue is named by a rulebook. The 2026 World Anti-Doping Agency Prohibited List, effective 1 January 2026, lists under S2.3, growth factors and growth factor modulators, "Insulin-like growth factor-1 (IGF-1, mecasermin) and its analogues" — prohibited at all times, in and out of competition.[17][18]

Elsewhere the regulatory record is an absence. IGF-1 LR3 does not appear on FDA's list of bulk drug substances that may present significant safety risks, current as of 22 April 2026 — PEG-MGF, the compound the 2026 review places in the same tier D, does appear there, with FDA noting it "has not identified any human exposure data" on it.[19][4] Nor was IGF-1 LR3 among the substances FDA's Pharmacy Compounding Advisory Committee reviewed at its peptide session on 23–24 July 2026.[20] Not being evaluated is not a clean bill of health; it is the absence of an evaluation.

The market

A 1 mg vial, a per-kilogram label, and no name in common

The distance between what is approved and what is sold is not mainly a distance in dose here — it is a distance in identity. The approved article is native human IGF-1 in a preserved solution, dosed per kilogram of a child's body weight, twice daily, with glucose monitoring.[1] What vendors ship is an engineered analogue as a lyophilised powder, most often in a 1 mg vial, occasionally in 100 microgram vials or multi-vial packs, and four listings still carry the cell-culture grading term "Receptor Grade."[22]

Across 65 listings from 55 vendors, not one names mecasermin, Increlex, or the approval that the compound's reputation quietly borrows.[22] pepmg makes no claim about the contents of any vendor's vial.

Three things this note is not saying

First, it is not saying IGF-1 does nothing. It is one of the best-characterised anabolic signals in mammalian biology, an approved medicine for a real disease, and the pathway it acts through is textbook.[1][4] Mechanism is not the missing piece here.

Second, it is not saying IGF-1 LR3 is dangerous. It is saying something narrower and more uncomfortable: nobody has looked. There is no human trial, no registered study, no published case series, and therefore no safety record either way.[4][15] Absence of evidence about a product is the finding, not a verdict on it.

Third, it is not saying the approved drug's evidence is bad. Seventy-one children with an ultra-rare disorder is what an ultra-rare disorder allows, and both FDA and EMA said so in the way they granted the approval — one on a pooled within-patient analysis, the other under exceptional circumstances.[1][3]

What this note is saying is narrow and checkable: the FDA-approved IGF-1 product is a different molecule from the one in the vials, it is licensed for children and contraindicated once the growth plates close, the analogue in the vials was published in 1992 as a laboratory reagent, and the registry returns no study that has ever given it to a person.[1][5][15]

Questions people are asking