IGF-1 LR3 / DES

What are IGF-1 LR3 and DES(1-3)?

IGF-1 is a protein that mediates a large part of the effects of growth hormone in the body. In the blood it circulates largely bound to IGF binding proteins; these proteins regulate how much IGF-1 reaches the tissues and how quickly. Two laboratory-made derivatives are designed to partly bypass this regulation.

DES(1-3)IGF-1 is a truncated form of IGF-1 lacking its first three amino acids (glycine, proline, glutamate). According to the 1996 review, this protein has also been isolated from cow colostrum, human brain and pig uterus, and probably arises from cleavage of IGF-1 in the body. The absence of glutamate at position 3 markedly reduces binding to binding proteins; for this reason DES(1-3) is generally about 10 times more potent than IGF-1 in stimulating growth and proliferation in cell cultures. This advantage is partly retained when given to a living organism, and selective effects are seen especially in intestinal tissues. When the review was written, clinical uses had never been evaluated. ^[3]

IGF-1 LR3 (Long R3 IGF-1) is a derivative with arginine placed in position 3 in place of glutamate and an additional amino acid extension added at the start. According to the 2026 review, these changes markedly reduce binding to binding proteins; because the molecule binds to the same IGF-1 receptor, it is expected to start similar growth and cell proliferation signals. The review notes that the half-life of IGF-1 LR3 in humans is not documented and that no peer-reviewed human study exists; it places the substance on the lowest step of its own four-step evidence scale (D: no human studies). ^[9]

These two substances differ from the peptides that increase growth hormone secretion: they target not growth hormone but its mediator, the IGF-1 receptor, directly. Other peptides of the growth hormone axis are covered in a separate guide: Growth hormone secretagogues.

Licensed reference: mecasermin

What is mecasermin approved for?

Mecasermin is a recombinant protein produced in bacteria with the same amino acid sequence as human IGF-1 (70 amino acids). ^[1] It is not the same molecule as IGF-1 LR3 and DES(1-3); studies done with mecasermin cannot be transferred to these analogs.

• US (FDA): According to the prescribing information, mecasermin is indicated for the treatment of growth failure in children aged 2 years and older with severe primary IGF-1 deficiency or with growth hormone gene deletion who have developed neutralizing antibodies to growth hormone. Severe primary IGF-1 deficiency is defined by height SDS ≤ –3, basal IGF-1 SDS ≤ –3 and normal or elevated growth hormone. Mecasermin is not a substitute for growth hormone; it is not indicated in secondary forms of IGF-1 deficiency such as growth hormone deficiency, malnutrition or hypothyroidism. ^[1]
• EU (EMA): Increlex received an EU-wide license in August 2007 for the long-term treatment of children aged 2–18 years with severe primary IGF-1 deficiency. Because the disease is rare, the license was granted under “exceptional circumstances”; that is, it was not possible to obtain complete information about the drug. The drug was designated an orphan medicine on May 22, 2006; this status was removed in August 2017 when the 10-year market exclusivity ended. The indication application for children with growth hormone gene deletion and antibody development was withdrawn at the end of the evaluation; this use is approved in the US but not in the EU. ^[2]

The evidence rests on small studies. According to the EMA summary, the drug was examined in five studies involving a total of 76 children; only one compared with placebo, in eight patients. In pooled results, growth velocity rose from 2.8 cm per year before treatment to 8.0 cm in the first year and 5.8 cm in the second year, and stabilized at about 4.7 cm per year from the fourth year. ^[2] The FDA prescribing information also reports the same values (2.8 cm to 8.0 cm) in 58 children with pre-treatment data in a pooled analysis of five studies in 71 children, four open-label and one double-blind placebo-controlled. ^[1]

Warnings in the prescribing information

The FDA prescribing information lists the following serious risks: ^[1]

• Low blood sugar: In clinical studies, hypoglycemia occurred at least once in 30 of 71 children (42%); 5 children had severe hypoglycemia and 4 children had hypoglycemia-related seizures or loss of consciousness. Mecasermin has an insulin-like blood-sugar-lowering effect.
• Lymphoid tissue growth: Tonsillar enlargement was seen in 11 children (15%); 7 children underwent tonsil or adenoid surgery. Snoring, sleep apnea and fluid accumulation in the middle ear were reported.
• Malignant tumors: After marketing, various malignant tumors were reported in children who received mecasermin. The relationship to treatment is not known. Cases were mostly reported in patients with rare genetic short stature syndromes that create a predisposition to cancer or with other cancer predisposition conditions; tumors were also more frequent in those who received doses higher than recommended or doses that produced IGF-1 levels above normal for age and sex. Mecasermin is contraindicated in children with active or past malignancy.
• Others: Increased intracranial pressure (3 children), slipped capital femoral epiphysis, progression of scoliosis, allergic reactions and severe allergy (anaphylaxis).

In a 2-year rat study, mecasermin increased the frequency of tumors of the adrenal gland (pheochromocytoma); skin and breast tumors were seen only in groups where the tolerable dose was exceeded. ^[1] In the EMA summary, the most common side effects (more than 1 in 10 patients) are headache, hypoglycemia, vomiting, tissue thickening at the injection site and middle ear infection. ^[2]

What do animal studies show?

Published studies on LR3 and DES(1-3) are animal and cell experiments. The findings are very far from supporting “builds muscle, burns fat” claims.

White and colleagues recall that in their earlier work, LR3 given to normal lamb fetuses increased body weight but lowered insulin and insulin secretion; this is background information in the introduction, not a result of this new study. ^[6] For DES(1-3), the review states that selective anabolic effects in animals are most evident in intestinal tissues. ^[3]

These data cannot be transferred to humans: the species, route of administration (continuous infusion) and durations (days) differ from real-world use, and no study measured muscle strength or performance in healthy adults.

Has native IGF-1 been tried in athletes?

According to the 2026 review, there is no peer-reviewed human study with IGF-1 LR3. ^[9] For DES(1-3), the 1996 review states that clinical uses had never been evaluated at that time. ^[3] Native IGF-1, however, was tried in a randomized, double-blind, placebo-controlled study in the United Kingdom with 56 recreational athletes (30 men, 26 women); according to the authors, there was no published evidence until then on the effect of giving IGF-1 on sports performance. Participants received for 28 days placebo or a combination of recombinant human IGF-1 with its binding protein IGFBP-3 at two different doses. ^[7]

• Body composition: Fat mass and lean mass did not change significantly in either women or men.
• Aerobic capacity: When the two active groups and both sexes were pooled, maximal oxygen consumption (VO2max) rose by about 7% on average (P = 0.001); no significant change was seen in the placebo group.

These results rely on comparing each participant with their own earlier value; the study is small and short. ^[7] More importantly, the substance used is native IGF-1 given together with its binding protein. LR3 and DES, which are designed not to bind to binding proteins, are expected to behave differently in the body; this study provides no information about them.

What are the risks and unknowns?

There are no human safety data for LR3 and DES(1-3). Risk assessment can be made indirectly from three sources:

1. Licensed related drug: The mecasermin prescribing information lists severe hypoglycemia, tonsillar enlargement, increased intracranial pressure and reports of malignant tumors. ^[1]
2. Animal data: Analogs lowered blood sugar more strongly and for longer than native IGF-1; researchers linked this to weak binding to binding proteins. ^[4]
3. 2026 review: It emphasizes that hypoglycemia is theoretically possible with IGF-1 analogs and that there is a biologically plausible but unproven concern about cell proliferation (cancer) due to prolonged IGF-1 receptor stimulation. The review also states that the content, dose and co-use practices of these products are uncertain in the unsupervised supply chain. ^[9]

Sterility and infection risks of unlicensed products used by injection are covered in a separate guide: Peptide side effects

What was found in black-market products?

In 2010, doping researchers found, in an injection vial obtained from the black market, an LR3 derivative with a histidine tag added to the C-terminus. Such tags are added to make protein purification easier in the laboratory; when added to the N-terminus, they are later removed with special enzymes. According to the authors, the effects of this molecule in humans are not defined, and the product may be a by-product of biochemistry work rather than being made for injection. ^[8] This is a single case report; however, it shows that there is no guarantee that a vial labeled “for research purposes” will contain exactly the declared molecule. The meaning of this label: What does research peptide mean?

FDA, EMA, WADA and Türkiye: what is the legal status?

US and EU

The IGF-1 drug licensed by the FDA and EMA is mecasermin (Increlex); IGF-1 LR3 and DES(1-3) are not covered by these licenses. ^{[1] [2]} In the FDA list of bulk substances nominated for use in compounding by pharmacies (503A, May 14, 2026 update), IGF-1 LR3 and DES(1-3)IGF-1 do not appear in any of category 1 (under evaluation), category 2 (significant safety risk) or category 3 (nominated without adequate support). ^[11] In the same document, mechano growth factor (MGF) from the IGF-1 family appears in category 3. ^[11] IGF-1 LR3 and DES(1-3) also do not appear on the FDA category 2 page dated April 22, 2026; from the IGF-1 family, this page includes only PEGylated mechano growth factor (PEG-MGF), in the table of substances withdrawn by nominators, with the note that no human exposure data exist and that it may carry a risk of immune response. ^[15] These lists are not a drug approval.

Sport (WADA)

In the WADA list valid from January 1, 2026, the S2.3 heading “growth factors and growth factor modulators” names insulin-like growth factor 1 (IGF-1, mecasermin) and its analogs; mechano growth factors (MGF) are also included under the same heading. Substances in class S2 are prohibited at all times, in and out of competition, and none of the substances in this class is a “specified substance”. ^[10]

Türkiye

The TİTCK (Turkish Medicines and Medical Devices Agency) Licensed Human Medicinal Products List dated October 16, 2026 contains no product with IGF-1 LR3, DES(1-3)IGF-1 or mecasermin as an active substance. ^[12] Article 19 of Law No. 1262 punishes those who manufacture unlicensed preparations and those who knowingly sell, offer for sale or have sold such preparations with imprisonment from one to five years; if the preparation is found to be made from impure substances, the penalty is increased by one third. The same penalty is prescribed for those who sell, market or advertise a product that is not a preparation with the claim that it diagnoses or treats diseases. Importing preparations made abroad without a license for commercial purposes counts as smuggling. ^[13] Under Article 24 of Law No. 6197, medicines cannot be sold on the internet or in any other electronic medium. ^[14]

General legal framework of peptides: Are peptides legal?

Evidence table: claim, population and limits

Limits of this guide

This page summarizes published studies and official agency documents on IGF-1 LR3, DES(1-3)IGF-1 and the licensed related drug mecasermin. It gives no dose, cycle, preparation, administration technique or product-sourcing information; applications in animal studies cannot be translated to humans. IGF-1 deficiency is a rare diagnosis that must be confirmed with laboratory tests and monitored by a pediatric endocrinology specialist.