Insulin-like growth factor 1 (IGF-1) is a small protein hormone made mainly in the liver in response to growth hormone (GH). It carries out much of GH’s growth-promoting effect and also has insulin-like effects on blood sugar. A recombinant version identical to human IGF-1, called mecasermin, is sold as Increlex.
Increlex is FDA-approved for one narrow use: growth failure in children aged 2 and older with severe primary IGF-1 deficiency (most often Laron syndrome, where the body cannot respond to GH) or with a GH gene deletion and neutralizing antibodies to GH. It is not approved for adults, for muscle building or for anti-aging. Its most common serious side effect is low blood sugar (hypoglycemia), and in controlled trials in adults it has not increased lean mass.
This page summarizes what the FDA label, clinical trials and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Peptide hormone; recombinant human IGF-1 (rhIGF-1) |
| Brand / approval | Increlex (mecasermin), BLA 021839, FDA-approved August 2005; EU-authorized August 2007 |
| Route | Subcutaneous injection only (label says never intravenous) |
| Strength | 40 mg/4 mL (10 mg/mL) multiple-dose vial |
| Labeled dose | 0.04–0.08 mg/kg twice daily, up to a maximum of 0.12 mg/kg twice daily |
| Half-life | Free IGF-1 ≈ 10–12 min (tracer study); Increlex terminal half-life 5.8 h after subcutaneous dosing in children |
| Key mechanism | Activates the type 1 IGF receptor, which is closely related to the insulin receptor |
| Most common serious risk | Hypoglycemia: reported at least once by 42% of children in the label’s trials |
| WADA status | Prohibited at all times (S2.3, growth factors) |
What it is
IGF-1 is a single chain of 70 amino acids held together by three internal disulfide bridges, with a molecular weight of 7649 Da. Rinderknecht and Humbel worked out its full sequence in 1978 and showed it closely resembles proinsulin, the precursor of insulin (Rinderknecht & Humbel, J Biol Chem 1978). That shared ancestry explains why IGF-1 can lower blood sugar.
In the body, GH binds its receptor in the liver and other tissues and triggers IGF-1 production. IGF-1 then acts on the type 1 IGF receptor in target tissues (Increlex label). The label lists these actions:
- Bone growth: IGF-1, together with GH, drives the cartilage cells in growth plates that lengthen bones until the plates fuse after puberty.
- Cell and organ growth: IGF-1 receptors are found on most cell types, and IGF-1 stimulates cell division.
- Glucose metabolism: IGF-1 suppresses glucose output by the liver, increases glucose uptake by tissues and inhibits insulin secretion.
Mecasermin has the same amino-acid sequence as natural human IGF-1. It is made in E. coli bacteria that carry the human IGF-1 gene.
In a study of two healthy adults, the body’s own IGF-1 production was estimated at about 10 mg per day (Guler et al., Acta Endocrinol 1989).
IGF-1 and related products
Several IGF-1-related products exist. This page covers native IGF-1 and mecasermin; the others have their own pages.
| Product | What it is | Approval status |
|---|---|---|
| Mecasermin (Increlex) | Recombinant IGF-1, identical to human IGF-1 | FDA-approved 2005; EU-authorized 2007 |
| Mecasermin rinfabate (iPlex) | A complex of recombinant IGF-1 with its main binding protein, IGFBP-3 | FDA-approved December 2005; now listed as discontinued |
| IGF-1 LR3 | Synthetic IGF-1 analogue with an N-terminal extension and one amino-acid change; binds IGF-binding proteins poorly | Not approved; a research chemical |
| IGF-1 DES | Synthetic truncated IGF-1 analogue | Not approved; a research chemical |
| MGF and PEG-MGF | Peptides based on a splice variant of the IGF-1 gene | Not approved; a research chemical |
Approval data come from Drugs@FDA. By 2009, mecasermin rinfabate was no longer available in the US or Europe for short stature, because of a legal requirement (Kemp, BioDrugs 2009). Anti-doping labs describe LR3 and DES as synthetic IGF-1 analogues (Thomas et al., Growth Horm IGF Res 2017) and MGF as a splice variant of IGF-1 (Esposito et al., Rapid Commun Mass Spectrom 2012).
Pharmacokinetics
Almost all IGF-1 in blood is bound to carrier proteins. According to the label, more than 80% circulates in a three-part complex with IGF binding protein 3 (IGFBP-3) and a protein called the acid-labile subunit. Binding largely determines how long IGF-1 lasts.
A tracer study in two healthy adults measured the half-life of each form (Guler et al., Acta Endocrinol 1989):
| Form of IGF-1 | Apparent half-life |
|---|---|
| Free (unbound) IGF-1 | 10–12 min |
| In the smaller (≈ 50 kDa) binding-protein complex | 20–30 min |
| In the large (≈ 200 kDa) complex with IGFBP-3 | 12–15 h |
The Increlex label reports these values for mecasermin injected under the skin:
| Parameter | Value |
|---|---|
| Bioavailability after subcutaneous injection | Close to 100% in healthy subjects; not determined in primary IGF-1 deficiency |
| Time to peak (0.12 mg/kg, n = 3 children with severe primary IGF-1 deficiency, ages 12–22) | 2 h |
| Peak concentration (same group) | 234 ng/mL |
| Terminal half-life (same group) | 5.8 h |
| Metabolism | Liver and kidney |
Children with severe primary IGF-1 deficiency have very low IGFBP-3. They therefore clear injected IGF-1 faster than healthy people. The label states that clearance is inversely proportional to IGFBP-3 levels: an estimated 0.04 L/h/kg at an IGFBP-3 level of 0.5 µg/mL, compared with 0.01 L/h/kg at 3 µg/mL, the median in people with normal IGF-1.
Approved medical use
United States
The Increlex label approves mecasermin for growth failure in children 2 years and older with either:
- severe primary IGF-1 deficiency, defined as height standard deviation score (SDS) of –3.0 or lower, basal IGF-1 SDS of –3.0 or lower, and normal or high GH; or
- a GH gene deletion with neutralizing antibodies to GH.
The label sets two limits on use. Increlex is not a substitute for GH in conditions where GH is approved. It is also not indicated for secondary IGF-1 deficiency, such as from GH deficiency, malnutrition, hypothyroidism or long-term corticosteroid use.
| Labeled dosing step | Dose |
|---|---|
| Starting dose | 0.04–0.08 mg/kg twice daily |
| Increase, if tolerated for at least 1 week | +0.04 mg/kg per dose |
| Maximum | 0.12 mg/kg twice daily |
The label requires each dose to be given within 20 minutes before or after a meal or snack. If the child cannot eat, the dose is skipped, and missed doses are never made up. Blood glucose is checked before meals at the start of treatment until a well-tolerated dose is found.
FDA first approved Increlex in August 2005 (Drugs@FDA). The current DailyMed label lists Eton Pharmaceuticals as manufacturer; an earlier label was issued by Ipsen.
European Union
The European Commission authorized Increlex in August 2007 for severe primary IGF-1 deficiency in children and adolescents (EMA). It was authorized under “exceptional circumstances,” which EMA uses when a disease is too rare for complete efficacy and safety data to be collected. It held orphan-medicine status from 2006 until 2017.
What the research shows
Severe primary IGF-1 deficiency
The label pools five studies (four open-label, one placebo-controlled) in 71 children. At baseline they averaged 6.7 years of age, had a height SDS of –6.7 and an IGF-1 level of 21.6 ng/mL. Of the 61 children treated for at least one year, 87% had Laron syndrome. Most received 0.06–0.12 mg/kg twice daily.
| Year of treatment | Children (n) | Height velocity, cm/yr | Height SDS |
|---|---|---|---|
| Before treatment | 58 | 2.8 | –6.7 |
| Year 1 | 58 | 8.0 | –5.9 |
| Year 2 | 48 | 5.8 | –5.6 |
| Year 3 | 38 | 5.5 | –5.4 |
| Year 4 | 23 | 4.7 | –5.5 |
| Year 6 | 20 | 4.8 | –5.4 |
| Year 8 | 13 | 4.3 | –5.2 |
The n column refers to height velocity. Growth was fastest in year 1 and then slowed. By years 7 and 8 the gain over pretreatment velocity was no longer statistically significant. Bone age advanced slightly faster than calendar age: 5.3 years compared with 4.9 years over the same period (n = 49).
The long-term US cohort followed 76 children for up to 12 years at 60–120 µg/kg twice daily. The first-year gain in growth rate depended on the dose (Chernausek et al., JCEM 2007). In the 21 children treated to adult or near-adult height (average 10 years of treatment):
- Average height gain was 13.4 cm more than expected without treatment.
- Height SDS improved by about +2 in total.
- Most still did not reach the normal adult height range (Backeljauw et al., Horm Res Paediatr 2013).
Effects on blood sugar
The first human study gave a single 100 µg/kg intravenous bolus of rhIGF-1 to eight healthy adults and compared it with insulin (Guler et al., NEJM 1987):
- Blood glucose bottomed out at 30 minutes, at 1.98 mmol/L (≈ 36 mg/dL) after IGF-1 and 1.78 mmol/L (≈ 32 mg/dL) after insulin.
- Mole for mole, IGF-1 was about 6% as potent as insulin at causing hypoglycemia.
- After the injection, about 80% of the IGF-1 in blood was free rather than bound. The authors linked the hypoglycemia to this surge of free IGF-1.
Because of these effects, rhIGF-1 was tested in diabetes. In 12 obese patients with type 2 diabetes, 100 µg/kg twice daily for 6 weeks gave these results (Moses et al., Diabetes 1996):
| Measure | Before | After treatment |
|---|---|---|
| HbA1c (average blood sugar marker) | 10.4% | 8.1% |
| Mean 24-h blood glucose | 14.7 mmol/L | 9.1 mmol/L |
| Insulin sensitivity index | Baseline | 3.4× higher |
| Serum IGF-1 | 206 µg/L | 849 µg/L |
Side effects were significant, however, and only 6 of the 12 patients completed all 6 weeks. In a separate study, all 7 patients given 120–160 µg/kg twice daily had to stop early because of side effects (Jabri et al., Diabetes 1994). The authors called high-dose rhIGF-1 an unacceptable treatment for these patients. IGF-1 has not been approved for diabetes.
Muscle and body composition in adults
IGF-1 is often described as an anabolic hormone, and short-term infusion studies support an effect on muscle protein. When rhIGF-1 was infused directly into the forearm artery of 19 adults for 6 hours, the forearm muscle shifted toward net protein gain at all three doses tested (Fryburg, Am J Physiol 1994). Muscle in the opposite arm, reached only through the general circulation, showed no change.
Controlled trials of injected IGF-1 have not shown gains in lean mass:
| Trial | Participants | Treatment | Lean mass result |
|---|---|---|---|
| Friedlander et al., JCEM 2001 | 16 healthy postmenopausal women, average age 71 | rhIGF-1 15 µg/kg twice daily or placebo, 1 year | No change in lean mass, fat mass, strength, bone density, mood or memory |
| Guha et al., JCEM 2015 | 56 recreational athletes (30 men, 26 women) | rhIGF-1/IGFBP-3 complex at 30 or 60 mg/day, or placebo, 28 days | No change in lean or fat mass |
In the 2001 trial, IGF-1 levels rose from about 66 to about 330 ng/mL. The study was stopped after 16 women because no outcomes were changing. In the athletes, maximal oxygen uptake (VO₂ max) rose by about 7% in the combined treated groups, a measure of aerobic capacity rather than muscle size.
Amyotrophic lateral sclerosis (ALS)
A phase 3 randomized, double-blind trial gave 330 patients with ALS either 0.05 mg/kg rhIGF-1 twice daily or placebo for 2 years (Sorenson et al., Neurology 2008). There was no difference in muscle strength, tracheostomy-free survival or functional decline. The authors concluded that IGF-1 does not benefit patients with ALS.
Preterm infants
IGF-1 levels fall sharply after very preterm birth, and IGF-1 (given intravenously as mecasermin rinfabate) has been tested to prevent retinopathy of prematurity, an eye disease of premature babies. A 2026 Cochrane review found only two trials with 140 infants (Trzaski et al., Cochrane 2026):
- Severe retinopathy needing treatment: RR 0.94 (95% CI 0.38–2.35).
- One or more serious adverse events: RR 1.18 (95% CI 0.94–1.47).
All evidence was rated very low certainty, and the reviewers could draw no conclusions about benefit or harm.
Side effects and risks
Hypoglycemia
This is the label’s first warning. Severe hypoglycemia has caused seizures. In 71 children treated for an average of 3.9 years (Increlex label):
- 30 children (42%) had hypoglycemia at least once, though 14 of them had a history of hypoglycemia before treatment.
- 5 had severe episodes needing help from another person.
- 4 had hypoglycemic seizures or loss of consciousness.
- Episodes were most frequent in the first month and in younger children.
The label advises avoiding high-risk activities such as driving or exercise for 2–3 hours after a dose, especially early in treatment. In the long-term cohort, hypoglycemia was reported by 49% of children (Chernausek et al., JCEM 2007).
Other labeled warnings
| Risk | What the label reports |
|---|---|
| Tonsil and adenoid enlargement | 15% of children in the first 1–2 years; 7 needed surgery, 3 of whom had obstructive sleep apnea |
| Intracranial hypertension (raised pressure around the brain) | 3 children; symptoms include headache, vision changes, nausea and vomiting |
| Slipped capital femoral epiphysis | The top of the thigh bone slips at the growth plate during rapid growth; can lead to bone death (osteonecrosis) |
| Scoliosis | Existing spinal curves may progress during rapid growth |
| Allergic reactions | Postmarketing anaphylaxis estimated at 0.3%; some patients needed hospitalization |
| Injection sites | Lipohypertrophy (fatty lumps) and bruising; lipohypertrophy affected 32% in the long-term cohort |
| Benzyl alcohol preservative | Linked to fatal “gasping syndrome” in newborns; use in infants not recommended |
The label also describes enlargement of the kidneys and spleen on ultrasound, thickening of the soft tissues of the face, and cardiac findings of unclear relation to the drug. It states that long-term overdosage may produce signs of acromegaly, the condition caused by GH excess.
Malignancy
Increlex is contraindicated in children with active or past cancer. There have been postmarketing reports of a variety of cancers in children treated with it. The label says it is unknown whether the drug caused them, but notes that tumors were seen more often in patients:
- with rare genetic conditions that already raise cancer risk;
- given higher than recommended doses, or doses that pushed IGF-1 above the normal range.
In a 2-year study in rats, mecasermin increased adrenal tumors at exposures below those in humans, and skin and breast tumors only at doses above the maximum tolerated dose.
Human observational data point in the same direction. A meta-analysis of 21 studies found that people with IGF-1 levels at the 75th percentile, compared with the 25th, had higher risk of prostate cancer (OR 1.49, 95% CI 1.14–1.95) and premenopausal breast cancer (OR 1.65, 95% CI 1.26–2.08) (Renehan et al., Lancet 2004). The associations were modest and varied by cancer site.
At the other extreme, Ecuadorians with GH receptor deficiency, who have very low IGF-1, were followed for 22 years. They had only one nonlethal cancer, compared with 17% in their relatives (Guevara-Aguirre et al., Sci Transl Med 2011). These are associations, not proof that raising IGF-1 causes cancer.
High doses in adults
In obese adults with type 2 diabetes given 120–160 µg/kg twice daily, every patient had side effects that forced treatment to stop (Jabri et al., Diabetes 1994):
- swelling, mainly of the face and hands;
- jaw tenderness, joint pain and muscle pain;
- fast heart rate, flushing and low blood pressure on standing;
- fatigue and occasional shortness of breath.
Who should not use it
The label lists these contraindications:
- known allergy to mecasermin or its ingredients;
- closed growth plates (the drug is only approved to promote growth);
- active cancer or a history of cancer.
Safety has not been established in children under 2 or adults 65 and over. The label also tells patients to report diabetes and use of insulin or other diabetes drugs, as their doses may need adjusting.
Legal status and use outside medicine
In the US, mecasermin is a prescription-only biologic approved solely for the pediatric indication above.
The WADA 2026 Prohibited List bans IGF-1 at all times under S2.3 (growth factors). The ban names “insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues” and mechano growth factors.
Anti-doping researchers report that IGF-1 products and analogues are advertised online and sold on the black market. They also note that IGF-1 is harder to detect than GH: as of 2013, no test for IGF-1 misuse was yet in place (Guha et al., Anal Bioanal Chem 2013). Labs have since published mass-spectrometry methods for synthetic analogues such as IGF-1 LR3 and IGF-1 DES (Thomas et al., Growth Horm IGF Res 2017). Products sold outside pharmacies are not regulated for identity, dose or sterility.
For the hormone upstream of IGF-1, see HGH. For the hormone it most resembles, see insulin.
Key takeaways
- A narrow approval. Mecasermin (Increlex) is approved only for growth failure in children with severe primary IGF-1 deficiency or GH gene deletion with GH antibodies, not for adults or performance.
- It acts like insulin. Hypoglycemia affected 42% of treated children, with seizures in some, which is why each dose must be given with a meal or snack.
- Short-lived when free. Unbound IGF-1 lasts about 10–12 minutes; injected mecasermin has a terminal half-life of about 6 hours in children.
- Real growth benefit in the right patients. Growth rate rose from 2.8 to 8.0 cm/yr in the first year, and treatment to adult height added about 13 cm, though most patients remained short.
- No muscle gain in adult trials. One year in older women and 28 days in athletes produced no change in lean mass.
- Cancer is a labeled concern. Tumors were reported more often at above-recommended doses, and high natural IGF-1 levels are modestly linked to some cancers.
Sources
- Eton Pharmaceuticals. Increlex (mecasermin) injection, prescribing information. DailyMed.
- Food and Drug Administration. Drugs@FDA: Increlex, BLA 021839; iPlex (mecasermin rinfabate), BLA 021884. FDA (Increlex); FDA (iPlex).
- European Medicines Agency. Increlex (mecasermin): EPAR. EMA.
- World Anti-Doping Agency. 2026 Prohibited List. WADA 2026 Prohibited List.
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