Mecasermin
IGF-1 as an actual medicine, for children who cannot make it, with the side effect that implies
Mecasermin is recombinant human IGF-1, approved in 2005 for children with severe primary IGF-1 deficiency. Its label is explicit that it does not replace growth hormone, and its characteristic risk is low blood sugar, because IGF-1 acts partly like insulin.
What is it?
Growth hormone works largely by raising IGF-1. Children who cannot make IGF-1 despite normal or high growth hormone, or who have developed antibodies to growth hormone, do not grow, and giving them growth hormone does not help. Mecasermin supplies the missing hormone directly.
The label sets the boundary clearly: for growth failure in children two years and older with severe primary IGF-1 deficiency or growth hormone gene deletion with neutralising antibodies, and not a substitute for growth hormone in its own indications. Dosing starts at 0.04 to 0.08 mg/kg twice daily under the skin and, if tolerated for a week, rises by 0.04 mg/kg per dose to a maximum of 0.12 mg/kg twice daily. Because it acts like insulin, each dose must be given within about 20 minutes of a meal or snack, and a dose is skipped if the child cannot eat. Injection sites are rotated to avoid fatty lumps.
The long-term data that supported approval came from children with severe IGF-1 deficiency due to growth hormone insensitivity. Height velocity rose from an average 2.8 cm a year before treatment to 8.0 cm a year in the first year, depending on dose, and stayed above baseline for up to eight years. Hypoglycaemia was reported by 49% of children, injection-site fat overgrowth by 32% and enlarged tonsils or adenoids by 22%, though these rarely forced treatment to stop.
Registry data now cover adult height. In 102 patients of the Global IGFD Registry who reached near-adult height, starting at a mean age of 11.8 and treated for a median of 3.9 years, height rose by a mean 0.9 standard deviations, and by 1.4 in children not yet in puberty, almost half of whom reached the normal range. Children with Laron syndrome gained height too, but only 10.5% reached the normal range. In an earlier registry analysis, 56% of prepubertal children without Laron syndrome responded, and younger age at the start predicted a better response.
Hypoglycaemia is the risk that follows from the biology, and it has been quantified in a registry: 0.11 hypoglycaemia events per patient per treatment year, of which 0.01 were serious. Children who had had hypoglycaemia before, or who had Laron syndrome, were more likely to have it on treatment. The label's other warnings include allergic reactions including anaphylaxis, raised pressure inside the skull, enlargement of tonsils and adenoids, slipped capital femoral epiphysis, worsening scoliosis, malignant neoplasia, and the risk of the benzyl alcohol preservative in infants.
Related products and other diseases have been tested outside the label. A combination of IGF-1 with its binding protein IGFBP-3, the pairing sold in the US as mecasermin rinfabate (iPlex, now discontinued), given to 121 preterm infants, did not reduce retinopathy of prematurity but was associated with fewer cases of severe bronchopulmonary dysplasia; fatal serious adverse events occurred in 19.7% of treated infants and 11.7% of controls. In amyotrophic lateral sclerosis, a Cochrane review of two placebo-controlled trials found a smaller difference in disability progression in the European trial (124 on IGF-1 against 59 on placebo) than in the North American one, and concluded it may be modestly effective but the evidence was insufficient for a definitive assessment.
Rett syndrome, a genetic neurodevelopmental disorder in girls, is where mecasermin has been tried most. In a 2014 phase 1 study, 12 girls completed four weeks of rising doses up to 120 µg/kg twice daily and 10 completed a 20-week extension, with no hypoglycaemia or serious adverse events; IGF-1 rose in the cerebrospinal fluid, apnoea improved and some anxiety and mood measures got better. A 2016 comparison of 10 treated girls with 10 untreated matched patients found better clinician and observer severity scores with treatment, and a 2025 systematic review concluded that it may help social engagement and cognition but that results elsewhere were inconsistent and larger trials are needed.
Mechanism of Action
Mecasermin is recombinant human IGF-1, supplying the hormone that growth hormone normally induces.
Direct IGF-1 replacement
Bypasses growth hormone insensitivity, which is why it works where growth hormone does not.
Insulin-like effect
IGF-1 lowers blood sugar, hence the meal rule and the hypoglycaemia warning (label).
Binding proteins
In blood more than 80% of IGF-1 is bound with IGFBP-3, which is greatly reduced in severe primary IGF-1 deficiency (label).
Published Research
The studies behind mecasermin, read from their PubMed abstracts: long-term growth, registry data on adult height and hypoglycaemia, and uses outside the label.
Long-term treatment in severe IGF-1 deficiency
Height velocity rose from 2.8 to 8.0 cm/yr in the first year and stayed above baseline for up to 8 years; hypoglycaemia was reported by 49%, lipohypertrophy by 32% and tonsillar or adenoidal hypertrophy by 22%.
Adult height, in the real world
In 102 registry patients who reached near-adult height, mean height SDS gain was 0.9 (1.4 in prepubertal starters, almost half reaching the normal range); only 10.5% with Laron syndrome reached the normal range.
How often blood sugar drops
Among 306 registry patients, there were 0.11 hypoglycaemia adverse events per patient per treatment year (0.01 serious); prior hypoglycaemia and Laron syndrome predicted them.
With and without Laron syndrome
In prepubertal children with severe primary IGF-1 deficiency, 56% without Laron syndrome responded, younger age predicting response; 65.3% had adverse events, most often hypoglycaemia.
A different formulation, in preterm infants
In 121 preterm infants, rhIGF-1/rhIGFBP-3 did not reduce retinopathy of prematurity but severe bronchopulmonary dysplasia was 21.3% against 44.9%; fatal serious adverse events 19.7% against 11.7%.
Tested in Rett syndrome
A systematic review found IGF-1 may help social engagement and cognition in Rett syndrome, with inconsistent autonomic and behavioural results, and called for larger trials.
Rett syndrome, phase 1
12 girls completed a 4-week ascending-dose phase (to 120 µg/kg twice daily) and 10 a 20-week extension without hypoglycaemia or serious adverse events; CSF IGF-1 rose, apnoea improved and some anxiety and mood measures improved.
Rett syndrome: 10 treated against 10 untreated
Clinician-rated (ISS, P = 0.0106) and observer-rated (RSS, P = 0.0274) severity improved more in treated girls than in matched untreated patients.
ALS: Cochrane review
Two placebo-controlled trials of rhIGF-I in ALS showed smaller benefit on disease progression in the European trial than the North American one; the review judged it possibly modestly effective, with evidence insufficient for a definitive assessment.
Dosing Data
Increlex is injected under the skin twice daily with meals, at a weight-based dose.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the trials above and the Increlex prescribing information (DailyMed set d5b2b0e1, version 5, effective May 18, 2026).
Contraindications & Cautions
From the label.
Legal Status
An approved paediatric medicine.
Frequently Asked Questions
?What is mecasermin?
Recombinant human IGF-1, given to children who cannot make their own despite normal growth hormone.
?Why not just give growth hormone?
Growth hormone works by raising IGF-1. In these children that step fails or antibodies block it, so the label states mecasermin is not a substitute for growth hormone in growth hormone's own indications.
?What is the main risk?
Low blood sugar, because IGF-1 has insulin-like activity. Registry data put it at 0.11 events per patient per treatment year, 0.01 of them serious.
?Does it improve adult height?
Recent registry data on near-adult height found improvement, even where treatment started relatively late.
?What dose is used?
0.04 to 0.08 mg/kg twice daily to start, rising by 0.04 mg/kg per dose to a maximum of 0.12 mg/kg twice daily, always with a meal or snack (label).
?How much faster do children grow?
In the long-term study, height velocity rose from 2.8 to 8.0 cm a year in the first year and stayed above baseline for up to eight years.
?Is it used for anything else?
It has been studied in Rett syndrome (small studies, some improvements in breathing and mood) and ALS (possibly modest benefit, evidence insufficient), and a related IGF-1 combination in preterm infants; none is an approved use.
References
- [fda-pi] Increlex (mecasermin) prescribing information, sections 1, 2 and 12.3 (DailyMed SPL version 5, effective May 18, 2026; read October 1, 2026).
- [pubmed] Chernausek SD, et al. "Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity." J Clin Endocrinol Metab, 2007;92(3):902-10. PMID: 17192294.
- [pubmed] Ramon-Krauel M, et al. "Near-Adult Height Outcomes in Patients Treated With rhIGF-1 for Severe Growth Failure: Real-World IGFD Registry Data." J Clin Endocrinol Metab, 2026;111(2):e500-e511. PMID: 40626687.
- [pubmed] Bang P, et al. "Frequency and Predictive Factors of Hypoglycemia in Patients Treated With rhIGF-1: Data From the Eu-IGFD Registry." J Clin Endocrinol Metab, 2023;109(1):46-56. PMID: 37579214.
- [pubmed] Bang P, et al. "Effectiveness and safety of rhIGF1 therapy in patients with or without Laron syndrome." Eur J Endocrinol, 2021;184(2):267-276. PMID: 33434161.
- [pubmed] Ley D, et al. "rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial." J Pediatr, 2019;206:56-65.e8. PMID: 30471715.
- [pubmed] Ribeiro FCP, et al. "Mecasermin for the treatment of Rett Syndrome: a systematic review." Neurogenetics, 2025;26(1):78. PMID: 41174329.
- [pubmed] Khwaja OS, et al. "Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome." Proc Natl Acad Sci U S A, 2014;111(12):4596-601. PMID: 24623853.
- [pubmed] Pini G, et al. "Illness Severity, Social and Cognitive Ability, and EEG Analysis of Ten Patients with Rett Syndrome Treated with Mecasermin (Recombinant Human IGF-1)." Autism Res Treat, 2016;2016:5073078. PMID: 26925263.
- [pubmed] Mitchell JD, et al. "Recombinant human insulin-like growth factor I (rhIGF-I) for amyotrophic lateral sclerosis/motor neuron disease." Cochrane Database Syst Rev, 2002:CD002064. PMID: 12137643.
- [pubmed] Backeljauw PF, et al. "Therapy for 6 years with recombinant human insulin-like growth factor-I in children with severe primary IGF-I deficiency." J Clin Endocrinol Metab.
Sources & Citations
Studies were read from their PubMed records (October 6, 2026); the label and Drugs@FDA are listed below with their read dates.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.