IGF-1 side effects

What is known for IGF-1 LR3

ClinicalTrials.gov lists no registered human study of IGF-1 LR3, so no trial has measured its safety in people, and every frequency on this page comes from recombinant human IGF-1 (mecasermin and related forms).¹ German anti-doping scientists who analyzed a black-market vial found LR3 with an added purification tag, and noted that its effects in humans have not been described; they suggested it may be a by-product of lab studies rather than a product made for injection.¹⁸⁴

How closely LR3 would mirror IGF-1 in people is unknown. It binds IGF-binding proteins about 1,000 times more weakly, and rats eliminated it from the bloodstream far more quickly than IGF-1.¹⁹²⁰ Read the IGF-1 profile for how the two molecules differ.

Common effects in trials of recombinant IGF-1

The Increlex label pools 71 children with severe primary IGF-1 deficiency, treated for an average of 3.9 years (274 subject-years). No child left a study because of an adverse reaction.²¹

• Low blood sugar (hypoglycemia): 42% of the 71 children had it at least once, mostly mild or moderate.² In a separate long-term study of 76 children, it was the most common adverse event, reported by 49%, and it was also seen before treatment began.⁵
• Fat buildup at injection sites (lipohypertrophy): 32% in the 76-child study; the label also lists bruising.⁵²²
• Enlarged tonsils: 15% (11 of 71) in the first 1 to 2 years of treatment; enlarged tonsils or adenoids: 22% in the 76-child study.²³⁵ Reported complications include snoring, sleep apnea and long-lasting fluid in the middle ear.²⁴
• Other reactions in 5% or more of the 71 children: headache, dizziness, convulsions, vomiting, ear infections, fluid in the middle ear, ear pain, reduced hearing, abnormal eardrum tests, snoring, joint pain, limb pain, heart murmur and an enlarged thymus.²²²⁵
• Lab changes: mild rises in the enzymes AST and LDH in a significant share of patients, before and during treatment, which did not lead anyone to stop.²⁶
• Antibodies: anti-IGF-1 antibodies appeared in 14 of 23 children treated for 2 years.²⁷

Serious effects

• Severe hypoglycemia: 5 of 71 children needed someone else's help to treat it, and 4 had seizures or loss of consciousness.⁷
• Raised pressure inside the skull (intracranial hypertension), with swelling of the optic disc, vision changes, headache, nausea or vomiting: the label says these signs resolved after dosing was interrupted.²⁸ In the trials it occurred in 3 subjects, and in 2 of them it resolved without interrupting treatment.²⁹
• Severe allergic reactions: after marketing, cases suggesting anaphylaxis were estimated at 0.3%, with hives, swelling (angioedema) and trouble breathing; some patients were hospitalized.³⁰
• Bone problems during fast growth: slipped capital femoral epiphysis, where the top of the thigh bone slips at the growth plate and can lead to bone death, and worsening of existing scoliosis.³¹³²
• Tumors: malignant tumors of many types were reported in treated children after marketing, seen more often with doses above the recommended range or with IGF-1 levels pushed past the normal range for the child's age and sex. The label says it is unknown whether Increlex is related to them, and most were in children with conditions that already raise cancer risk.⁹¹⁰
• Skin and injection sites, after marketing: hair loss, abnormal hair texture, and injection-site redness, pain, bleeding, bruising, hardening, rash and swelling.³³

Effects at high doses in adults

Seven obese, insulin-resistant adults with type 2 diabetes received 120 or 160 micrograms/kg twice daily; every one developed side effects, and all stopped before the planned 8 weeks.³⁴³⁵ Reported effects were swelling, mainly of the face and hands, mild weight gain, occasional shortness of breath, jaw tenderness on both sides, joint and muscle pain, fatigue, a fast heart rate, flushing, low blood pressure on standing and burning at the injection site.³

A 2008 review of IGF-1 trials lists swelling, headache, joint pain, jaw pain and hypoglycemia as the commonest short-term side effects.³⁶ The same reviewers note that experience with injected IGF-1 is limited, and a 2009 review states that the effects of long-term IGF-1 misuse are unknown.³⁷³⁸

Cancer: what the evidence shows

Three kinds of evidence raise the question, and none shows cause and effect in people. Increlex is contraindicated in children with current or past cancer, and the label's tumor reports were more frequent at higher than recommended doses.¹¹¹⁰ In a 2-year study of daily injections at 0.25 to 10 mg/kg, mecasermin raised rates of adrenal tumors in rats, and doses above the maximum tolerated dose also caused skin and breast tumors.¹²

A large human data set looks at the body's own IGF-1, not injected IGF-1. Among 394,388 cancer-free adults in UK Biobank, followed for an average of 6.9 years, higher blood IGF-1 was linked to higher rates of thyroid cancer (hazard ratio 1.18 per 5 nmol/L), breast cancer (1.11), and colorectal and prostate cancer (1.08 each), and to lower rates of ovarian and liver cancer.³⁹⁴⁰¹⁴ The authors note that reverse causation cannot be ruled out.¹⁴

Warnings

• Benzyl alcohol: Increlex is preserved with benzyl alcohol, which can cause serious and fatal "gasping syndrome" in newborns and infants.⁴¹
• Pregnancy and older adults: there are no data on Increlex in pregnant women, and its safety and effectiveness have not been established in people 65 and older.⁴²⁴³
• Product quality: in a 2018 inspection, FDA investigators noted that a compounding pharmacy had documented 5 sterility failures since January 2016, including lots of IGF-1 made on October 30, 2017 and IGF-1 LR3 made on December 20, 2017. These were inspection observations, not final FDA findings.⁴⁴⁴⁵⁴⁶
• Dosing rules: the label's meal timing and activity limits for Increlex are set out on the IGF-1 dosage page.

Related pages

The IGF-1 profile covers what IGF-1 and LR3 are and the research behind them, and IGF-1 dosage lists the label schedule and study doses. Peptide safety basics covers the quality, sterility and storage checks that apply to any peptide vial.