Journal September 19, 2026 4 min read

How does the IGF-1 axis work?

The IGF-1 axis is a hormone–receptor system that links growth hormone signalling to cell growth, metabolism and tissue maintenance. This page outlines its components and summarises research findings from clinical, animal

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The IGF-1 axis is the endocrine and paracrine system centred on insulin-like growth factor 1 (IGF-1), a 70-amino-acid single-chain polypeptide hormone. IGF-1 is produced mainly in the liver under growth hormone (GH) stimulation, and it circulates bound to IGF-binding proteins (IGFBPs), chiefly IGFBP-3. The axis also includes the GH receptor (GHR), the IGF-1 receptor (IGF-1R), and the binding proteins that regulate IGF-1 availability. In research settings, serum IGF-1 and IGFBP-3 are measured as biomarkers of GH/IGF-1 axis activity.

The pathway centres on GH binding to the GHR, a cytokine receptor family member, which triggers JAK-STAT signalling and IGF-1 transcription; IGF-1 then acts through the IGF-1R, a receptor tyrosine kinase, to influence cell proliferation, differentiation and metabolism.

Research Studies

Metformin and dapagliflozin effects on serum IGF-1 in male T2DM with MASLD

A 3-month, single-centre, prospective, randomised, parallel-controlled, open-label trial is investigating the effects of metformin combined with dapagliflozin on serum IGF-1 levels in male patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD). Eighty-four eligible male patients (aged 30–60 years, HbA1c 7.0%–10.0%, CAP ≥248 dB/m, on stable metformin monotherapy for ≥8 weeks) are randomised 1:1 to continue metformin alone or receive metformin plus dapagliflozin 10 mg/day for 12 weeks. The primary endpoint is the change in serum IGF-1 from baseline to 3 months between groups [1].

Exercise as a disease-modifying therapy in colon cancer: the CHALLENGE trial

In the phase III CHALLENGE trial, a 3-year structured physical activity programme significantly improved both disease-free survival (HR 0.72) and overall survival (HR 0.63) in patients with resected colon cancer. The trial addressed a long-standing causality gap between observational associations of physical activity with improved colon cancer survival and randomised evidence [2].

Growth parameters and IGF-1 axis biomarkers in omnivorous, vegetarian and vegan children

A study of 7,344 serum samples from 2,508 healthy participants aged 3 months to 19 years compared anthropometric measurements and IGF-1 and IGFBP-3 serum concentrations between dietary groups using optimal 1:3 pair matching from age 10. Vegan children were shorter than vegetarians after adjustment for pubertal status (β = −0.59, p = 0.006) [3].

Long-acting allosteric growth hormone receptor antagonist for acromegaly

Acromegaly is a rare disease caused by GH hypersecretion from a pituitary adenoma. Pegvisomant is the only approved GH receptor antagonist (GHRA) and is administered via daily subcutaneous injections. MAR002, a novel half-life-extended monoclonal antibody GHRA, was identified by immunising transgenic mice with the extracellular domain of human and cynomolgus monkey GHR and engineered with Fc modifications to limit effector function and extend serum half-life. MAR002 was benchmarked against pegvisomant in biophysical assays and cellular signalling inhibition studies [4].

AgRP and the GH/IGF-1 axis in children

Recent data support the existence of a GH–Agouti-related peptide (AgRP) axis. AgRP is a neuropeptide that promotes food intake and affects energy homeostasis; evidence suggests GH stimulates AgRP and that AgRP may mediate some of GH's nutritional and metabolic effects. A project aims to characterise plasma AgRP levels in children and determine how these relate to GH and IGF-1 levels, age, body composition, and other endocrine parameters. The project includes a cross-sectional study measuring AgRP in 140 healthy children aged 5–17 and a prospective study [5].

Precision medicine in paediatric growth disorders

A systematic scoping review of PubMed-indexed literature (2000–2026) reports that recombinant human growth hormone (rhGH) has been used for four decades under a largely population-based dosing paradigm, yet growth response varies substantially among children with apparently similar auxological phenotypes. Advances in genomics and GH–IGF-1 axis biomarkers are discussed [6].

Pharmacogenetic hypersensitivity to somatropin in a child with severe growth hormone deficiency and MC4R p.V166I variant

The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor that regulates energy homeostasis. Pathogenic MC4R variants are the most common cause of monogenic obesity and are frequently associated with increased linear growth. A case report describes a child with severe growth hormone deficiency and an MC4R p.V166I variant who showed hypersensitivity to somatropin [7].

Diabetes mellitus and cancer risk: epidemiology to molecular mechanisms

A review systematically analyses recent research on the relationship between diabetes mellitus and cancer risk, covering epidemiological and molecular mechanism studies. Epidemiological data indicate an association between diabetes and cancer risk [8].

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