Journal September 25, 2026 6 min read

Common misconceptions about the IGF-1 axis

The IGF-1 axis is a research target with a formal name, a defined receptor family, and a literature full of animal-only and in vitro findings. This page separates what the evidence shows from what it does not.

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Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a 70-amino-acid peptide hormone with a molecular weight of approximately 7.6 kDa. It is the primary mediator of growth hormone (GH) action and circulates bound to IGF-binding proteins, chiefly IGFBP-3. The work described here centres on the GH/IGF-1 axis and its receptor family, including the growth hormone receptor (GHR) and the insulin-like growth factor 1 receptor (IGF-1R).

IGF-1 is not a single-tissue signal. It is produced in the liver under GH control and also locally in many tissues, where it acts in paracrine and autocrine modes. The axis is therefore studied across endocrinology, oncology, metabolism, and paediatrics, and findings from one context do not automatically transfer to another. The sections below summarise specific research studies and state plainly where the evidence is animal-only or in vitro.

Research Studies

Metformin and dapagliflozin 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) [1]. Eighty-four eligible male patients aged 30–60 years, with HbA1c 7.0%–10.0%, CAP ≥248 dB/m, and on stable metformin monotherapy for at least 8 weeks, are randomised 1:1 to continue metformin alone or to receive metformin plus dapagliflozin 10 mg/day for 12 weeks [1]. The primary endpoint is the change in serum IGF-1 from baseline to 3 months between groups; secondary endpoints include changes in hepatic steatosis and glycaemic parameters [1]. This is a registered trial protocol; results are not yet available in the evidence block.

Exercise as a disease-modifying therapy in colon cancer

The CHALLENGE trial, a phase III randomised study, tested a 3-year structured physical activity programme in patients with resected colon cancer [2]. The programme significantly improved disease-free survival (HR 0.72) and overall survival (HR 0.63) [2]. A review synthesising clinical, epidemiological, and translational evidence describes this as establishing exercise as a validated, disease-modifying intervention in this population [2]. The trial did not measure IGF-1 as its primary endpoint, and the review does not attribute the survival benefit to the IGF-1 axis specifically; the relevance here is that physical activity is a known modifier of GH/IGF-1 physiology, and the CHALLENGE result shows that a lifestyle intervention can change hard clinical outcomes in a cancer population.

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

A study investigated 7,344 serum samples from 2,508 healthy participants aged 3 months to 19 years, comparing anthropometric measurements and serum IGF-1 and IGFBP-3 concentrations between dietary groups using optimal 1:3 pair matching from age 10 [3]. Vegan children were shorter than vegetarians after adjustment for pubertal status (β = −0.59, p = 0.006) [3]. The abstract reports that IGF-1 and IGFBP-3 differed among dietary groups, though the full direction and magnitude of those differences are not given in the evidence block. This is observational data in children; it does not establish that any dietary pattern causes a change in the IGF-1 axis, only that associations were observed.

MAR002, a long-acting allosteric growth hormone receptor antagonist, in acromegaly models

Acromegaly is caused by GH hypersecretion from a pituitary adenoma, and pegvisomant is the only approved GH receptor antagonist, requiring daily subcutaneous injections [4]. MAR002 is a novel half-life-extended monoclonal antibody GH receptor antagonist identified by immunising transgenic mice with the extracellular domain of human and cynomolgus monkey GHR, then engineered with Fc modifications to limit effector function and extend serum half-life [4]. MAR002 was benchmarked against pegvisomant in biophysical assays, cellular signalling inhibition studies, and animal models [4]. This is preclinical development work; no human efficacy or safety data are reported in the evidence block.

AgRP and the GH/IGF-1 axis in children

Recent data support a GH–Agouti-related peptide (AgRP) axis, in which GH stimulates AgRP and AgRP may mediate some of GH's nutritional and metabolic effects [5]. A registered project aims to characterise plasma AgRP levels in children for the first time and to determine how they relate to GH and IGF-1 levels, age, body composition, and other endocrine parameters [5]. The project comprises a cross-sectional study measuring AgRP in 140 healthy children aged 5–17 and a prospective study [5]. This is a study protocol; no results are reported in the evidence block.

Precision medicine in paediatric growth disorders

A systematic scoping review of PubMed-indexed literature from 2000 to 2026 examined precision medicine in paediatric growth disorders, integrating clinical phenotype, genetics, IGF-1 biology, and artificial intelligence [6]. The review notes that recombinant human growth hormone 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 [6]. This supports the general point that IGF-1 axis biomarkers are not uniformly predictive across individuals, but the review is a synthesis and does not itself report a new trial.

Pharmacogenetic hypersensitivity to somatropin in a child with MC4R variant

A case report describes a child with severe growth hormone deficiency and an MC4R p.V166I variant who showed hypersensitivity to somatropin [7]. The melanocortin-4 receptor is a G protein-coupled receptor that regulates energy homeostasis, and pathogenic MC4R variants are the most common cause of monogenic obesity and are frequently associated with increased linear growth [7]. The mechanisms linking MC4R signalling to somatic growth are not fully established [7]. This is a single case; it does not establish a general rule about IGF-1 axis responsiveness.

Diabetes mellitus and cancer risk: epidemiology to molecular mechanisms

A review systematically analysed recent research on the relationship between diabetes mellitus and cancer risk, covering epidemiological and molecular mechanism studies [8]. Epidemiological data indicate an association between diabetes and cancer risk, and the review discusses molecular mechanisms that may underlie it [8]. The IGF-1 axis is one candidate mechanism in this literature, but the evidence block does not specify that the review isolates IGF-1 as the causal pathway. The association is not proof of causation.

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