Journal September 19, 2026 6 min read

What markers track the IGF-1 axis?

A research-supply overview of the markers used to track the IGF-1 axis, including IGF-1, IGFBP-3, GH, and AgRP, with study findings from clinical trials and observational cohorts.

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The IGF-1 axis is tracked primarily through serum concentrations of insulin-like growth factor 1 (IGF-1, also known as somatomedin C) and its principal binding protein, IGFBP-3, together with growth hormone (GH) and, in some research contexts, the neuropeptide AgRP. IGF-1 is a 70-amino-acid peptide hormone with a molecular weight of approximately 7.6 kDa; it is encoded by the IGF1 gene and shares structural homology with proinsulin. IGFBP-3 is the major circulating carrier protein for IGF-1, forming a ternary complex with the acid-labile subunit and extending IGF-1's half-life in circulation. In research settings, these markers are quantified in serum or plasma using immunoassays, and their concentrations are interpreted relative to age, sex, and pubertal status.

The work centres on the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, a signalling cascade in which pituitary-derived GH stimulates hepatic IGF-1 production and release, and IGF-1 in turn feeds back to modulate GH secretion. This axis acts through the growth hormone receptor (GHR) and the insulin-like growth factor 1 receptor (IGF1R), both of which are receptor tyrosine kinases.

Research Studies

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

A 3-month, single-center, prospective, randomized, 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]. A total of 84 eligible male patients (aged 30–60 years, HbA1c 7.0%–10.0%, CAP ≥248 dB/m, on stable metformin monotherapy for ≥8 weeks) will be randomized 1:1 to either 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; secondary endpoints include changes in hepatic steatosis and other metabolic parameters [1]. This study is ongoing and has not yet reported results.

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

The phase III CHALLENGE trial examined a 3-year structured physical activity program in patients with resected colon cancer. The trial reported significant improvements in both disease-free survival (HR 0.72) and overall survival (HR 0.63) [2]. While the CHALLENGE trial did not directly measure IGF-1 axis markers, it provides randomized evidence that a lifestyle intervention can modify disease outcomes in this population, and it has been cited in reviews that discuss the IGF-1 axis as a potential mediator of exercise effects [2]. The findings are specific to patients with resected colon cancer and should not be extrapolated to other populations or to IGF-1 markers directly.

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 serum IGF-1 and IGFBP-3 concentrations between dietary groups using optimal 1:3 pair matching from the age of 10 [3]. Vegan children were shorter than vegetarians after adjustment for pubertal status (β = −0.59, p = 0.006), but the study also reported differences in IGF-1 and IGFBP-3 levels among dietary groups [3]. These findings are observational and describe associations in healthy children; they do not establish causation or indicate that dietary modification alters IGF-1 axis markers in adults.

Long-acting allosteric growth hormone receptor antagonist for acromegaly

MAR002 is a novel, half-life extended monoclonal antibody growth hormone receptor antagonist (GHRA) developed for acromegaly, a rare disease caused by GH hypersecretion from a pituitary adenoma [4]. MAR002 was identified by immunizing 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. It was benchmarked against pegvisomant, the only approved GHRA, in biophysical assays, cellular signaling inhibition studies, and animal models [4]. This research is preclinical; MAR002 has not been approved for human use, and its effects on IGF-1 axis markers in humans are not yet established.

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 has important effects on energy homeostasis; evidence suggests that GH stimulates AgRP and that AgRP may mediate some of GH's nutritional and metabolic effects [5]. A project aims to characterize, for the first time, plasma levels of AgRP in children and to 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 levels in 140 healthy children ages 5–17 and a prospective study [5]. This research is ongoing; no results are yet available.

Precision medicine in pediatric growth disorders: integrating IGF-1 biology

A systematic scoping review of PubMed-indexed literature (2000–2026) examined precision medicine approaches in pediatric growth disorders, integrating clinical phenotype, genetics, IGF-1 biology, and artificial intelligence [6]. The review notes 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 [6]. This reference supports the broader context that IGF-1 axis biomarkers are central to evaluating growth disorders, but it does not provide primary data on specific markers.

Pharmacogenetic hypersensitivity to somatropin and MC4R variant

A case report described a child with severe growth hormone deficiency and an MC4R p.V166I variant who exhibited hypersensitivity to somatropin [7]. 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 [7]. This report suggests that MC4R signaling may intersect with the GH/IGF-1 axis, but the findings are from a single case and do not establish a generalizable marker relationship.

Diabetes mellitus and cancer risk: epidemiological and molecular mechanisms

A review systematically analyzed recent research on the relationship between diabetes mellitus and cancer risk, encompassing epidemiological and molecular mechanism studies [8]. Epidemiological data indicate an association between diabetes and increased risk of certain cancers, and molecular mechanisms under investigation include hyperinsulinemia, hyperglycemia, and alterations in the IGF-1 axis [8]. This reference provides context for why IGF-1 axis markers are studied in metabolic disease, but it does not report original marker data.

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