Preliminary evaluation of oxyntomodulin as a biomarker for metabolic risk stratification in adults with obesity

Oxyntomodulin (OXM), secreted by enteroendocrine L-cells, regulates energy and glucose homeostasis and is a dual agonist of glucagon-like peptide-1 (GLP-1) and glucagon receptors (GCGRs), with anorexigenic, insulinotropic, and energy expenditure-enhancing effects. While synthetic analogues of OXM are under investigation as potential anti-obesity therapies, the physiological role and clinical significance of endogenous OXM in human obesity remain incompletely elucidated. This study aimed to evaluate fasting OXM levels and assess their association with anthropometric and biochemical parameters in individuals with varying degrees of excess weight.

The cross-sectional study included overweight (O1, n = 88) and obese (O2, n = 134) individuals, as well as a healthy control group (CG, n = 39). Body composition was assessed using dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA). Biochemical and hormonal analyses encompassed glucose-insulin homeostasis and lipid profile, with a focus on fasting OXM concentration. Insulin resistance (IR) and β-cell function were evaluated using validated indices.

Fasting OXM levels were significantly elevated in the O2 compared to both the O1 and CG (p < 0.0001). OXM positively correlated with several anthropometric parameters, including visceral adipose tissue (VAT) mass and volume in O2. Logistic regression showed that higher OXM was significantly associated with the risk of obesity. Additionally, an increase in the risk of IR and related metabolic complications was observed with an increase in OXM levels, mainly in advanced stages of weight gain.

These findings provide preliminary evidence that OXM constitutes a potential biomarker of visceral adiposity and early metabolic dysregulation, serving as a measurable indicator of IR in obesity.