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Background Despite their important clinical value, second generation antipsychotics (SGAs) are known to induce weight gain, insulin resistance, and dyslipidemia. However, the extent of these metabolic alterations differs among patients, and there is a current lack of knowledge about the factors that influence this inter-variability. Circulating levels of insulin-like growth factor binding protein (IGFBP)-2 below 220ng/mL have been proposed as a potential integrative biomarker negatively associated with features of the metabolic syndrome, including waist circumference and hypertriglyceridemia. Thus, we tested the hypothesis that the metabolic alterations developed upon the use of SGAs are impacted by circulating IGFBP-2 levels. Methods In order to assess metabolic risk factors in schizophrenic patients using SGAs on the basis of their plasma IGFBP-2 levels, a cross-sectional study was performed in 97 young Caucasian men newly diagnosed with schizophrenia and treated with olanzapine or risperidone for approximately 20 months. Plasma glucose, insulin and IGFBP-2 levels, anthropometric data, as well as lipid-lipoprotein profiles were determined at the end of the treatments. Results Body weight, waist circumference and fasting insulin levels were similar between patients on olanzapine or risperidone. Plasma IGFBP-2 levels were also not different between the two groups (173 ± 15 vs 199 ± 16 ng/mL, respectively). As expected, IGFBP-2 concentrations were negatively correlated with BMI, waist circumference, insulin sensitivity, and plasma triglyceride levels in the entire cohort. However, the proportion of schizophrenic patients with a hypertriglyceridemia and large waist circumference ranged from 43% for olanzapine and 12% for risperidone users with IGFBP-2 levels lower than 220 ng/mL, compared to 8% and 0%, respectively for patients with plasma IGFBP-2 above this threshold (p = 0.0178). Discussion Our findings suggest that circulating levels of IGFBP-2 may underlie the inter-variability on metabolic risk in schizophrenic patients using SGAs. Longitudinal studies are required to evaluate whether IGFBP-2 levels can predict the development of a hypertriglyceridemic waist phenotype in this population. [ABSTRACT FROM AUTHOR]