Insulin secretion and insulin sensitivity indexes are related by hyperbolic functions, allowing the calculation of the disposition index (DI) as the product of the acute insulin response (AIR) and the insulin sensitivity index (Si) from intravenous glucose tolerance test (IVGTT). Our objective was to develop an oral-DI based on the oral glucose tolerance test (OGTT) and to assess its association with glucose tolerance status. This research is structured in three studies. Study 1: OGTT were performed in 833 non-diabetic Chilean women (18-60 years) without family history of diabetes mellitus. Study 2: an independent group of n = 57 non-diabetic (18-46 years) without family history of diabetes mellitus carried out an OGTT and an abbreviated IVGTT. Study 3: a sample of 1674 Chilean adults (18-60 years) with different glycaemic status performed an OGTT. An adequate statistical fit for a rectangular hyperbola was found between the area under the curve of insulin-to-glucose ratio (AUCI/G-R) and the Matsuda ISI-COMP index (study 1). The oral-DI derived as AUCI/G-R × ISI-COMP was previously termed insulin-secretion-sensitivity index-2 (ISSI-2). ISSI-2 significantly correlated with DI from IVGTT (rho = 0.34; p = 0.009) (study 2). ISSI-2 shows important differences across groups of subjects with different glycaemic status (study 3). We have confirmed that ISSI-2 replicates the mathematical properties of DI, showing significant correlations with DI from the abbreviated MM-IVGTT. These results indicate that ISSI-2 constitutes a surrogate measure of insulin secretion relative to insulin sensitivity and emphasizes the pivotal role of impaired insulin secretion in the development of glucose homeostasis dysregulation.