We have developed a new model to describe endogenous glucose kinetics during a labeled (hot) intravenous glucose tolerance test (IVGTT) in order to derive a time profile of endogenous glucose production (EGP). We reanalyzed data from a previously published study [P. Vicini et al. Am. J. Physiol. 276 (Endocrinol. Metab. 39): E285-E294, 1999], in which insulin modified [6,6-²H₂]glucose labeled IVGTTs (0.33 g kg^-1 of glucose) were performed in 10 normal subjects. In addition, a second tracer ([U-¹³C]glucose) was infused in a variable rate in order to clamp the endogenous glucose tracer-to-tracee ratio (TTR). Our new model describing endogenous glucose kinetics was incorporated into the two compartment hot minimal model structure. The model gave estimates of glucose effectiveness (S_G^2* = 1.54±0.31 ml^.kg^-1.min^-1) [mean±SE], insulin sensitivity (S_I^2* = 37.74±5.23 10⁴ dl^.kg^-1.min^-1.µU^-1.ml) as well as a new parameter describing the sensitivity of EGP to the inhibitory effect of insulin (IC₅₀ = 0.0195±.0046 min^-1). The model additionally provided an estimate of the time course of EGP showing almost immediate inhibition, followed by a secondary inhibitory effect caused by infusion of insulin, and a large overshoot as EGP returns to its basal value. Our estimates show very good agreement with those obtained via deconvolution and the model-independent TTR clamp technique. These results suggest the new integrated model can serve as a simple one-step approach to obtain metabolic indexes, while also providing a parametric description of EGP.