The efficiency of glucose and insulin control on glucose production (EGP) plays an important role in glucose homeostasis and its derangement in diabetes. Therefore the ability to accurately quantify indices of the individual role of glucose (GEL) and insulin (SIL) in the suppression of EGP would allow to improve the understanding of liver metabolism. Measuring these indices by minimal modelling of tracer labelled and unlabelled glucose data is often unreliable, possibly due to an inadequate description of EGP included in the minimal model (EGPMM). Moreover a validation of EGPMM on EGP data has never been done. Here EGPMM and alternative EGP descriptions were tested on recent model-independent EGP data of 20 subjects obtained with a triple-tracer meal protocol. Model performances were compared in terms of data fit and physiological plausibility. EGP MM was not able to describe EGP data, while one of the new model showed a good fit and provided accurate and precise estimates of hepatic sensitivity indices: GEL=0.013 ± 0.001 dl/kg/min; S IL =5.71 ± 0.48 10-4 dl/kg/min per μU/ml (36% and 41%, respectively, of total sensitivity indices GE TOT and SITOT). This novel approach will allow to enhance our understanding of the role of the liver in pathophysiological states.