Objective-Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like. Peptide-1 (GLP-1) have additive insulinotropic effects when coadministered in health. We aimed to determine whether GIP confers additional glucose lowering to that of GLP-1 in the critically ill. Research design and methods-Twenty mechanically ventilated critically ill patients without known diabetes were studied in a prospective, randomized, double-blind, crossover fashion on 2 consecutive days. Between T0 and T420 minutes, GLP-1 (1.2 pmol/kg z min21) was infused intravenously with either GIP (2 pmol/kg z min21) or 0.9% saline. Between T60 and T420 minutes, nutrient liquid was infused into the small intestine at 1.5 kcal/min. Results-Adding GIP did not alter blood glucose or insulin responses to small intestinal nutrient. GIP increased glucagon concentrations slightly before nutrient delivery (P50.03), but not thereafter. Conclusions-The addition of GIP to GLP-1 does not result in additional glucose-lowering or insulinotropic effects in critically ill patients with acute-onset hyperglycemia.