The impact of the GLP-1 receptor agonist lixisenatide on postprandial glucose disposition was examined in conscious dogs, to identify mechanisms for its improvement of meal tolerance in humans and examine the tissue disposition of meal-derived carbohydrate. Catheterization for measurement of hepatic balance occurred 16d before study. After fasting overnight, dogs received a subcutaneous injection of lixisenatide 1.5 µg/kg or vehicle (saline; Control), n=6/group. Thirty minutes later, they received an oral meal feeding (93.4 kJ; 19% protein, 71% glucose polymers, and 10% lipid). Acetaminophen was included in the meal in 4 Control and 5 Lixisenatide dogs for assessment of gastric emptying. Observations continued for 510 min; absorption was incomplete in Lixisenatide at that point. The plasma acetaminophen AUC in Lixisenatide was 65% of that in Control (P<0.05). Absorption of the meal began within 15 min in Control but was delayed until 30-45 min in Lixisenatide. Lixisenatide reduced (P<0.05) the postprandial arterial glucose AUC 54% and insulin AUC 44%. Net hepatic glucose uptake did not differ significantly between groups. Nonhepatic glucose uptake tended to be reduced by lixisenatide (6151±4321 and 10541±1854 µmol/kg•510 min in Lixisenatide and Control, P=0.09), but adjusted (for glucose and insulin concentrations), values did not differ (18.9±3.8 and 19.6±7.9 l/kg÷pmol/l, Lixisenatide and Control, respectively; P=0.94). Thus, lixisenatide delays gastric emptying, allowing more efficient disposal of the carbohydrate in the feeding, without increasing liver glucose disposal. Lixisenatide could prove to be a valuable adjunct in treatment of postprandial hyperglycemia in impaired glucose tolerance or type 2 diabetes.