To test the hypothesis that food intake reduction after glucagon‐like peptide‐1 (GLP‐1) receptor activation is mediated through brain areas regulating anticipatory and consummatory food reward.

As part of a larger study, we determined the effects of GLP‐1 receptor activation on brain responses to anticipation and receipt of chocolate milk versus a tasteless solution, using functional MRI (fMRI). Obese subjects with type 2 diabetes, and obese and lean subjects with normoglycaemia (n = 48) underwent three fMRI sessions at separate visits with intravenous infusion of the GLP‐1 receptor agonist exenatide, exenatide with prior GLP‐1 receptor blockade by exendin‐9‐39 or placebo, during somatostatin pituitary‐pancreatic clamps.

Body mass index negatively correlated with brain responses to receipt of chocolate milk and positively correlated with anticipation of receipt of chocolate milk in brain areas regulating reward, appetite and motivation. Exenatide increased brain responses to receipt of chocolate milk and decreased anticipation of receipt of chocolate milk compared with placebo, paralleled by reductions in food intake. Exendin‐9‐39 largely prevented these effects.

Our findings show that GLP‐1 receptor activation decreases anticipatory food reward, which may reduce cravings for food and increases consummatory food reward, which may prevent overeating.