Neuronal GLP1R mediates liraglutide's anorectic but not glucose-lowering effect.

Liraglutide increases insulin sensitivity and lowers blood glucose levels after fasting and after meals in people with obesity and prediabetes by activating GLP-1 receptors, without requiring weight loss and differently from how DPP-4 inhibitors or dieting affect glucose.

In mice, liraglutide reduces appetite and body weight only if neuronal GLP1 receptors are present; when these receptors are absent, the drug has no effect on food intake or weight, but still improves glucose tolerance.

In mice, liraglutide lowers blood glucose through direct action on the pancreas, not through nerve signals from the brain or vagus nerve, even when those nerve receptors are absent.

In mice, liraglutide causes a learned avoidance of a specific flavor only if GLP1 receptors in neurons are present; when these receptors are absent, the mice do not avoid the flavor, showing that brain GLP1 receptors are necessary for this behavioral effect.

In mice, removing GLP1 receptors from the brain does not change how body weight or food intake is regulated, whether the mice eat a normal diet or a high-fat diet.

In mice, removing GLP1 receptors from nerves connecting the gut to the brain does not stop liraglutide from reducing food intake, showing that the brain's direct response to the drug, not signals from the gut, causes the reduction in eating.