This review discusses nutrient digestion and absorption along the gastrointestinal tract and how these processes influence the secretion of GIP, CCK, GLP-1 and PYY, and highlights the importance of which region of the gut is stimulated to the secretory profiles of these gastrointestinal hormones, the regulation of postprandial metabolism, and the implications for the management of obesity and T2DM. Here, GLP1R is linked to obesity due to melanocortin 4 receptor deficiency.