The rise of GIP from enterogastrone to major metabolic hormone makes an interesting story (Marks 2020), but the answer is largely due to the well-known insensitivity of humans with obesity and obesity-driven T2DM to the insulinotropic and glucose-lowering actions of GIP (Nauck et al. 2021b). Here, GIP is linked to obesity due to melanocortin 4 receptor deficiency.