Reduced sensitivity to GLP-1 and GIP in adipose precursor cells and in mature fat cells in obesity-associated insulin-resistant states indicates a “GLP-1/GIP-resistant” phenotype as a potential genetic predisposing factor for the development of clinical glucose intolerance and IR (Figure 1 and Figure 2B). Here, GCG is linked to obesity due to melanocortin 4 receptor deficiency.