INS and obesity due to melanocortin 4 receptor deficiency: In contrast with the improved insulin sensitivity seen after chronic GLP-1 or exendin-4 treatment in human patients with extreme obesity [64] or T2DM [65], insulin sensitivity was profoundly decreased on the 11th day of exendin-4 treatment in neonatal IUGR lambs, relative to their untreated IUGR littermates.