Moreover, the stepwise administration of amylin and GLP-1R analogs was able to break the plateau normally observed with individual pharmacotherapies, even when combined from the beginning of treatment, thus supporting the hypothesis that a stepwise-introduction of a combinatorial pharmacological approach at treating obesity is more effective in achieving a sustained and long-lasting degree of weight loss. This evidence concerns the gene GLP1R and obesity due to melanocortin 4 receptor deficiency.