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These invasive gut surgical procedures, aimed to reduce absorptive surface area of the proximal GI tract, such as Roux-en-Y gastric by-pass (RYGB) or Sleeve Gastrectomy (SLG), are associated with an improved glycaemic control, weight loss, and often with complete remission from T2DM ( Despite this, the complete remittance of a great fraction of RYGB patients represents a fascinating new case-series that points at the importance of the EECs and its modulation of the whole-body metabolism ( A panoply of contradictory studies have attempted to establish what is the possible role of GLP-1 or other gut peptides in the rapid, and long-lasting remittance from T2D after bariatric surgery, but no consensus about the identity of the molecular players has yet been reached ( Since 2005, there are on the market only two classes of drugs that attempt to bolster glucagon-like peptide-1 signaling, GLP-1 receptor agonists and DPP-IV inhibitors, for a supra-physiological GLP-1 activity