Background.Remodeling of the endocrine pancreas, caused by the deleterious effects of amylin as it is co-synthesized, co-packaged, and co-secreted with insulin, gives clinicians and researchers cause to ponder.Methods.A literature search was done, and relevant publications and texts on amylin and islet amyloid polypeptide (IAPP) were reviewed.Results.The mechanisms and clinical consequences attributed to the remodeling of the endocrine pancreas, along with proposals for reevaluating the methods of treating patients who have type 2 diabetes are illustrated and discussed.Conclusions.In addition to controlling the devastating effects of glucotoxicity, lipotoxicity, and hypertension, we should consider the newer hypoglycemic agents with regard to their effects on the remodeling of the endocrine pancreas. This remodeling results in structural and subsequent functional changes, causing continued elevations of hemoglobin A1C. Studies are indicated to determine whether amylin (IAPP) may be implicated in the remodeling of the arterial vessel wall, the glomerulus of the kidney, and the cardiac interstitium.