Management of Diabetes Mellitus in Acromegaly and Cushing's Disease with Focus on Pasireotide Therapy: A Narrative Review.

Patients suffering from acromegaly and Cushing's Disease (CD) face the risk of several clinical complications. The onset of diabetes mellitus (DM) is among the most important: exposure to elevated growth hormone or cortisol levels is associated with insulin resistance (IR). DM contributes to increasing cardiovascular risk for these subjects, which is higher compared to healthy individuals. Hyperglycemia may also be caused by pasireotide, a second-generation somatostatin receptor ligand (SRLs), currently used for the treatment of these diseases. Accordingly, with 2014 medical expert recommendations, the management of hyperglycemia in patients with CD and treated with pasireotide is based on lifestyle changes, metformin, DPP-4 inhibitors (DPP-4i) and, subsequently, GLP-1 Receptor Agonists (GLP-1 RAs). There is no position for SGLT2-inhibitors (SGLT2-i). However, a very recent experts' consensus regarding the management of pasireotide-induced hyperglycemia in patients with acromegaly suggests the use of GLP-1 RAs as first line treatment (in suitable patients) and the use of SGLT2-i as second line treatment in patients with high cardiovascular risk or renal disease. As a matter of fact, beyond the hypoglycemic effect of GLP1-RAs and SGLT2-i, there is increasing evidence regarding their role in the reduction of cardiovascular risk, commonly very high in acromegaly and CD and often tough to improve despite biochemical remission. So, an increasing use of GLP1-RAs and SGLT2-i to control hyperglycemia is desirable in these diseases. Obviously, all of that must be done with due attention in order to minimize the occurrence of adverse events. For this reason, large studies are needed to analyze the presence of potential limitations.