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Key Points The incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are gut-derived hormones that potentiate insulin secretion and contribute to glucose metabolism through a wide range of physiological actions Inhibitors of the incretin-inactivating enzyme dipeptidyl peptidase 4 (DPP-4) and DPP-4-resistant injectable GLP-1 receptor agonists have been developed for the treatment of hyperglycaemia in type 2 diabetes mellitus (T2DM) GLP-1 and other gut-derived hormones might directly and/or indirectly regulate electrolyte and fluid homeostasis by influencing feeding and drinking behaviour as well as electrolyte transport in the kidneys and gastrointestinal tract GLP-1 receptor (GLP-1R) agonists and DPP-4 inhibitors increase natriuresis in T2DM, possibly through overlapping and distinct mechanisms, and might slightly improve renal haemodynamics in the setting of diabetes-related glomerular hyperfiltration Incretin-based therapies seem to directly influence renal physiology and have indirect metabolic and haemodynamic actions that might reduce renal risk in T2DM

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