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

GLP-1 in addiction medicine: GLP-1 acts on pancreas, gut, kidney, heart and thyroid receptors to activate reward/stress hubs (VTA, NAc, ARC, PFC, hypothalamus)
The reasoning was two-fold: The higher metformin dose may actually help with the constipation, and the two drugs work synergistically they complement each other in ways that can enhance overall effectiveness
8 Just like GLP-1, the GIP (glucose-dependent insulinotropic polypeptide) pathway is activated primarily after meals, but performs different functions
This information can help you and your healthcare provider determine whether mood changes are truly medication-related or attributable to other factors