title: The gut-renal axis: do incretin-based agents confer renoprotection in diabetes?
abstract: Diabetic nephropathy is the leading cause of end-stage renal disease worldwide, and is associated with a high risk of cardiovascular morbidity and mortality. Intensive control of glucose levels and blood pressure is currently the mainstay of both prevention and treatment of diabetic nephropathy. However, this strategy cannot fully prevent the development and progression of diabetic nephropathy, and an unmet need remains for additional novel therapies. The incretin-based agents--agonists of glucagon-like peptide 1 receptor (GLP-1R) and inhibitors of dipeptidyl peptidase 4 (DPP-4), an enzyme that degrades glucagon-like peptide 1--are novel blood-glucose-lowering drugs used in the treatment of type 2 diabetes mellitus (T2DM). Therapeutic agents from these two drug classes improve pancreatic islet function and induce extrapancreatic effects that ameliorate various phenotypic defects of T2DM that are beyond glucose control. Agonists of GLP-1R and inhibitors of DPP-4 reduce blood pressure, dyslipidaemia and inflammation, although only GLP-1R agonists decrease body weight. Both types of incretin-based agents inhibit renal tubular sodium reabsorption and decrease glomerular pressure as well as albuminuria in rodents and humans. In rodents, incretin-based therapies also prevent onset of the morphological abnormalities of diabetic nephropathy.
authors.affiliation: Diabetes Centre, Department of Internal Medicine, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands.
authors.forename: Marcel H A
authors.initials: MH
authors.lastname: Muskiet
authors.affiliation: Diabetes Centre, Department of Internal Medicine, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Smits
authors.affiliation: Diabetes Centre, Department of Internal Medicine, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands.
authors.forename: Linde M
authors.initials: LM
authors.lastname: Morsink
authors.affiliation: Diabetes Centre, Department of Internal Medicine, VU University Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands.
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D054795:Incretins