title: Nephroprotection by Hypoglycemic Agents: Do We Have Supporting Data?
abstract: Current therapy directed at delaying the progression of diabetic nephropathy includes intensive glycemic and optimal blood pressure control, renin angiotensin-aldosterone system blockade and multifactorial intervention. However, the renal protection provided by these therapeutic modalities is incomplete. There is a scarcity of studies analysing the nephroprotective effect of antihyperglycaemic drugs beyond their glucose lowering effect and improved glycaemic control on the prevention and progression of diabetic nephropathy. This article analyzes the exisiting data about older and newer drugs as well as the mechanisms associated with hypoglycemic drugs, apart from their well known blood glucose lowering effect, in the prevention and progression of diabetic nephropathy. Most of them have been tested in humans, but with varying degrees of success. Although experimental data about most of antihyperglycemic drugs has shown a beneficial effect in kidney parameters, there is a lack of clinical trials that clearly prove these beneficial effects. The key question, however, is whether antihyperglycemic drugs are able to improve renal end-points beyond their antihyperglycemic effect. Existing experimental data are post hoc studies from clinical trials, and supportive of the potential renal-protective role of some of them, especially in the cases of dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. Dedicated and adequately powered renal trials with renal outcomes are neccessary to assess the nephrotection of antihyperglycaemic drugs beyond the control of hyperglycaemia.
authors.affiliation: Hospital Universitario Dr Peset, Universidad de Valencia, Valencia 46017, Spain. jlgorriz@senefro.org.|GEENDIAB, Diabetic Nephropathy Working Group of the Spanish Society of Nephrology, Spain. jlgorriz@senefro.org.|Carlos III Research Institute, Madrid 28029, Spain. jlgorriz@senefro.org.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Górriz
authors.affiliation: Hospital General Universitario de Ciudad Real, Ciudad Real, 13005 Ciudad Real, Spain. ljnietoi@gmail.com.|GEENDIAB, Diabetic Nephropathy Working Group of the Spanish Society of Nephrology, Spain. ljnietoi@gmail.com.
authors.forename: Javier
authors.initials: J
authors.lastname: Nieto
authors.affiliation: Hospital Universitario N S Candelaria, Tenerife 38010, Spain. jnavgon@gobiernodecanarias.org.|GEENDIAB, Diabetic Nephropathy Working Group of the Spanish Society of Nephrology, Spain. jnavgon@gobiernodecanarias.org.|Carlos III Research Institute, Madrid 28029, Spain. jnavgon@gobiernodecanarias.org.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Navarro-González
authors.affiliation: Hospital Universitario Dr Peset, Universidad de Valencia, Valencia 46017, Spain. molina_pab@gva.es.
authors.forename: Pablo
authors.initials: P
authors.lastname: Molina
authors.affiliation: Hospital Universitario Bellvitge, IDIBELL, Barcelona 08907, Spain. albertomcastelao@gmail.com.|GEENDIAB, Diabetic Nephropathy Working Group of the Spanish Society of Nephrology, Spain. albertomcastelao@gmail.com.|Carlos III Research Institute, Madrid 28029, Spain. albertomcastelao@gmail.com.
authors.forename: Alberto
authors.initials: A
authors.lastname: Martínez-Castelao
authors.affiliation: Hospital Universitario Dr Peset, Universidad de Valencia, Valencia 46017, Spain. pallardo_lmi@gva.es.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Pallardó
keywords: DDP4 inhibitors; SGLT2 inhibition; albuminuria; antihyperglycemic drugs; diabetes mellitus; diabetic chronic kidney disease; diabetic nephropathy; glucagon-like peptide agonists; nephroprotection