Renoprotection in diabetic kidney disease: can incretin-based therapies deliver?

Abstract

PURPOSE OF REVIEW\nIncretin-based therapies mimic or augment the gut-hormone glucagon-like peptide (GLP)-1 and, due to their glucose-lowering potential and beneficial safety profile, as well as their cardiovascular safety and/or protection, are prescribed on a large scale to treat individuals with type 2 diabetes (T2D). However, whether the two drug-classes that belong to this category, respectively GLP-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors, also reduce the risk of diabetic kidney disease (DKD) is at present heavily debated. This review aims to discuss the current evidence.\n\n\nRECENT FINDINGS\nEvidence from land-mark cardiovascular safety trials, conducted in people with T2D at high-cardiovascular risk but with normal kidney function, suggest that both drug-classes have excellent renal safety profiles. In contrast to DPP-4 inhibitors, it seems that GLP-1 receptor agonists reduce albuminuria and possibly induce a reduction of estimated glomerular filtration rate decline. However, the trials were not properly designed to test renal outcomes.\n\n\nSUMMARY\nA dedicated renal trial involving a GLP-1 receptor agonist has recently commenced and will answer the question whether these drugs will be effective to reduce DKD. Moreover, ongoing mechanism-of-action studies are focusing on the renal physiological effects of GLP-1, as the effects on particularly albuminuria reduction remain currently unexplained.