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Renoprotection in diabetic kidney disease

can incretin-based therapies deliver?

van Baar, Michaël J.B.; van Raalte, Daniël H.

Current Opinion in Nephrology and Hypertension: January 2020 - Volume 29 - Issue 1 - p 103–111
doi: 10.1097/MNH.0000000000000559
HORMONES, AUTACOIDS, NEUROTRANSMITTERS AND GROWTH FACTORS: Edited by Mark Cooper and Merlin Thomas
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Purpose of review Incretin-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.

Recent findings Evidence 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.

Summary A 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.

Department of Internal Medicine, Diabetes Center, Amsterdam University Medical Centers, Amsterdam, The Netherlands

Correspondence to Daniël H. van Raalte, MD, PhD, Department of Internal Medicine, Diabetes Center, Amsterdam University Medical Centers, VUMC, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Tel: +31 20 4440534; e-mail: d.vanraalte@amsterdamumc.nl

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