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Review
. 2020 Mar 30;9(4):947.
doi: 10.3390/jcm9040947.

GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Call of Attention to Nephrologists

José Luis Górriz  1 , María José Soler  2 , Juan F Navarro-González  3 , Clara García-Carro  2 , María Jesús Puchades  1 , Luis D'Marco  1 , Alberto Martínez Castelao  4 , Beatriz Fernández-Fernández  5 , Alberto Ortiz  4 , Carmen Górriz-Zambrano  6 , Jorge Navarro-Pérez  7 , Juan José Gorgojo-Martinez  8
Affiliations
Review

GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Call of Attention to Nephrologists

José Luis Górriz et al. J Clin Med. .

Abstract

Type 2 diabetes mellitus (T2DM) represents the main cause of chronic kidney disease (CKD) and end-stage renal disease (ESKD), and diabetic kidney disease (DKD) is a major cause of morbidity and mortality in diabetes. Despite advances in the nephroprotective treatment of T2DM, DKD remains the most common complication, driving the need for renal replacement therapies (RRT) worldwide, and its incidence is increasing. Until recently, prevention of DKD progression was based around strict blood pressure (BP) control, using renin-angiotensin system blockers that simultaneously reduce BP and proteinuria, adequate glycemic control and control of cardiovascular risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a new class of anti-hyperglycemic drugs shown to improve cardiovascular and renal events in DKD. In this regard, GLP-1RA offer the potential for adequate glycemic control in multiple stages of DKD without an increased risk of hypoglycemia, preventing the onset of macroalbuminuria and slowing the decline of glomerular filtration rate (GFR) in diabetic patients, also bringing additional benefit in weight reduction, cardiovascular and other kidney outcomes. Results from ongoing trials are pending to assess the impact of GLP-1RA treatments on primary kidney endpoints in DKD.

Keywords: GLP-1; chronic kidney disease; diabetic kidney disease.

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Conflict of interest statement

J.L.G. has served as consultant for Boëhringer-Ingelheim, Mundipharma, AstraZeneca, Novonordisk and has received speaker honoraria from Boëhringer-Ingelheim, Mundipharma, AstraZeneca, Novonordisk, Novartis and Eli Lilly. M.J.S. reports personal fees and has served on advisory boards from NovoNordisk, Jansen, Boëhringer-Ingelheim, Mundipharma, AstraZeneca, and Esteve, during the study period. J.F.N.G. has served as a consultant, has received speaker fees or travel support from Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Esteve, Genzyme, Lilly, Novartis, Servier, Shire and Vifor Fresenius Medical Care, Renal Pharma. C.G.C. reports speaker honoraria and has served on advisory boards from Astra Zeneca and Boehringer Ingelheim and travel support from Astellas, Menarini, Novartis, Esteve, Sanofi and Novonordisk. MJP declares no conflicts of interest. L.D.M. declares no conflicts of interest. A.M.C. declares speaker honoraria from Boëhringer-Ingelheim, Lilly, Novo-Nordisk, M.S.D. and Esteve, and advisory boards for Boëhringer-Ingelheim, Lilly, M.S.D. B.F.F. reports personal speaker fees from Mundipharma, Esteve and Novartis; has received travel support from Abbvie, Amgen, Menarini, Novartis, Novonordisk and Esteve, and has served as an advisory board consultant from Astrazeneca, Boehringer Ingelheim and Mundipharma outside the submitted work. A.O. has served as a consultant for Mundipharma, Sanofi Genzyme and Freeline and has received speaker honoraria from Amgen, Amicus, Otsuka and Fresenius Medical Care. C.G.Z. declares no conflicts of interest. J.N.P. has served as consultant for Sanofi and declares speaker honoraria from Boëhringer-Ingelheim, AstraZeneca, Eli Lilly and a research grant from Boëhringer-Ingelheim. J.J.G.M. has served as a consultant for AstraZeneca, Janssen Pharmaceuticals, Eli Lilly and Company, Merck Sharp and Dohme, Mundipharma, Novo Nordisk and Pfizer; has given lectures for Abbott, AbbVie Inc, AstraZeneca, Boehringer Ingelheim Pharmaceuticals Inc, Esteve, Janssen Pharmaceuticals, Eli Lilly and Company, Merck Sharp and Dohme, Novo Nordisk, Pfizer, Roche Pharma and Sanofi Aventis, and has conducted research activities for AstraZeneca, Novo Nordisk and Sanofi Aventis.

Figures

Figure 1
Figure 1
Potential mechanisms for the cardio-nephroprotective effect of GLP-1RA (modified from: Thomas [39] and Greco [40].
Figure 2
Figure 2
GLP-1RA RCT studies with known beneficial cardiovascular endpoints. Blue bars—percentage of 3-point MACE reduction with the intervention drug. Orange bars—percentage of individual primary cardiovascular endpoint reduction with the intervention drug. Three-point MACE, 3-point MACE; MI, fatal and nonfatal myocardial infarction.
Figure 3
Figure 3
GLP-1RA RCT studies with known beneficial renal endpoints. Blue bars—percentage of composite renal endpoint reduction with the intervention drug. Orange bars—percentage of individual renal endpoint reduction with the intervention drug. Renal, combined renal endpoint; MA, macroalbuminuria; ↓ eGFR ≥ 40%, Sustained decline in eGFR of ≥40%; ↓ eGFR ≥ 50%, Sustained decline in eGFR of ≥50%.
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