Manuscript Muskiet, Wheeler & Heerspink New renoprotective drugs REVIEW New Pharmacological Strategies for Protecting Kidney Function in Type 2 Diabetes Marcel H.A. Muskiet MD1 David C. Wheeler MD2 Hiddo J.L. Heerspink PharmD PhD3 1 Diabetes Centre, Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands 2 Centre for Nephrology, University College London, London, United Kingdom 3 Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands Corresponding Author: David C. Wheeler MD Centre for Nephrology, University College London Rowland Hill Street, London NW3 2PF, UK Email:
[email protected] Running head: New renoprotective drugs Key words: Type 2 diabetes, diabetic kidney disease, end-stage kidney disease, renoprotection, SGLT2 inhibitors, incretin-based therapies, GLP-1 receptor agonists, DPP-4 inhibitors, mineralocorticoid receptor antagonists, endothelin receptor antagonists Word count: Summary: 164; Manuscript: 5343 Figures: 2; Tables: 3; Boxes: 2; Supplemental 0 References: 117 The Lancet Diabetes & Endocrinology Page: 1/26 Muskiet, Wheeler & Heerspink New renoprotective drugs [H1]Summary Diabetes is the leading cause of impaired kidney function, albuminuria and renal replacement therapy in virtually all regions of the world and places a large burden on health care systems. Current treatment strategies rely on intensive glucose-lowering and strict blood pressure control, targeting blockade of the renin-angiotensin-aldosterone system. Such approaches may slow decline in kidney function, but many patients progress to end-stage kidney failure despite optimal therapy. In recent clinical trials, two new-generation glucose-lowering drug classes; the sodium-glucose co-transporter (SGLT)2 inhibitors and glucagon-like peptide (GLP)-1 receptor agonists have been shown to improve both kidney and cardiovascular outcomes in patients with type 2 diabetes.