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      Improving the residual risk of renal and cardiovascular outcomes in diabetic kidney disease: A review of pathophysiology, mechanisms, and evidence from recent trials


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          Based on global estimates, almost 10% of adults have diabetes, of whom 40% are estimated to also have chronic kidney disease (CKD). Almost 2 decades ago, treatments targeting the renin‐angiotensin system (RAS) were shown to slow the progression of kidney disease. More recently, studies have reported the additive benefits of antihyperglycaemic sodium‐glucose co‐transporter‐2 inhibitors in combination with RAS inhibitors on both CKD progression and cardiovascular outcomes. However, these recent data also showed that patients continue to progress to kidney failure or die from kidney‐ or cardiovascular‐related causes. Therefore, new agents are needed to address this continuing risk. Overactivation of the mineralocorticoid (MR) receptor contributes to kidney inflammation and fibrosis, suggesting that it is an appropriate treatment target in patients with diabetes and CKD. Novel, selective non‐steroidal MR antagonists are being studied in these patients, and the results of two large recently completed clinical trials have shown that one such treatment, finerenone, significantly reduces CKD progression and cardiovascular events compared with standard of care. This review summarizes the pathogenic mechanisms of CKD in type 2 diabetes and examines the potential benefit of novel disease‐modifying agents that target inflammatory and fibrotic factors in these patients.

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          Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

          Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes.
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            Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

            The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown.
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              Dapagliflozin in Patients with Chronic Kidney Disease

              Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known.

                Author and article information

                Diabetes Obes Metab
                Diabetes Obes Metab
                Diabetes, Obesity & Metabolism
                Blackwell Publishing Ltd (Oxford, UK )
                01 December 2021
                March 2022
                : 24
                : 3 ( doiID: 10.1111/dom.v24.3 )
                : 365-376
                [ 1 ] Division of Endocrinology and Metabolism Jacobs School of Medicine and Biomedical Sciences, University at Buffalo Buffalo New York USA
                [ 2 ] Diabetes Center Kaleida Health Buffalo New York USA
                [ 3 ] Buffalo VA Medical Center Jacobs School of Medicine and Biomedical Sciences, University at Buffalo Buffalo New York USA
                Author notes
                [*] [* ] Correspondence

                Ajay Chaudhuri, MD, Division of Endocrinology and Metabolism, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Williamsville, NY 14221.

                Email: chaudhuri.endo@ 123456gmail.com

                © 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                Page count
                Figures: 4, Tables: 1, Pages: 12, Words: 8947
                Funded by: Bayer , doi 10.13039/501100019189;
                Award ID: N/A
                Review Article
                Review Articles
                Custom metadata
                March 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:20.07.2022

                Endocrinology & Diabetes
                albuminuria,diabetes mellitus,diabetic nephropathies,glomerular filtration rate,mineralocorticoid receptor antagonist,renal insufficiency,chronic,renin‐angiotensin system,sodium‐glucose co‐transporter‐2 inhibitors


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