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      The New Biology of Diabetic Kidney Disease—Mechanisms and Therapeutic Implications

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          Abstract

          Diabetic kidney disease remains the most common cause of end-stage kidney disease in the world. Despite reductions in incidence rates of myocardial infarction and stroke in people with diabetes over the past 3 decades, the risk of diabetic kidney disease has remained unchanged, and may even be increasing in younger individuals afflicted with this disease. Accordingly, changes in public health policy have to be implemented to address the root causes of diabetic kidney disease, including the rise of obesity and diabetes, in addition to the use of safe and effective pharmacological agents to prevent cardiorenal complications in people with diabetes. The aim of this article is to review the mechanisms of pathogenesis and therapies that are either in clinical practice or that are emerging in clinical development programs for potential use to treat diabetic kidney disease.

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          Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

          The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown.
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            Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes

            Establishing cardiovascular safety of new therapies for type 2 diabetes is important. Safety data are available for the subcutaneous form of the glucagon-like peptide-1 receptor agonist semaglutide but are needed for oral semaglutide.
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              The biology of incretin hormones.

              Gut peptides, exemplified by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted in a nutrient-dependent manner and stimulate glucose-dependent insulin secretion. Both GIP and GLP-1 also promote beta cell proliferation and inhibit apoptosis, leading to expansion of beta cell mass. GLP-1, but not GIP, controls glycemia via additional actions on glucose sensors, inhibition of gastric emptying, food intake and glucagon secretion. Furthermore, GLP-1, unlike GIP, potently stimulates insulin secretion and reduces blood glucose in human subjects with type 2 diabetes. This article summarizes current concepts of incretin action and highlights the potential therapeutic utility of GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of type 2 diabetes.
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                Author and article information

                Journal
                Endocrine Reviews
                The Endocrine Society
                0163-769X
                1945-7189
                April 2020
                April 01 2020
                April 2020
                April 01 2020
                October 21 2019
                : 41
                : 2
                : 202-231
                Affiliations
                [1 ]Department of Medicine, Division of Nephrology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
                [2 ]Department of Medicine, Division of Nephrology, Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, Colorado
                [3 ]Diabetes Center, Department of Internal Medicine, VU University Medical Center, Netherlands
                [4 ]The George Institute for Global Health, Sydney, Australia
                [5 ]Department of Clinical Pharmacology, University of Groningen, Groningen, Netherlands
                Article
                10.1210/endrev/bnz010
                7156849
                31633153
                90539f76-4984-4f08-b0ca-a71cf8c5e4d0
                © 2019

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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