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      Dapagliflozin: a sodium glucose cotransporter 2 inhibitor in development for type 2 diabetes

      review-article
      1 , 2 , , 1 , 2
      Diabetes Therapy
      Springer Healthcare Communications
      dapagliflozin, diabetes, SGLT2, inhibitor

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          Abstract

          Type 2 diabetes mellitus (T2DM) is a growing worldwide epidemic. Patients face lifelong therapy to control hyperglycemia and prevent the associated complications. There are many medications, with varying mechanisms, available for the treatment of T2DM, but almost all target the declining insulin sensitivity and secretion that are associated with disease progression. Medications with such insulin-dependent mechanisms of action often lose efficacy over time, and there is increasing interest in the development of new antidiabetes medications that are not dependent upon insulin. One such approach is through the inhibition of renal glucose reuptake. Dapagliflozin, the first of a class of selective sodium glucose cotransporter 2 inhibitors, reduces renal glucose reabsorption and is currently under development for the treatment of T2DM. Here, we review the literature relating to the preclinical and clinical development of dapagliflozin.

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          Most cited references31

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          Metformin.

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            Pathogenesis of type 2 diabetes mellitus.

            This article provides an overview of the pathogenesis of type 2 diabetes mellitus. Discussion begins by describing normal glucose homeostasis and ingestion of a typical meal and then discusses glucose homeostasis in diabetes. Topics covered include insulin secretion in type 2 diabetes mellitus and insulin resistance, the site of insulin resistance, the interaction between insulin sensitivity and secretion, the role of adipocytes in the pathogenesis of type 2 diabetes, cellular mechanisms of insulin resistance including glucose transport and phosphorylation, glycogen and synthesis,glucose and oxidation, glycolysis, and insulin signaling.
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              SGLT2 inhibition--a novel strategy for diabetes treatment.

              Inhibiting sodium-glucose co-transporters (SGLTs), which have a key role in the reabsorption of glucose in the kidney, has been proposed as a novel therapeutic strategy for diabetes. Genetic mutations in the kidney-specific SGLT2 isoform that result in benign renal glycosuria, as well as preclinical and clinical studies with SGLT2 inhibitors in type 2 diabetes, support the potential of this approach. These investigations indicate that elevating renal glucose excretion by suppressing SGLT2 can reduce plasma glucose levels, as well as decrease weight. Although data from ongoing Phase III trials of these agents are needed to more fully assess safety, results suggest that the beneficial effects of SGLT2 inhibition might be achieved without exerting significant side effects--an advantage over many current diabetes medications. This article discusses the role of SGLT2 in glucose homeostasis and the evidence available so far on the therapeutic potential of blocking these transporters in the treatment of diabetes.
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                Author and article information

                Contributors
                a.a.tahrani@bham.ac.uk
                Journal
                Diabetes Ther
                Diabetes Therapy
                Springer Healthcare Communications (Heidelberg )
                1869-6953
                1869-6961
                19 January 2011
                19 January 2011
                December 2010
                : 1
                : 2
                : 45-56
                Affiliations
                [1 ]Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham, B9 5SS UK
                [2 ]University of Birmingham, Birmingham, UK
                Article
                7
                10.1007/s13300-010-0007-3
                3138480
                22127745
                9d5cd7be-6e74-4b10-8d30-424864ec5f9f
                © Springer Healthcare 2010
                History
                : 4 August 2010
                Categories
                Review
                Custom metadata
                © Springer Healthcare 2010

                Endocrinology & Diabetes
                inhibitor,diabetes,sglt2,dapagliflozin
                Endocrinology & Diabetes
                inhibitor, diabetes, sglt2, dapagliflozin

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