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The kidney as a new target for antidiabetic drugs: SGLT 2 inhibitors
Author(s) -
Cangoz S.,
Chang Y.Y.,
Chempakaseril S. J.,
Guduru R. C.,
Huynh L. M.,
John J. S.,
John S. T.,
Joseph M. E.,
Judge R.,
Kimmey R.,
Kudratov K.,
Lee P. J.,
Madhani I. C.,
Shim P. J.,
Singh S.,
Singh S.,
Ruchalski C.,
Raffa R. B.
Publication year - 2013
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12077
Subject(s) - medicine , renal glucose reabsorption , adverse effect , insulin , diabetes mellitus , clinical trial , pharmacology , type 2 diabetes , drug , intensive care medicine , bioinformatics , endocrinology , biology
Summary What is known and objective A novel class of antidiabetic drugs – SGLT 2 (Na + /glucose cotransporter type 2) inhibitors – target renal reabsorption of glucose and promote normal glucose levels, independent of insulin production or its action at receptors. We review this new mechanistic approach and the reported efficacy and safety of clinical testing of lead compounds. Methods Information was obtained from various bibliographic sources, including PubMed and others, on the basic science and the clinical trials of SGLT 2 inhibitors. The information was then summarized and evaluated from the perspective of contribution to a fuller understanding of the potential and current status of the lead clinical candidates. Results and discussion Diabetes mellitus is a spectrum of disorders that involves inadequate insulin function resulting in adverse health sequelae due to acute and chronic hyperglycaemia. Current antidiabetic pharmacotherapy primarily addresses either insulin production at the pancreatic β‐cells or insulin action at insulin receptors. These drugs have less than full clinical effectiveness and sometimes therapy‐limiting adverse effects. The third major component of glucose balance, namely elimination, has not been a significant therapeutic target to date. SGLT 2 inhibitors are a novel approach. What is new and conclusion A sufficient number of clinical trials have been conducted on sufficiently chemically diverse SGLT 2 inhibitors to reasonably conclude that they have efficacy (HbA1c reductions of 0·4–1%), and thus far, the majority of adverse effects have been mild and transitory or treatable, with the caveat of possible association with increased risk of breast cancer in women and bladder cancer in men.