The kidney as a new target for antidiabetic drugs: SGLT2 inhibitors
Open Access
- 12 June 2013
- journal article
- review article
- Published by Hindawi Limited in Journal of Clinical Pharmacy & Therapeutics
- Vol. 38 (5), 350-359
- https://doi.org/10.1111/jcpt.12077
Abstract
What is known and objective A novel class of antidiabetic drugs – SGLT2 (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 SGLT2 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. SGLT2 inhibitors are a novel approach. What is new and conclusion A sufficient number of clinical trials have been conducted on sufficiently chemically diverse SGLT2 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.Keywords
This publication has 98 references indexed in Scilit:
- Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exerciseDiabetes, Obesity and Metabolism, 2013
- A Clinical Trial to Maintain Glycemic Control in Youth with Type 2 DiabetesThe New England Journal of Medicine, 2012
- Minireview: Epigenetics of Obesity and Diabetes in HumansEndocrinology, 2012
- Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trialDiabetes, Obesity and Metabolism, 2011
- Evaluation of the effect of dapagliflozin on cardiac repolarization: a thorough QT/QTc studyDiabetes Therapy, 2011
- Diminished glucagon suppression after β-cell reduction is due to impaired α-cell function rather than an expansion of α-cell massAmerican Journal of Physiology-Endocrinology and Metabolism, 2011
- TS-071 is a novel, potent and selective renal sodium-glucose cotransporter 2 (SGLT2) inhibitor with anti-hyperglycaemic activityBritish Journal of Pharmacology, 2011
- Genotyping analysis of Helicobacter pylori using multiple-locus variable-number tandem-repeats analysis in five regions of China and JapanBMC Microbiology, 2011
- 10-Year Follow-up of Intensive Glucose Control in Type 2 DiabetesThe New England Journal of Medicine, 2008
- Survival of Cancer Cells Is Maintained by EGFR Independent of Its Kinase ActivityCancer Cell, 2008