Renal sodium glucose cotransporter 2 inhibitors as a novel therapeutic approach to treatment of type 2 diabetes: Clinical data and mechanism of action
Open Access
- 2 April 2014
- journal article
- review article
- Published by Wiley in Journal of Diabetes Investigation
- Vol. 5 (3), 265-275
- https://doi.org/10.1111/jdi.12214
Abstract
Type 2 diabetes is characterized by impaired insulin secretion from pancreatic β‐cells and/or reduced response of target tissues to insulin. Good glycemic control delays the development and slows the progression of micro‐ and macrovascular complications. Although there are numerous glucose‐lowering agents in clinical use, only approximately half of type 2 diabetic patients achieve glycemic control, and undesirable side‐effects often hamper treatment in those treated with the medications. There is a need for novel treatment options that can help overcome these difficulties. Sodium glucose cotransporter 2 (SGLT2) inhibitors have recently been developed as a novel potential therapeutic option for the treatment of type 2 diabetes. These drugs lower the plasma glucose concentration through inhibition of glucose reuptake in the kidney, independent of insulin secretion and insulin action, with a consequent lower risk of hypoglycemia. The data of clinical trials with monotherapy as well as combination therapy show that SGLT2 inhibitors have a blood glucose‐lowering effect and also reduce bodyweight. A follow‐up study shows long‐term efficacy and the durability of these effects. SGLT2 inhibitors have the potential to reverse glucose toxicity, and to improve insulin resistance, blood pressure and lipid profile. The available data suggest a good tolerability profile. However, clinicians should carefully prescribe these drugs in light of already reported and/or unexpected side‐effects. Further studies in larger numbers and longer‐term clinical use data are required to place these agents in standard treatment of type 2 diabetes.Keywords
This publication has 71 references indexed in Scilit:
- Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trialDiabetologia, 2013
- Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exerciseDiabetes, Obesity and Metabolism, 2013
- Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetesBMJ Open, 2012
- LX4211, a Dual SGLT1/SGLT2 Inhibitor, Improved Glycemic Control in Patients With Type 2 Diabetes in a Randomized, Placebo-Controlled TrialClinical Pharmacology & Therapeutics, 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
- National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participantsThe Lancet, 2011
- Biology of Human Sodium Glucose TransportersPhysiological Reviews, 2011
- Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family membersDiabetes Therapy, 2010
- Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trialThe Lancet, 2010
- 10-Year Follow-up of Intensive Glucose Control in Type 2 DiabetesNew England Journal of Medicine, 2008