SGLT2 inhibition in diabetes mellitus: rationale and clinical prospects
- 7 February 2012
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Endocrinology
- Vol. 8 (8), 495-502
- https://doi.org/10.1038/nrendo.2011.243
Abstract
This Review covers the rationale, physiological consequences and clinical application of pharmacological sodium-glucose cotransporter 2 (SGLT2) inhibition. In patients with type 2 diabetes mellitus, in whom renal glucose reabsorption might be upregulated, orally active, selective SGLT2 inhibitors improve glycaemic control to a therapeutically useful extent. Chronic administration of several SGLT2 inhibitors dose-dependently lowers HbA(1c) levels by 0.5-1.5% without causing hypoglycaemia. The unique mechanism of action of SGLT2 inhibitors-which does not hinge upon β-cell function or tissue insulin sensitivity-means that they can exert their antihyperglycaemic effects in combination with any other oral antidiabetic drug as well as insulin. Available phase III studies confirm a good tolerability profile. Weight loss owing to urinary calorie leakage may be less than expected, but the negative energy balance offers a valuable clinical benefit. Offloading of sodium can assist blood pressure control. The progressive loss of efficacy in patients with reduced glomerular function will have to be balanced against the possibility of renal protection. The safety issues of genitourinary infections and cancer risk requires careful, proactive monitoring and analysis of robust exposure data, particularly in elderly, frail patients and in patients with impaired kidney function and/or high cardiovascular/cancer risk, who represent an increasing fraction of the population with diabetes mellitus.Keywords
This publication has 69 references indexed in Scilit:
- Biology of Human Sodium Glucose TransportersPhysiological Reviews, 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
- Glucose transport by human renal Na+/d-glucose cotransporters SGLT1 and SGLT2American Journal of Physiology-Cell Physiology, 2011
- Functional expression of SGLTs in rat brainAmerican Journal of Physiology-Cell Physiology, 2010
- SGLT1, a novel cardiac glucose transporter, mediates increased glucose uptake in PRKAG2 cardiomyopathyJournal of Molecular and Cellular Cardiology, 2010
- HbA1c and mean blood glucose show stronger associations with cardiovascular disease risk factors than do postprandial glycaemia or glucose variability in persons with diabetes: the A1C-Derived Average Glucose (ADAG) studyDiabetologia, 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
- Emerging treatment options for type 2 diabetesBritish Journal of Clinical Pharmacology, 2010
- Facilitative glucose transporter 9, a unique hexose and urate transporterAmerican Journal of Physiology-Endocrinology and Metabolism, 2009