Sodium-glucose co-transporter 2 (SGLT2) inhibitors: a growing class of anti-diabetic agents

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Although several treatment options are available to reduce hyperglycemia, only about half of individuals with diagnosed diabetes mellitus (DM) achieve recommended glycemic targets. New agents that reduce blood glucose concentrations by novel mechanisms and have acceptable safety profiles are needed to improve glycemic control and reduce the complications associated with type 2 diabetes mellitus (T2DM). The renal sodium-glucose co-transporter 2 (SGLT2) is responsible for reabsorption of most of the glucose filtered by the kidney. Inhibitors of SGLT2 lower blood glucose independent of the secretion and action of insulin by inhibiting renal reabsorption of glucose, thereby promoting the increased urinary excretion of excess glucose. Canagliflozin, dapagliflozin, and empagliflozin are SGLT2 inhibitors approved as treatments for T2DM in the United States, Europe, and other countries. Canagliflozin, dapagliflozin, and empagliflozin increase renal excretion of glucose and improve glycemic parameters in patients with T2DM when used as monotherapy or in combination with other antihyperglycemic agents. Treatment with SGLT2 inhibitors is associated with weight reduction, lowered blood pressure, and a low intrinsic propensity to cause hypoglycemia. Overall, canagliflozin, dapagliflozin, and empagliflozin are well tolerated. Cases of genital infections and, in some studies, urinary tract infections have been more frequent in canagliflozin-, dapagliflozin-, and empagliflozin-treated patients compared with those receiving placebo. Evidence from clinical trials suggests that SGLT2 inhibitors are a promising new treatment option for T2DM.

Keywords: administration, oral; canagliflozin; dapagliflozin; diabetes mellitus, type 2; drug therapy; empagliflozin; antidiabetic agents; sodium-glucose co-transporter 2

Abbreviations: AACE, American Association of Clinical Endocrinologists; ACEI, angiotensin-converting enzyme inhibitor; AE, adverse event; ARB, angiotensin receptor blocker; BP, blood pressure; CKD, chronic kidney disease; DBP, diastolic blood pressure; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; EU, European Union; FPG, fasting plasma glucose; GFR, glomerular filtration rate; HbA1c, glycated hemoglobin; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; PPG, postprandial glucose; SBP, systolic blood pressure; t1/2, half-life; T2DM, type 2 diabetes mellitus; US, United States

Vivian EM. Sodium-glucose co-transporter 2 (SGLT2) inhibitors: a growing class of antidiabetic agents. Drugs in Context 2014; 3: 212264. doi: 10.7573/dic.212264

© 2014 Vivian EM. Distributed under the terms of the Creative Commons License Deed CC BY NC ND 3.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No other uses without permission.

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Copyright © Vivian EM. Published by Drugs in Context under Creative Commons Attributions License Deed CC BY NC ND 3.0.

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Eva M Vivian, PharmD, MS, BC-ADM, CDE, Associate Professor, School of Pharmacy, University of Wisconsin, Madison, WI, USA.

Submitted, externally peer reviewed

Submitted: 3 September 2014
Accepted, subject to peer review: 4 September 2014
Peer review comments to author: 18 September 2014
Revised manuscript submitted: 10 November 2014
Publication date: 19 December 2014

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