SGLT2 Inhibitors: 5 Things You Should Know

The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin was approved by the FDA on August 1, 2014, joining canagliflozin and dapagliflozin in the newest class of oral antihyperglycemic drugs indicated for the treatment of type 2 diabetes. These agents block the reabsorption of glucose form the proximal renal tubules and so act independently of insulin levels. They are appropriate for use at all stages of disease-not affected by beta cell function or insulin sensitivity.The slides above offer snapshots of the known advantages and disadvantages of the SGLT2 inhibitors. Links to additional information can be found in the reference list below.

References:

Slide 1
1. Nair S, Joseph F, Ewins D, Wilding J, Goenka N. From history to reality: sodium glucose co-transporter 2 inhibitors – a novel therapy for type 2 diabetes mellitus. Pract Diabetes Int. 2010;27:311–16.

Slide 2 
1. Wilding JPH, Woo V, Rohwedder K, Sugg  J, Parikh S; for the Dapagliflozin 006 Study Group. Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years. Diabetes Obes Metab. 2014;16:124–136. doi: 10.1111/dom.12187

2. Forst T, Guthrie R, Goldenberg  R, et al. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone. Diabetes Obes  Metab. 2014 Feb 15. doi: 10.1111/dom.12273. [Epub ahead of print]

3. Valentine V. The role of the kidney and sodium-glucose cotransporter 2 inhibition in diabetes management. Clin Diabetes. 2012;30:151-155. doi: 10.2337/diaclin.30.4.151

4. Rosenstock J, Seman L J,  Jelaska  A, et al. Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia.Diabetes Obes Metab. 2014; 15: 1154–1160. doi: 10.1111/dom.12185

5.  Goring  S, Hawkins N, Wygant G, et al.   Dapagliflozin compared with other oral anti-diabetes treatments when added to metformin monotherapy: a systematic review and network meta-analysis. Diabetes Obes  Metab.  2013 Nov 14. doi: 10.1111/dom.12239. [Epub ahead of print]

Slide 3
1.  Wilding JPH, Woo V, Rohwedder K, Sugg  J, Parikh S; for the Dapagliflozin 006 Study Group. Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years. Diabetes Obes Metab. 2014;16:124–136. doi: 10.1111/dom.12187 http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1111%2Fdom.12187

2.  Rosenstock J, Seman L J,  Jelaska  A, et al. Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia. Diabetes Obes Metab. 2014; 15: 1154–1160. doi: 10.1111/dom.12185

Slide 4
1. Wilding JPH, Woo V, Rohwedder K, Sugg  J, Parikh S; for the Dapagliflozin 006 Study Group. Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years. Diabetes Obes Metab. 2014;16:124–136. doi: 10.1111/dom.12187

2.  Rosenstock J, Seman L J,  Jelaska  A, et al. Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia. Diabetes Obes Metab. 2014; 15: 1154–1160. doi: 10.1111/dom.12185 http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1111%2Fdom.12185

3. Forst T, Guthrie R, Goldenberg  R, et al. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone Diabetes Obes  Metab. 2014 Feb 15. doi: 10.1111/dom.12273. [Epub ahead of print]

4. Cefalu WT, Leiter A, Yoon KH, et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet. 2103;382:941-950.

5. Johnsson KM, Ptaszynska A, Schmitz B, Sugg J, Parikh SJ, List JM. Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin.  J Diabetes Complications. 2013;27:479-484. doi: 10.1016/j.jdiacomp.2013.04.012

6. Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium glucose cotransporter 2 inhibition in type 2 diabetic patients.  J Clin Invest. 2014;124:499-508.

7. Merovci A, Solis-Herrera C, Daniele G, et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.  J Clin Invest. 2014;124:509-514.