Diabetes Metab Syndr Obes. 2013 Nov 27;6:453-67. doi: 10.2147/DMSO.S34416.
SGLT-2 inhibitors and their potential in the treatment of diabetes.
Diabetes, metabolic syndrome and obesity : targets and therapy
Rebecca F Rosenwasser, Senan Sultan, David Sutton, Rushab Choksi, Benjamin J Epstein
Affiliations
Affiliations
- East Coast Institute for Research, Jacksonville, FL, USA.
- Northeast Florida Endocrine and Diabetes Associates, Jacksonville, FL, USA.
- Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA.
PMID: 24348059
PMCID: PMC3848644 DOI: 10.2147/DMSO.S34416
Abstract
Diabetes remains a burgeoning global problem, necessitating ongoing efforts on the part of pharmaceutical and device manufacturers, patients, and society to curb the frightening trends in morbidity and mortality attributable to the malady. Since 1835 when phlorizin was discovered, sodium glucose co-transporter 2 (SGLT-2) inhibitors have rested tantalizingly on the horizon, promising a more physiological approach to glucose control. These agents lower glucose by enhancing its excretion by blocking reabsorption in the renal tubules, thus eliminating glucose from the body along with the molecules' attendant effects on caloric balance, plasma osmolality, and lipids. Consequently, SGLT-2 inhibitors improve glucose control to an extent comparable to other hypoglycemic agents while simultaneously reducing body weight, blood pressure, and cholesterol - an admirable portfolio. One agent, canagliflozin, has recently been approved by the US Food and Drug Administration (FDA) and two other agents have progressed through Phase III trials, including dapagliflozin and empagliflozin. Collectively, when used as monotherapy, these agents have demonstrated reductions in hemoglobin A1c (HbA1c), body weight, and blood pressure of -0.34% to -1.03%, -2.0 to -3.4 kg, and -1.7 to -6.4 mmHg/-0.3 to -2.6 mmHg (systolic blood pressure/diastolic blood pressure), respectively. SGLT-2 inhibitors have been well tolerated, with hypoglycemia (0.9% to 4.3%) occurring infrequently in clinical trials. Safety signals related to breast and bladder cancer have arisen with dapagliflozin, though these are unsubstantiated and likely ascribed to the presence of preexisting cancer. As these agents emerge, clinicians should embrace the addition to the formulary for treating type 2 diabetes, but must also weight the risk-benefit of this new class in deciding which patient types are most likely to benefit from their novel mechanism of action.
Keywords: canagliflozin; dapagliflozin; diabetes; empagliflozin; sodium–glucose transporter 2
References
- Diabetes Obes Metab. 2012 Oct;14(10):951-9 - PubMed
- Diabetes Care. 2010 Oct;33(10):2217-24 - PubMed
- Eur J Pediatr. 2013 Mar;172(3):409-11 - PubMed
- Eur J Endocrinol. 2012 Apr;166(4):711-6 - PubMed
- Rheum Dis Clin North Am. 2006 May;32(2):313-31, vi - PubMed
- Diabetes Care. 2009 Apr;32(4):650-7 - PubMed
- Diab Vasc Dis Res. 2012 Apr;9(2):117-23 - PubMed
- Am J Physiol Regul Integr Comp Physiol. 2012 Jan 1;302(1):R75-83 - PubMed
- Lancet. 2012 Feb 11;379(9815):507 - PubMed
- Pflugers Arch. 2013 Jan;465(1):153-65 - PubMed
- Diabetes Educ. 2010 Jul-Aug;36 Suppl 3:44S-72S; quiz 73S-74S - PubMed
- Diabetes Obes Metab. 2009 Feb;11(2):79-88 - PubMed
- J Clin Endocrinol Metab. 2012 Mar;97(3):1020-31 - PubMed
- Ann Intern Med. 2012 Mar 20;156(6):405-15 - PubMed
- Diabetes Care. 2011 Sep;34(9):2015-22 - PubMed
- Diabetes Obes Metab. 2011 Oct;13(10):928-38 - PubMed
- Pharmacol Ther. 2013 Jul;139(1):51-9 - PubMed
- Nat Rev Drug Discov. 2010 Jul;9(7):551-9 - PubMed
- Curr Diab Rep. 2012 Jun;12(3):230-8 - PubMed
- Diabetes Obes Metab. 2010 Jun;12(6):510-6 - PubMed
- Diabetes Care. 2012 Jul;35(7):1473-8 - PubMed
- Am J Kidney Dis. 2009 May;53(5):875-83 - PubMed
- Postgrad Med. 2011 Jul;123(4):38-45 - PubMed
- Heart. 2013 Jun;99(11):759-66 - PubMed
- Br J Clin Pharmacol. 2013 Sep;76(3):432-44 - PubMed
- Diabetes Care. 2013 Aug;36(8):2271-9 - PubMed
- Drug Saf. 2009;32(3):187-202 - PubMed
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