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Diabetes Management SGLT2 Inhibitors
threshold. However, SGLT2 inhibitors act independently of pancreatic specifically, the safety of SGLT2 inhibitors used in combination with
beta-cell insulin secretion and are dependent on plasma glucose blood pressure medications is of particular concern. Finally, it would
levels; as glucose levels decrease, so does the amount of glucosuria. be of considerable interest to evaluate the efficacy of these drugs in
The risk for hypoglycemia is therefore low in patients receiving SLGT2 type 1 diabetes to possibly expand the indications for which these
inhibitor treatment. inhibitors are applicable.
The use of an SGLT2 inhibitor will invariably result in glucosuria, making Summary and Conclusion
it necessary to ensure that this does not lead to any adverse events for With the increasing prevalence of type 2 diabetes worldwide, it is
the patient. Microbiological pathogens, particularly bacteria, proliferate becoming more important for researchers to develop new and more
at sites abundant in sugar, and it was hypothesized that glucosuria may effective drugs for its treatment. SGLT2 inhibitors represent a novel class
lead to increased urinary tract infections. However, this was not of agents under investigation that target the reabsorption of glucose by
observed, and the only negative effect reported in some studies was a the kidney, in contrast to traditional approaches that involve increasing
slightly higher incidence of fungal infections of the vagina, which can insulin secretion to reduce hyperglycemia and improve glycemic
easily be treated with antibiotics.
35
In addition, SGLT2 inhibitors do not control. By selectively inhibiting SGLT2, these oral drugs can potentially
appear to negatively affect kidney organ function despite altering the reduce plasma glucose levels and glucose toxicity without causing any
rate of glucose reabsorption. serious adverse events, with a low risk of hypoglycemia. SGLT2
inhibitors should therefore be a welcome addition to the currently
Future Developments available treatment options for type 2 diabetes. n
Based on the studies conducted on the various SGLT2 inhibitors, it is
reasonable to believe that these drugs can be added to any diabetes
Serge A Jabbour, MD, FACP, FACE, is an Associate
treatment regimen. Currently, the standard first-line therapy for type
Professor of Medicine and Interim Director of the Division
2 diabetes is metformin, due to its low cost and favorable safety of Endocrinology, Diabetes, and Metabolic Diseases in the
profile.
37
SGLT2 inhibitors could become second-line therapy, and
Department of Medicine at Jefferson Medical College of
Thomas Jefferson University in Philadelphia. He is a
could possibly replace metformin as the first-line therapy. In addition
member of numerous professional organizations,
to acting as an effective monotherapy, SGLT2 inhibitors can also including The Endocrine Society, the American Diabetes
be safely given in combination with other established diabetes
Association (ADA), and the American Association of
Clinical Endocrinologists (AACE). Dr Jabbour is involved in
medications, including sulfonylureas and insulin. SGLT2 inhibitors are
many clinical trials related to new drugs in the field of diabetes and has lectured across
therefore believed to be appropriate for adding to the currently the US on various endocrine topics, mainly diabetes, in the setting of grand rounds,
available treatment combinations.
symposia, or other continuing medical education (CME) presentations. He has published
many articles on diabetes and metabolic syndrome, serves on the Editorial Board of
many journals, and is Section Editor for diabetes and metabolic diseases for the
As SGLT2 inhibitors proceed into the later stages of development, International Journal of Clinical Practice. Dr Jabbour was named ‘Top Doc in
certain key issues remain that need to be addressed. In particular, the
Endocrinology’ by Philadelphia Magazine in 2002 and he is the holder of many teaching
awards, including Teacher of the Year 2002–2003. He completed his fellowship in
safety of these drugs needs to be verified. This class of medication has
endocrinology, diabetes, and metabolism at Thomas Jefferson University in 1999, and has
proved to be effective in reducing HbA
1c
levels; however, overall drug been on faculty at Thomas Jefferson University ever since.
safety is still a major concern for physicians and patients alike. More
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2. ADA, Diabetes Care, 2009;32(Suppl. 1):S13–61. 14. Kanai Y, et al., J Clin Invest, 1994;93:397–404. Annual Scientific Session, Chicago, US, 2007;0491-P.
3. Brooks AM, Thacker SM, Ann Pharmacother, 2009;43:1286–93. 15. Wright EM, et al., J Intern Med, 2007;261:32–43. 29. Hussey EK, et al., American Diabetes Association, 67th
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6. Chan JM, et al., Diabetes Care, 1994;17:961–9. 20. Magen D, et al., Kidney Int, 2005;67:34–41. 33. Komoroski B, et al., Clin Pharmacol Ther, 2009;85:520–26.
7. Colditz GA, et al., Ann Intern Med, 1995;122:481–6. 21. Francis J, et al., Nephrol Dial Transplant, 2004;19:2893–5. 34. Komoroski B, et al., Clin Pharmacol Ther, 2009;85:513–19.
8. Diabetes Atlas Committee, Diabetes Atlas, 2nd edn, 2003. 22. Rossetti L, et al., J Clin Invest, 1987;80:1037–44. 35. Bailey CJ, et al., European Association for the Study of
9. Idris I, Donnelly R, Diabetes Obes Metab, 2009;11:79–88. 23. Jabbour SA, Goldstein BJ, Int J Clin Pract, 2008;62:1279–84. Diabetes (EASD), 45th Annual Meeting, Vienna, 2009;
10. Wright EM, Am J Physiol Renal Physiol, 2001;280:F10–18. 24. Tsujihara K, et al., J Med Chem, 1999;42:5311–24. 169-OP 29.
11. Gerich JE, Diabetes Obes Metab, 2000;2:345–50. 25. Adachi T, et al., Metabolism, 2000;49:990–95. 36. Handlon AL, et al., Expert Opin Ther Patents, 2005;15:1531–40.
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78 US ENDOCRINOLOGY
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