The kidney as a new target for antidiabetic drugs: SGLT2 inhibitors

S. Cangoz, Y. Y. Chang, S. J. Chempakaseril, R. C. Guduru, L. M. Huynh, J. S. John, S. T. John, M. E. Joseph, R. Judge, R. Kimmey, K. Kudratov, P. J. Lee, I. C. Madhani, P. J. Shim, S. Singh, S. Singh, C. Ruchalski, R. B. Raffa

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

Summary What is known and objective A novel class of antidiabetic drugs - SGLT2 (Na+/glucose cotransporter type 2) inhibitors - target renal reabsorption of glucose and promote normal glucose levels, independent of insulin production or its action at receptors. We review this new mechanistic approach and the reported efficacy and safety of clinical testing of lead compounds. Methods Information was obtained from various bibliographic sources, including PubMed and others, on the basic science and the clinical trials of SGLT2 inhibitors. The information was then summarized and evaluated from the perspective of contribution to a fuller understanding of the potential and current status of the lead clinical candidates. Results and discussion Diabetes mellitus is a spectrum of disorders that involves inadequate insulin function resulting in adverse health sequelae due to acute and chronic hyperglycaemia. Current antidiabetic pharmacotherapy primarily addresses either insulin production at the pancreatic β-cells or insulin action at insulin receptors. These drugs have less than full clinical effectiveness and sometimes therapy-limiting adverse effects. The third major component of glucose balance, namely elimination, has not been a significant therapeutic target to date. SGLT2 inhibitors are a novel approach. What is new and conclusion A sufficient number of clinical trials have been conducted on sufficiently chemically diverse SGLT2 inhibitors to reasonably conclude that they have efficacy (HbA1c reductions of 0·4-1%), and thus far, the majority of adverse effects have been mild and transitory or treatable, with the caveat of possible association with increased risk of breast cancer in women and bladder cancer in men.

Original languageEnglish (US)
Pages (from-to)350-359
Number of pages10
JournalJournal of Clinical Pharmacy and Therapeutics
Volume38
Issue number5
DOIs
StatePublished - Oct 1 2013
Externally publishedYes

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Hypoglycemic Agents
Insulin
Kidney
Glucose
Clinical Trials
Insulin Receptor
PubMed
Urinary Bladder Neoplasms
Hyperglycemia
Diabetes Mellitus
Breast Neoplasms
Safety
Drug Therapy
Health
Therapeutics
Pharmaceutical Preparations

Keywords

  • diabetes
  • inhibitor
  • pharmacotherapy
  • sodium/glucose transport

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Cangoz, S., Chang, Y. Y., Chempakaseril, S. J., Guduru, R. C., Huynh, L. M., John, J. S., ... Raffa, R. B. (2013). The kidney as a new target for antidiabetic drugs: SGLT2 inhibitors. Journal of Clinical Pharmacy and Therapeutics, 38(5), 350-359. https://doi.org/10.1111/jcpt.12077

The kidney as a new target for antidiabetic drugs : SGLT2 inhibitors. / Cangoz, S.; Chang, Y. Y.; Chempakaseril, S. J.; Guduru, R. C.; Huynh, L. M.; John, J. S.; John, S. T.; Joseph, M. E.; Judge, R.; Kimmey, R.; Kudratov, K.; Lee, P. J.; Madhani, I. C.; Shim, P. J.; Singh, S.; Singh, S.; Ruchalski, C.; Raffa, R. B.

In: Journal of Clinical Pharmacy and Therapeutics, Vol. 38, No. 5, 01.10.2013, p. 350-359.

Research output: Contribution to journalReview article

Cangoz, S, Chang, YY, Chempakaseril, SJ, Guduru, RC, Huynh, LM, John, JS, John, ST, Joseph, ME, Judge, R, Kimmey, R, Kudratov, K, Lee, PJ, Madhani, IC, Shim, PJ, Singh, S, Singh, S, Ruchalski, C & Raffa, RB 2013, 'The kidney as a new target for antidiabetic drugs: SGLT2 inhibitors', Journal of Clinical Pharmacy and Therapeutics, vol. 38, no. 5, pp. 350-359. https://doi.org/10.1111/jcpt.12077
Cangoz S, Chang YY, Chempakaseril SJ, Guduru RC, Huynh LM, John JS et al. The kidney as a new target for antidiabetic drugs: SGLT2 inhibitors. Journal of Clinical Pharmacy and Therapeutics. 2013 Oct 1;38(5):350-359. https://doi.org/10.1111/jcpt.12077
Cangoz, S. ; Chang, Y. Y. ; Chempakaseril, S. J. ; Guduru, R. C. ; Huynh, L. M. ; John, J. S. ; John, S. T. ; Joseph, M. E. ; Judge, R. ; Kimmey, R. ; Kudratov, K. ; Lee, P. J. ; Madhani, I. C. ; Shim, P. J. ; Singh, S. ; Singh, S. ; Ruchalski, C. ; Raffa, R. B. / The kidney as a new target for antidiabetic drugs : SGLT2 inhibitors. In: Journal of Clinical Pharmacy and Therapeutics. 2013 ; Vol. 38, No. 5. pp. 350-359.
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AU - Guduru, R. C.

AU - Huynh, L. M.

AU - John, J. S.

AU - John, S. T.

AU - Joseph, M. E.

AU - Judge, R.

AU - Kimmey, R.

AU - Kudratov, K.

AU - Lee, P. J.

AU - Madhani, I. C.

AU - Shim, P. J.

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N2 - Summary What is known and objective A novel class of antidiabetic drugs - SGLT2 (Na+/glucose cotransporter type 2) inhibitors - target renal reabsorption of glucose and promote normal glucose levels, independent of insulin production or its action at receptors. We review this new mechanistic approach and the reported efficacy and safety of clinical testing of lead compounds. Methods Information was obtained from various bibliographic sources, including PubMed and others, on the basic science and the clinical trials of SGLT2 inhibitors. The information was then summarized and evaluated from the perspective of contribution to a fuller understanding of the potential and current status of the lead clinical candidates. Results and discussion Diabetes mellitus is a spectrum of disorders that involves inadequate insulin function resulting in adverse health sequelae due to acute and chronic hyperglycaemia. Current antidiabetic pharmacotherapy primarily addresses either insulin production at the pancreatic β-cells or insulin action at insulin receptors. These drugs have less than full clinical effectiveness and sometimes therapy-limiting adverse effects. The third major component of glucose balance, namely elimination, has not been a significant therapeutic target to date. SGLT2 inhibitors are a novel approach. What is new and conclusion A sufficient number of clinical trials have been conducted on sufficiently chemically diverse SGLT2 inhibitors to reasonably conclude that they have efficacy (HbA1c reductions of 0·4-1%), and thus far, the majority of adverse effects have been mild and transitory or treatable, with the caveat of possible association with increased risk of breast cancer in women and bladder cancer in men.

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