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.

doi:10.1111/jcpt.12077

Cited by 35Diabetes Treatment and ManagementDiabetes Management and ResearchPharmacology and Obesity Treatment

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

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Cangoz, S., Chang, Y.-Y., Chempakaseril, S. J., Guduru, R. C., Huynh, L. M., John, J. S., John, S. T., Joseph, M. E. +10 more·2013·Journal of Clinical Pharmacy and Therapeutics

DOI 10.1111/jcpt.12077

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Abstract

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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SGLT2 inhibitors lower blood glucose by preventing glucose and sodium reabsorption in the proximal tubule.
“Sodium/glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels by preventing glucose and sodium reabsorption in the proximal tubule (8–10).”
From SGLT2 inhibition for CKD and cardiovascular disease in type 2 diabetes: report of a scientific workshop sponsored by the National Kidney Foundation (2021) · cites this paper as [10]

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Authors: 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.
Affiliations: Temple University (US)
Corresponding author: Raffa, R. B.
ORCID: John, J. S.
Raffa, R. B.
Venue: Journal of Clinical Pharmacy and Therapeutics
Publisher: Hindawi Limited
Published: 2013-06-12
Volume: 38
Issue: 5
Pages: 350-359
ISSN: 0269-4727 (ISSN-L)
DOI: 10.1111/jcpt.12077
OpenAlex: W2093048828
Cited by: 35
References: 109
Citations by year: 2025: 1 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 5
FWCI: 0.59
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm)
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Clinical Pharmacy and Therapeutics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
Keywords: SGLT2 inhibitors, renal glucose reabsorption, antidiabetic drugs, type 2 diabetes, hyperglycemia, HbA1c reduction, drug efficacy, drug safety, breast cancer risk, bladder cancer risk, insulin-independent glucose regulation
MeSH terms: Sodium-Glucose Transporter 2 Inhibitors, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Kidney, Sodium-Glucose Transporter 2

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

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