Sodium–glucose cotransporter 2 inhibitors: an evidence-based practice approach to their use in the natural history of type 2 diabetes

Abstract

Objective The sodium–glucose cotransporter 2 (SGLT-2) inhibitors are an important addition to available treatments for patients with type 2 diabetes (T2D) as an adjunct to modifications in diet and exercise. SGLT-2 inhibitors may be prescribed alone or as add-on treatment in patients receiving metformin, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and/or insulin across the natural history of the disease. Inhibition of SGLT-2, which is responsible for approximately 90% of renal glucose reabsorption, increases urinary glucose excretion and lowers blood glucose concentrations. The objective of this review is to discuss the pathophysiology of diabetes and the contribution of the kidney to glucose homeostasis and to provide an evidence-based practice approach to clinical applications of SGLT-2 inhibitors in the treatment of T2D.

Methods PubMed and Google Scholar databases were searched to identify literature published from 1990 through September 2015 examining the pathophysiology of T2D, the role of the kidney in regulating glucose concentrations, and clinical evidence for the efficacy and safety of SGLT-2 inhibitors in T2D.

Results There is a need for early treatment in patients with T2D to minimize the risk of cardiovascular complications that increase morbidity and mortality. SGLT-2 inhibitors improve glycemic control, reduce body weight and blood pressure, and are associated with a low risk of hypoglycemia. Adverse events associated with SGLT-2 inhibitors include mild to moderate urinary tract and genital infections and mild dehydration potentially leading to orthostatic hypotension.

Conclusions An evidence-based practice approach to examining the importance of early, proactive treatment of T2D using SGLT-2 inhibitors from initiation of pharmacotherapy to increasingly more complicated combination therapy regimens, including insulin, suggests that this treatment strategy maximizes benefits and minimizes potential side effects. The SGLT-2 inhibitors augment the arsenal of available antidiabetes agents, facilitating the ability of clinicians to design tailored treatment regimens that help patients achieve therapeutic goals.

Keywords:

• Canagliflozin
• Dapagliflozin
• Empagliflozin
• Evidence-based practice approach
• Sodium–glucose cotransporter 2 inhibitor
• Type 2 diabetes

Declaration of funding

AstraZeneca funded medical writing support for the preparation of this manuscript, and agents of the sponsors reviewed the manuscript. All authors contributed to and approved this manuscript.

Declaration of financial/other relationships

S.S.S. has disclosed that he has served as an advisory board member for Janssen, Merck, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Salix, Novo Nordisk, Takeda, and Genesis Biotechnology Group and on the speakers bureaus of Takeda, Janssen, Merck, Novo Nordisk, Salix, Boehringer Ingelheim, Eli Lilly, Eisai, AstraZeneca, GlaxoSmithKline, and Amgen. I.A. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work. CMRO peer reviewer 1 has disclosed that he is a consultant to AbbVie and Janssen and is on the speakers bureaus of AstraZeneca and Roche. CMRO peer reviewer 2 has disclosed that he is the recipient of research/grant funding from GlaxoSmithKline, Novartis, Novo Nordisk, Takeda, AstraZeneca, NIH, sanofi-aventis, Eli Lilly and Daiichi-Sankyo; is a consultant to, and lecturer for, GlaxoSmithKline, Novartis, Takeda, sanofi-aventis, Eli Lilly and Daiichi Sankyo; and is on the speakers bureaus for Novo Nordisk and sanofi-aventis.

Acknowledgments

Editorial support was provided by Scarlett Geunes-Boyer PhD and Janet E. Matsuura PhD of Complete Healthcare Communications LLC, and was funded by AstraZeneca.