The Role of Sodium-Glucose Co-Transporter 2 Inhibitors in the Treatment of Type 2 Diabetes

Karen Whalen, Shannon Miller, Erin St Onge
Clinical Therapeutics 2015 June 1, 37 (6): 1150-66

PURPOSE: Diabetes is a chronic metabolic disorder characterized by hyperglycemia that results from insulin resistance, diminished or absent insulin secretion, or both. Approximately one-half of patients with diabetes fail to achieve acceptable glycemic control. Consequently, morbidity and mortality associated with diabetes is high, resulting from complications such as cardiovascular disease and nephropathy. The sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of medications for the treatment of type 2 diabetes. This article provides an overview of efficacy and safety data for the SGLT2 inhibitors and outlines their role in the management of diabetes.

METHODS: Relevant articles were identified through searches of PubMed and International Pharmaceutical Abstracts by using the key terms canagliflozin, dapagliflozin, empagliflozin, and sodium-glucose co-transporter 2 inhibitor. A review of bibliographies of retrieved articles was also performed to identify additional references. All identified trials published in English and that involved the efficacy and safety of SGLT2 inhibitors in the treatment of type 2 diabetes were reviewed.

FINDINGS: The SGLT2 inhibitors improve glucose control by increasing urinary glucose excretion. Effectiveness is decreased in the presence of renal dysfunction. These agents are efficacious as monotherapy and add-on therapy for patients with type 2 diabetes uncontrolled on metformin, sulfonylureas, insulin, and other antihyperglycemic combinations. The SGLT2 inhibitors lower glycosylated hemoglobin by 0.5% to 1% and fasting plasma glucose by ~15 to 35 mg/dL, depending on the agent and the dosage used, and are also associated with modest reductions in weight (-1.5 to -3.5 kg) and systolic blood pressure (-3 to -5 mm Hg). Genital mycotic infections and increased urination, owing to the mechanism of action, are the most common adverse effects. In general, the class is well tolerated, and the risk of hypoglycemia is low.

IMPLICATIONS: With their unique mechanism of action and good safety and tolerability profiles, the SGLT2 inhibitors are an important addition to existing treatments for type 2 diabetes. Because of the lack of data with this class of drugs when current treatment guidelines for diabetes were published, the SGLT2 inhibitors are recommended as second- or third-line therapies for diabetes. Forthcoming data on the long-term efficacy and safety profile of these agents should help to solidify the role of SGLT2 inhibitors in the management of diabetes.

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