Sodium-Glucose Cotransporter 2 Inhibitors: Possible Role in Cardiology

Long-term treatment goals in type 2 diabetes should focus on the reduction of micro- and macro-vascular complications. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an emerging antidiabetic class that offer significant cardiovascular risk reduction.

In a study recently published in the Journal of Cardiology, a research group at the Japanese College of Cardiology investigated the impact of SGLT2 inhibitors on the future of cardiovascular (CV) medicine.

SGLT2 inhibitors work by inhibiting glucose reabsorption at the renal proximal tubule, resulting in urinary glucose excretion. HbA_1c is reduced by 0.7% to 1%, and many patients experience a weight loss of 3 to 4 kg.

The EMPA-REG OUTCOME trial investigated SGLT2 inhibitors’ CV safety. Empagliflozin demonstrated risk reductions in CV death, overall mortality, and hospitalizations due to worsening heart failure. These benefits are most likely due to their natriuretic action, but researchers still need to delineate exact mechanisms.

These agents regulate both systemic and renal hemodynamics by lowering blood pressure, depleting plasma volume, and modulating renal function. Improved glycemic control and weight loss due to glycosuria may also benefit CV outcomes in the long term.

Evidence suggests potential benefits when used in patients with heart failure, especially in conjunction with RAAS inhibitors. Antiatherosclerotic potential has been demonstrated in animal models, and researchers are currently conducting randomized clinical trials to assess this potential benefit.

Early intervention with SGLT2 inhibitors may slow progression of impaired glucose intolerance and diabetes, and contribute to improved CV outcomes. It is unknown if these results are attributable to a class-effect or if they are trial-specific. Currently, 3 ongoing CV safety trials are underway. Thus, the authors concluded that health care clinicians should familiarize themselves with SGLT2 inhibitors, and consider their use to improve CV outcomes and mortality.

Reference

Tanaka A, Node K. Emerging roles of sodium—glucose cotransporter 2 inhibitors in cardiology. J Cardiol. 2016; http://dx.doi.org/10.1016/j.jjcc.2016.10.019.