Use of Sodium Glucose Cotransporter 2 Inhibitors in the Hands of Cardiologists

• cardiovascular diseases
• diabetes mellitus
• heart failure
• kidney
• prevention and control
• sodium-glucose transporter 2

The EMPA-REG OUTCOME trial (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) showed beneficial effects of a sodium glucose cotransport-2 inhibitor (SGLT2i) on overall and cardiovascular mortality and heart failure (HF) hospitalizations in patients with type 2 diabetes mellitus.¹ It is important to note that the benefits of empagliflozin were observed in patients across chronic kidney disease stages despite an expected attenuation of its hemoglobin A_1c–lowering effects in patients with an estimated glomerular filtration rate <60 mL·min⁻¹·1.73 m⁻². While the mechanisms responsible for these benefits with an SGLT2i are being elucidated, the results of this pivotal study will inevitably affect clinical cardiology practice. Moreover, given the apparent glucose-independent effects of empagliflozin on cardiovascular outcomes,¹ cardiologists may wish to recommend or prescribe an SGLT2i for patients with type 2 diabetes mellitus who have prevalent atherosclerotic cardiovascular disease. Recommendations for SGLT2is in cardiology guidelines will further empower frontline cardiologists. However, SGLT2is are relatively new medications, until now prescribed primarily by primary care clinicians and endocrinologists. Hence, many cardiologists are not yet familiar with the benefits and risks of these agents.

Accordingly, the aim of this Perspective is to provide an overview of the mechanism of action and side-effect profile of SGLT2is and specifically to provide guidance for SGLT2i use when combined with diuretics. We are concerned about the potential for untoward ramifications of broad-based, untargeted use of a new cardioprotective therapy with potential for additive side effects from concomitant cardiorenal therapies such as diuretics.² The risk for such events is usually higher than reported in clinical trials of select patients and investigators, which may lead to a negative profile and lost opportunity.

The SGLT2is decrease hemoglobin A_{1c …}