Real-Life Prescribing of SGLT2 Inhibitors: How to Handle the Other Medications, Including Glucose-Lowering Drugs and Diuretics

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have emerged as an effective therapy for improving outcomes in diabetic and nondiabetic kidney disease (1,2). Clinical trials have demonstrated the benefits of SGLT2is for secondary prevention of adverse cardiovascular (CV) effects in patients with established atherosclerotic disease and/or heart failure with reduced ejection fraction (3⇓⇓⇓–7). It is imperative for clinicians to assess the use of SGLT2is in medically eligible patients and prescribe these agents when appropriate. Despite the overwhelming evidence of the benefits of SGLT2i therapy, the prescription rate remains dismally low, particularly among patients most likely to benefit from cardiorenal protective effects (8). Several potential factors contribute to low SGLT2i prescription rate, including prescriber hesitancy, treatment inertia, and high drug cost. In this article, we review clinical indications for SGLT2i use, therapeutic and adverse effects, and our approach to handling concomitant medications. The use of SGLT2is is clinically indicated in the following circumstances. 1. Type 2 diabetes mellitus (T2DM) and albuminuric kidney disease (albuminuria of ≥200 mg/g of creatinine plus eGFR of 25–90 ml/min per 1.73 m2). In the CREDENCE Trial, canagliflozin decreased the primary cardiorenal end point by 30%, compared with placebo, in patients with diabetic kidney disease (1). In the DAPA-CKD trial, dapagliflozin reduced the primary cardiorenal end point by 39%, compared with placebo, in patients with diabetic and nondiabetic kidney disease (2). 2. Nondiabetic albuminuric kidney disease (albuminuria ≥200 mg/d plus eGFR of 25–75 ml/min per 1.73 m2). In the DAPA-CKD trial, a third of the patients did not have T2DM, and the cardiorenal benefits of dapagliflozin were similar among patients with nondiabetic and diabetic kidney disease (2). 3. T2DM with CV disease. In the EMPA-REG and CANVAS trials, empagliflozin and canagliflozin demonstrated a 14% reduction in the primary end point of major …