Diabetes & Metabolism Journal | 2019
An Age of Sodium-Glucose Cotransporter-2 Inhibitor Priority: Are We Ready?
Abstract
Corresponding author: Ji A Seo https://orcid.org/0000-0002-1927-2618 Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, 123 Jeokgeum-ro, Danwon-gu, Ansan 15355, Korea E-mail: [email protected] Over the past decade, the use of dipeptidyl peptidase-4 (DPP4) inhibitors in Korea has steadily increased, replacing sulfonylurea as the most commonly used add-on drug for metformin because of its low risk of hypoglycemia and its relatively better glucose-lowering effect among Asians [1,2]. However, DPP-4 inhibitors have not shown beneficial cardiovascular effects beyond safety in randomized controlled clinical trials among type 2 diabetes mellitus (T2DM) patients [3,4]. In contrast, followed by the striking results of the EMPA-REG OUTCOME study (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) [5], a series of clinical trials demonstrated the protective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiovascular and renal complications [6-8]. Thus, most updated treatment guidelines recommend SGLT2 inhibitors to be considered as the preferred choice for T2DM patients with atherosclerotic cardiovascular disease, heart failure, nephropathy, or multiple risk factors [9,10]; SGLT2 inhibitors are accordingly being used in an increasing number of Korean T2DM patients. Today, there is even a practical guide to help doctors who are not experts in T2DM treatment to prescribe SGLT2 inihibitors to protect against cardiovascular and kidney complications in T2DM patients with high cardiovascular risk [11]. Indeed, it is the age of SGLT2 inhibitors in T2DM drugs. In Diabetes & Metabolism Journal, Hong et al. [12] investigated short-term effects of SGLT2 inhibitors in the real-world setting of one general hospital in Korea. Although the analysis was performed only in a 3-month retrospective design, they confirmed good glucose-lowering efficacy of SGLT2 inhibitors as an add-on drug (–0.94% of glycosylated hemoglobin [HbA1c] change) under various anti-diabetic drug combinations including quadruple therapy, consistent with a previous study [13]. In addition, when changed from other anti-diabetic drugs to SGLT2 inhibitors (switch therapy), an overall –0.42% HbA1c lowering effect was observed. This is slightly better than the results of previous meta-analysis in which SGLT2 inhibitors appeared minimally more potent than DPP-4 inhibitors [14]. Real-world evidence as used in this study has weaknesses and uses. Considering the selection bias, it is desirable to target many subjects in various clinical conditions from various institutions. The decision to select or change a certain medication might have been easier in situations in which clinicians expected the treatment to have more positive effects. For example, SGLT2 inhibitors would have been preferable in obese patients with renal or cardiovascular risk. Moreover, the consequences of switching therapy in this study might have included specific clinical situations, resulting in drug switches (e.g., side effects on existing drugs). Nevertheless, the results of switching therapy to SGLT2 inhibitors are interesting because doctors often experience clinical situations in which they want to change prescriptions to SGLT2 inhibitors for various reasons including glucose control. Moreover, switching therapy may be a relatively common use pattern in Korea, where insurance coverage is restricted by number of drug classes used. Editorial Clinical Diabetes & Therapeutics