The Ethics of Conducting Clinical Trials With Sodium-Glucose Cotransporter-2 Inhibitors in Heart Failure: Is Placebo Assignment Justified in Patients With Comorbid Diabetes Mellitus and Heart Failure?
Abstract
everal randomized clinical trials have recently started enrolling patients or are in the planning stages to assess the impact of treatment with various sodiumglucose cotransporter-2 (SGLT2) inhibitors in patients with heart failure, many of whom will have comorbid diabetes mellitus.The impetus for these trials comes from the EMPA-REG OUTCOME trial (Empaglifozin-Reducing Excess Glucose CV Outcomes), in which treatment with empagliflozin in patients with type II diabetes mellitus with a known history of cardiovascular diseases was shown to lower the risk of cardiovascular death by 38%. 1 This led to the US Food and Drug Administration approval of a new indication for empagliflozin, ie, "to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease."Also, the 2016 European Society of Cardiology heart failure guidelines issued a IIa-B recommendation stating that "empagliflozin should be considered in patients with type 2 diabetes mellitus in order to prevent or delay the onset of heart failure or prolong life."No recommendation was made for treatment in patients with established heart failure.Recently, the CVD-REAL study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) assessing the impact of 3 different SGLT2 inhibitors in real-life clinical practice from 6 different countries also showed mortality benefit with these agents in patients with diabetes mellitus. 2Although the…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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