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Cardiovascular complications remain two to four times more common among patients with type 2 diabetes than among persons without diabetes.1 Observational studies have suggested that patients with type 2 diabetes who require insulin have increased rates of cardiovascular events.1–3 However, a large clinical trial involving patients with impaired fasting glucose levels, impaired glucose tolerance, or type 2 diabetes reported cardiovascular outcomes among those who received basal insulin glargine that were similar to outcomes among patients who received standard care.4
Degludec is an ultralong-acting, once-daily basal insulin approved for use in adults, adolescents, and children with diabetes.5–7 Previous open-label studies have shown lower day-to-day variability in the glucose-lowering effect and lower rates of hypoglycemia among the patients who received degludec than among those who received glargine.8,9 The Food and Drug Administration (FDA) required that a dedicated preapproval trial of cardiovascular outcomes be conducted to assess the cardiovascular safety of degludec, as compared with glargine. Consequently, we conducted the Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE).
Methods
Trial Design and Oversight
Detailed methods of the trial have been published previously.10 Briefly, the trial was a treat-to-target, randomized, double-blind, active comparator–controlled cardiovascular outcomes trial that was conducted at 438 sites in 20 countries. The trial was designed to continue until the occurrence of at least 633 primary outcome events, as confirmed by central, blinded review by an independent event-adjudication committee.
The trial was conducted in accordance with the provisions of the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice Guidelines.11,12 The protocol (available with the full text of this article at NEJM.org) was approved by the independent ethics committee or institutional review board at each trial center. Written informed consent was obtained from each patient before any trial-related activities.
The trial was funded and conducted by Novo Nordisk. Statogen Consulting and Novo Nordisk both independently analyzed the data only after the database lock. The steering committee, which was composed of the authors, participated in designing the trial, analyzing the data, editing an earlier version of the manuscript, and making the decision to submit...