Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes

Year: 2017

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: BACKGROUND: Degludec is an ultralong-acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-to-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec. METHODS: We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-to-target, event-driven cardiovascular outcomes trial. The primary composite outcome in the time-to-event analysis was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) with a prespecified noninferiority margin of 1.3. Adjudicated severe hypoglycemia, as defined by the American Diabetes Association, was the prespecified, multiplicity-adjusted secondary outcome. RESULTS: Of the patients who underwent randomization, 6509 (85.2%) had established cardiovascular disease, chronic kidney disease, or both. At baseline, the mean age was 65.0 years, the mean duration of diabetes was 16.4 years, and the mean (±SD) glycated hemoglobin level was 8.4±1.7%; 83.9% of the patients were receiving insulin. The primary outcome occurred in 325 patients (8.5%) in the degludec group and in 356 (9.3%) in the glargine group (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P<0.001 for noninferiority). At 24 months, the mean glycated hemoglobin level was 7.5±1.2% in each group, whereas the mean fasting plasma glucose level was significantly lower in the degludec group than in the glargine group (128±56 vs. 136±57 mg per deciliter, P<0.001). Prespecified adjudicated severe hypoglycemia occurred in 187 patients (4.9%) in the degludec group and in 252 (6.6%) in the glargine group, for an absolute difference of 1.7 percentage points (rate ratio, 0.60; P<0.001 for superiority; odds ratio, 0.73; P<0.001 for superiority). Rates of adverse events did not differ between the two groups. CONCLUSIONS: Among patients with type 2 diabetes at high risk for cardiovascular events, degludec was noninferior to glargine with respect to the incidence of major cardiovascular events. (Funded by Novo Nordisk and others; DEVOTE ClinicalTrials.gov number, NCT01959529 .).

Source: New England Journal of Medicine

DOI: 10.1056/nejmoa1615692

Authors: Steven P. Marso, Darren K. McGuire, Bernard Zinman, Neil R. Poulter, Scott S. Emerson, Thomas R. Pieber, Richard E. Pratley, Poul-Martin Haahr, Martin Lange, Kirstine Brown-Frandsen, Alan Moses, Simon Skibsted, Kajsa Kvist, John B. Buse

Institutions: Mount Sinai Hospital, University of Toronto, University of Washington, Medical University of Graz, Lunenfeld-Tanenbaum Research Institute, Research Medical Center, Imperial College London, The University of Texas Southwestern Medical Center, Sanford Burnham Prebys Medical Discovery Institute, Translational Research Institute for Metabolism and Diabetes, AdventHealth, Novo Nordisk (Denmark), University of North Carolina at Chapel Hill

Language: English

Topic: Diabetes Treatment and Management

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Awards: G1507197878, NIHR Senior Investigator Award, North Carolina Translational & Clinical Sciences Institute (NC TraCS), NIHR Senior Investigator Award, G6322196024, North Carolina Translational and Clinical Science Institute (NC TraCS), G8903934815, Short-Term Institutional Research Training Grant, NYR-Diabetes Research Center (NYR-DRC)

OpenAlex ID: W2625031949