David Russell-Jones1, Bruce W Bode2, Christophe De Block3, Edward Franek4, Simon R Heller5, Chantal Mathieu6, Athena Philis-Tsimikas7, Ludger Rose8, Vincent C Woo9, Anne Birk Østerskov10, Tina Graungaard10, Richard M Bergenstal11. 1. Diabetes and Endocrinology, Royal Surrey County Hospital, and University of Surrey, Guildford, U.K. davidrussell-jones@nhs.net. 2. Atlanta Diabetes Associates, Atlanta, GA. 3. Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, Antwerp, Belgium. 4. Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland. 5. Department of Oncology and Metabolism, University of Sheffield, Sheffield, U.K. 6. Clinical and Experimental Endocrinology, University Hospital Leuven, Catholic University of Leuven, Leuven, Belgium. 7. Scripps Whittier Diabetes Institute, Scripps Health, San Diego, CA. 8. Institute of Diabetes Research, Münster, Germany. 9. Section of Endocrinology and Metabolism, University of Manitoba, Winnipeg, Manitoba, Canada. 10. Novo Nordisk A/S, Søborg, Denmark. 11. International Diabetes Center at Park Nicollet, Minneapolis, MN.
Abstract
OBJECTIVE: This multicenter, treat-to-target, phase 3 trial evaluated the efficacy and safety of fast-acting insulin aspart (faster aspart) versus conventional insulin aspart (IAsp) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: The primary end point was change from baseline in HbA1c after 26 weeks. After an 8-week run-in, subjects were randomized (1:1:1) to double-blind mealtime faster aspart (n = 381), IAsp (n = 380), or open-label postmeal faster aspart (n = 382)-each with insulin detemir. RESULTS:HbA1c was reduced in both treatment groups, and noninferiority to IAsp was confirmed for both mealtime and postmeal faster aspart (estimated treatment difference [ETD] faster aspart-IAsp, mealtime, -0.15% [95% CI -0.23; -0.07], and postmeal, 0.04% [-0.04; 0.12]); mealtime faster aspart statistically significantly reduced HbA1c versus IAsp (P = 0.0003). Postprandial plasma glucose (PPG) increments were statistically significantly lower with mealtime faster aspart at 1 h (ETD -1.18 mmol/L [95% CI -1.65; -0.71], -21.21 mg/dL [-29.65; -12.77]; P < 0.0001) and 2 h (-0.67 mmol/L [-1.29; -0.04], -12.01 mg/dL [-23.33; -0.70]; P = 0.0375) after the meal test; superiority to IAsp for the 2-h PPG increment was confirmed. The overall rate of severe or blood glucose-confirmed (plasma glucose <3.1 mmol/L [56 mg/dL]) hypoglycemic episodes and safety profiles were similar between treatments. CONCLUSIONS: Faster aspart effectively improved HbA1c, and noninferiority to IAsp was confirmed, with superior PPG control for mealtime faster aspart versus IAsp. Subjects randomized to postmeal faster aspart for all meals maintained HbA1c noninferior to that obtained with mealtime IAsp.
RCT Entities:
OBJECTIVE: This multicenter, treat-to-target, phase 3 trial evaluated the efficacy and safety of fast-acting insulinaspart (faster aspart) versus conventional insulinaspart (IAsp) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: The primary end point was change from baseline in HbA1c after 26 weeks. After an 8-week run-in, subjects were randomized (1:1:1) to double-blind mealtime faster aspart (n = 381), IAsp (n = 380), or open-label postmeal faster aspart (n = 382)-each with insulin detemir. RESULTS: HbA1c was reduced in both treatment groups, and noninferiority to IAsp was confirmed for both mealtime and postmeal faster aspart (estimated treatment difference [ETD] faster aspart-IAsp, mealtime, -0.15% [95% CI -0.23; -0.07], and postmeal, 0.04% [-0.04; 0.12]); mealtime faster aspart statistically significantly reduced HbA1c versus IAsp (P = 0.0003). Postprandial plasma glucose (PPG) increments were statistically significantly lower with mealtime faster aspart at 1 h (ETD -1.18 mmol/L [95% CI -1.65; -0.71], -21.21 mg/dL [-29.65; -12.77]; P < 0.0001) and 2 h (-0.67 mmol/L [-1.29; -0.04], -12.01 mg/dL [-23.33; -0.70]; P = 0.0375) after the meal test; superiority to IAsp for the 2-h PPG increment was confirmed. The overall rate of severe or blood glucose-confirmed (plasma glucose <3.1 mmol/L [56 mg/dL]) hypoglycemic episodes and safety profiles were similar between treatments. CONCLUSIONS: Faster aspart effectively improved HbA1c, and noninferiority to IAsp was confirmed, with superior PPG control for mealtime faster aspart versus IAsp. Subjects randomized to postmeal faster aspart for all meals maintained HbA1c noninferior to that obtained with mealtime IAsp.
Authors: Bruce W Bode; Violeta Iotova; Margarita Kovarenko; Lori M Laffel; Paturi V Rao; Srikanth Deenadayalan; Magnus Ekelund; Steffen Falgreen Larsen; Thomas Danne Journal: Diabetes Care Date: 2019-05-10 Impact factor: 19.112