Insulin Degludec/Insulin Aspart Administered Once Daily at Any Meal, With Insulin Aspart at Other Meals Versus a Standard Basal-Bolus Regimen in Patients With Type 1 Diabetes

A 26-week, phase 3, randomized, open-label, treat-to-target trial

  1. Melanie Davies, MD9
  1. 1University of Washington Medical Center-Roosevelt, Seattle, Washington
  2. 2Atlanta Diabetes Association, Atlanta, Georgia
  3. 3Diabetology and Vascular Disease Unit, General Hospital, Narbonne, France
  4. 4BioStat Degludec, Novo Nordisk A/S, Søborg, Denmark
  5. 5Department of Internal Diseases, Endocrinology, and Diabetology, CSK MSWiA, and Medical Research Center, Polish Academy of Science, Warsaw, Poland
  6. 6Department of Endocrinology and Metabolism MEA, Aarhus University Hospital, Aarhus, Denmark
  7. 7Department of Endocrinology, Diabetes Care Center, Salinas, California
  8. 8Medical and Science Degludec, Novo Nordisk A/S, Søborg, Denmark
  9. 9Department of Cardiovascular Sciences, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, U.K.
  1. Corresponding author: Irl B. Hirsch, ihirsch{at}u.washington.edu.

Abstract

OBJECTIVE To evaluate efficacy and tolerability of a co-formulation of insulin degludec and insulin aspart (IDegAsp) with insulin aspart (IAsp) at other meals compared with basal-bolus therapy using insulin detemir (IDet) and IAsp.

RESEARCH DESIGN AND METHODS Adults (n = 548) with type 1 diabetes (A1C 7.0–10.0%; BMI ≤35.0 kg/m2) were randomized 2:1 in a 26-week, multinational, parallel-group, treat-to-target trial to IDegAsp or IDet. IDegAsp was given with a meal, and IDet was given in the evening, with a second (breakfast) dose added if needed.

RESULTS Non-inferiority for IDegAsp versus IDet was confirmed; A1C improved by 0.75% with IDegAsp and 0.70% with IDet to 7.6% in both groups (estimated treatment difference IDegAsp − IDet: –0.05% [95% CI –0.18 to 0.08]). There was no statistically significant difference between IDegAsp and IDet in the rates of severe hypoglycemia (0.33 and 0.42 episodes/patient-year, respectively) or overall confirmed (plasma glucose <3.1 mmol/L) hypoglycemia (39.17 and 44.34 episodes/patient-year, respectively). Nocturnal confirmed hypoglycemia rate was 37% lower with IDegAsp than IDet (3.71 vs. 5.72 episodes/patient-year, P < 0.05). Weight gain was 2.3 and 1.3 kg with IDegAsp and IDet, respectively (P < 0.05). Total insulin dose was 13% lower in the IDegAsp group (P < 0.0001). No treatment differences were detected in Health-Related Quality of Life, laboratory measurements, physical examination, vital signs, electrocardiograms, fundoscopy, or adverse events.

CONCLUSIONS IDegAsp in basal-bolus therapy with IAsp at additional mealtimes improves overall glycemic control and was non-inferior to IDet, with a reduced risk of nocturnal hypoglycemia and fewer injections in comparison with IDet + IAsp basal-bolus therapy.

  • Received December 23, 2011.
  • Accepted May 25, 2012.

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  1. Diabetes Care
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