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
- Irl B. Hirsch, MD1⇓,
- Bruce Bode, MD2,
- Jean-Pierre Courreges, MD3,
- Patrik Dykiel, MSC4,
- Edward Franek, MD5,
- Kjeld Hermansen, MD6,
- Allen King, MD7,
- Henriette Mersebach, MD8 and
- Melanie Davies, MD9
- 1University of Washington Medical Center-Roosevelt, Seattle, Washington
- 2Atlanta Diabetes Association, Atlanta, Georgia
- 3Diabetology and Vascular Disease Unit, General Hospital, Narbonne, France
- 4BioStat Degludec, Novo Nordisk A/S, Søborg, Denmark
- 5Department of Internal Diseases, Endocrinology, and Diabetology, CSK MSWiA, and Medical Research Center, Polish Academy of Science, Warsaw, Poland
- 6Department of Endocrinology and Metabolism MEA, Aarhus University Hospital, Aarhus, Denmark
- 7Department of Endocrinology, Diabetes Care Center, Salinas, California
- 8Medical and Science Degludec, Novo Nordisk A/S, Søborg, Denmark
- 9Department of Cardiovascular Sciences, University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, U.K.
- Corresponding author: Irl B. Hirsch, .
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.
- © 2012 by the American Diabetes Association.
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