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

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/m(2)) 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.

Trial registration: ClinicalTrials.gov NCT00978627.

Figure 1

Patient disposition during the trial.

Figure 2

Glycemic control by treatment group over time: A1C (A), FPG (B), and self-measured 9-point glucose profiles (C). *P < 0.05, between-treatment difference. BF, breakfast; FAS, full analysis set.

Figure 3

Cumulative incidence of confirmed (PG <3.1 mmol/L [56 mg/dL]) hypoglycemic episodes by treatment group during the trial: all episodes (A) and nocturnal episodes (B). SAS, safety analysis set.