Comparison of once- versus twice-daily administration of insulin detemir, used with mealtime insulin aspart, in basal-bolus therapy for type 1 diabetes: assessment of detemir administration in a progressive treat-to-target trial (ADAPT)

Abstract

Objective: The purpose of this study was to compare effects of insulin detemir once daily versus twice a day in a basal-bolus insulin regimen.

Research design and methods: In this open-label, 7-month study, 520 patients with type 1 diabetes were randomly assigned to receive detemir once daily or twice daily with mealtime insulin aspart. Insulin doses were titrated over 1 month, with patients followed up over the subsequent 3 months. Thereafter, patients were able to switch from one regimen to the other, with an additional nonrandomized 3-month follow-up, to a total of 7 months. The primary end point was A1C at 4 months, with noninferiority defined as a difference <0.4% between groups.

Results: A1C at 4 months was 8.1 +/- 0.9 versus 8.0 +/- 1.0% with once- and twice-daily detemir, respectively, with an adjusted between-group difference of 0.12% (95% CI -0.01 to 0.25%), showing noninferiority for once-daily dosing. Similar results were found in the per protocol population. Improvement in A1C was similar in both groups (-0.4 +/- 0.8 vs. -0.5 +/- 0.8%; P = 0.09, NS) but with differences in the 7-point glucose profile. Detemir doses were lower (29 +/- 18 vs. 39 +/- 20 units/day, P < 0.001), but aspart doses were higher (34 +/- 17 vs. 26 +/- 14 IU/day, P < 0.001) with once-daily detemir. At 7 months, A1C decreased slightly in patients switched from once-daily to twice-daily administration (8.2 +/- 0.8 vs. 8.0 +/- 0.8%; P = 0.34, NS) in association with increased total insulin doses (P < 0.05), but A1C increased in those switched from twice-daily to once-daily administration (7.2 +/- 0.9 vs. 7.6 +/- 0.8%, P < 0.05) in association with decreased doses (P < 0.05).

Conclusions: Although some individuals may benefit from twice-daily dosing, the most suitable routine starting schedule for detemir in a basal-bolus regimen for type 1 diabetes is once-daily injection.

Trial registration: ClinicalTrials.gov NCT00117780.

Figure 1

A: A1C values at baseline and at 4 and 7 months according to the original randomization group. •, patients originally randomized to once-daily detemir; ▪, patients originally randomized to twice-daily detemir. B: A1C values at baseline and at 4 and 7 months according to the original and final basal dosing frequency. Error bars show SD. ○, patients staying on once-daily detemir after 4 months; •, patients switching from once- to twice-daily detemir at 4 months; □, patients staying on twice-daily detemir after 4 months; ▪, patients switching from twice- to once-daily detemir at 4 months.

Figure 2

Capillary glucose profiles at 4 months in once-daily (OD) and twice-daily (BID) detemir groups. Mean glucose levels are shown, with error bars representing SD.

Figure 3

Detemir and aspart doses after 4 and 7 months in four groups of patients. Significant changes of total insulin doses (4 vs. 7 months; P < 0.05) were observed for patients switching from once-daily (OD) to twice-daily (BID) and from twice daily to once-daily detemir. Significance represents the change in total insulin dose. □, total aspart; , detemir at breakfast; ▪, detemir at bedtime. d, day.