The effect of insulin degludec in combination with liraglutide and metformin in subjects with type 2 diabetes qualifying for treatment intensification. NN1250-3944
This is a 26-week, randomised (1:1), parallel, double-blind, multi-national, controlled trial comparing efficacy and safety of IDeg to placebo, both in combination with liraglutide and metformin in subjects with type 2 diabetes mellitus qualifying for treatment intensification.
Total trial duration for the individual subjects will be up to 44 weeks. The trial includes a screening visit (Visit 1), a 15-week run-in period, followed by frequent visits during the 26-week randomised treatment period and a follow-up visit at least 7 days after the actual date of the last treatment visit.
After the 15-week run-in, eligible subjects will be randomised and enter a 26-week treatment period with IDeg/placebo, which is expected to be sufficient to optimise the trial treatment regimen and to obtain data for efficacy and safety evaluation.
The two-arm parallel trial design has been chosen instead of a cross-over design in order to avoid a carry-over effect. The add-on design has been chosen to isolate the effect of adding IDeg to liraglutide. Placebo is used as comparator to ensure a reference group for scientifically valid evaluation of efficacy and safety of IDeg intervention together with liraglutide and metformin, thus reflecting the progressive nature of T2DM and the requirement for multiple drug therapy. The randomised treatment is double-blinded in order to minimize bias from subjects and investigator. The primary endpoint HbA1c is a laboratory parameter and consequently the probability of assessment bias is limited. The multinational approach is to ensure that the results are applicable for subjects with different demographic characteristics.
1. Informed consent obtained before any trial-related activities. Trial-related activities are any
procedures that would not have been performed during normal management of the subject.
2. ≥ 18 years of age
3. Type 2 diabetes (diagnosed clinically) for ≥ 24 weeks prior to Visit 1
4. Insulin naïve. Allowed are previous short term insulin treatment < or = to 14 days in total. Treatment during hospitalisation or during gestational diabetes is allowed for periods >14 days in total
5. Ongoing treatment with metformin or metformin in combination with either sulphonylurea (SU)
or glinides or dipeptidyl peptidase-IV (DPP-IV) inhibitors or exenatide (only BID) with the
following minimum doses unchanged for ≥ 12 weeks prior to Visit 1:
Metformin: ≥ 1500 mg daily or maximum tolerated dose
SU or glinide: minimum half of the maximum dose according to local labelling
DPP-IV inhibitor: minimum half of the maximum dose according to local labelling
Exenatide (only BID is allowed): minimum 10μg BID
6. HbA1c as assessed by central laboratory:
7.5-10.0% (both inclusive) for subjects on metformin monotherapy
7.0-9.0% (both inclusive) for subjects on metformin in combination with either SU, glinides,
DPP-IV inhibitors or exenatide (only BID)
7. BMI < or = to 45 kg/m2
8. Ability and willingness to adhere to the protocol including self measurement of plasma glucose
according to the protocol