Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes: A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Subjects With Type 2 Diabetes
Condition: Diabetes; Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: insulin degludec/liraglutide; insulin degludec; liraglutide
Intervention description: Insulin degludec/liraglutide treatment will be initiated and titrated (individually adjusted) twice weekly according to the mean self measured plasma glucose (SMPG) (fasting). Insulin degludec/liraglutide is injected subcutaneously (under the skin) once daily.; Insulin degludec treatment will be initiated with 10 U and titrated (individually adjusted) twice weekly according to the mean SMPG (fasting). Insulin degludec is injected subcutaneously (under the skin) once daily.; Liraglutide will be started with 0.6 mg and subsequent 0.6 mg weekly dose escalation to 1.8 mg. Liraglutide dose of 1.8 mg/day will be continued for the remaining part of the trial. Liraglutide is injected subcutaneously (under the skin) once daily.
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Liraglutide; Insulin, Long-Acting; Xultophy
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1663.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This trial is conducted globally. The aim of this trial is to compare the efficacy and safety
      of insulin degludec/liraglutide (IDegLira) versus insulin degludec (IDeg) and liraglutide
      (Lira) in subjects with type 2 diabetes. Subjects are to continue their pre-trial treatment
      with metformin or metformin + pioglitazone throughout the entire trial.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with type 2 diabetes

          -  HbA1c 7.0-10.0 % (both inclusive) with the aim of a median HbA1c of 8.3%. Accordingly,
             when approximately 50% of the randomised subjects have a HbA1c above 8.3%, the
             remaining subjects randomised must have a HbA1c of below or equal to 8.3%, or when
             approximately 50% of the randomised subjects have a HbA1c of below or equal to 8.3%,
             the remaining subjects randomised must have a HbA1c above 8.3%

          -  Male or female, age 18 years or above (Taiwan: 20 years or above for a site 653 in
             Taiwan: Taichung Veterans General Hospital)

          -  Subjects on stable dose of 1-2 OADs (metformin [at least 1500 mg or max tolerated
             dose] or metformin [at least 1500 mg or max tolerated dose] + pioglitazone [at least
             30 mg]) for at least 90 days prior to screening

          -  Body Mass Index (BMI) maximum 40 kg/m^2

        Exclusion Criteria:

          -  Treatment with insulin (except for short-term treatment due to intercurrent illness at
             the discretion of the Investigator)

          -  Treatment with GLP-1 (glucagon-like peptide-1) receptor agonists (eg exenatide,
             liraglutide), sulphonylurea or dipeptidyl peptidase 4 (DPP-4) inhibitors within 90
             days prior to trial

          -  Impaired liver function, defined as alanine aminotransferese (ALAT) at least 2.5 times
             Upper Normal Range (UNR) (one retest analysed at the central laboratory within a week
             from first sample taken is permitted with the result of the last sample being the
             conclusive)

          -  Impaired renal function defined as serum-creatinine at least 133 mcmol/l (at least 1.5
             mg/dl) for males and at least 125 mcmol/l (at least 1.4) for females, or as allowed
             according to local contraindications for metformin (one retest analysed at the central
             laboratory within a week from first sample taken is permitted with the result of the
             last sample being the conclusive)

          -  Screening calcitonin at least 50 ng/L

          -  Subjects with personal or family history of medullary thyroid carcinoma (MTC) or
             multiple endocrine neoplasia type 2 (MEN 2)

          -  Cardiac disorder defined as: congestive heart failure (NYHA class III-IV), diagnosis
             of unstable angina pectoris, cerebral stroke and/or myocardial infarction within the
             last 12 months and planned coronary, carotid or peripheral artery revascularisation
             procedures

          -  Severe uncontrolled treated or untreated hypertension (systolic blood pressure at
             least 180 mm Hg or diastolic blood pressure at least 100 mm Hg)

          -  Acute treatment required proliferative retinopathy or maculopathy (macular oedema)

          -  History of chronic pancreatitis or idiopathic acute pancreatitis