Linagliptin and Metformin Versus Linagliptin in Newly Diagnosed, Untreated Type 2 Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: metformin; linagliptin; metformin placebo; metformin placebo
Intervention description: 1000 mg to 2000 mg per day; 5 mg daily; 0 to 2 tablets daily; 4 tablets daily
Intervention MeSH terms: Metformin; Linagliptin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 316.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this trial is to determine whether a initial combination of linagliptin and
      metformin compared to linagliptin alone for 24 weeks is effective in newly diagnosed,
      treatment-naïve patients with Type 2 Diabetes.
    

Eligibility criteria:

        Inclusion criteria:

          1. Patients must sign and date an Informed Consent consistent with International
             Conference on Harmonisation / Good Clinical Practice guidelines and local regulations
             prior to any evaluation and participation in the trial.

          2. Male and female patients, 18 years of age or older at Visit 1 (Screen), with newly
             diagnosed (less than 12 months prior to Screen) Type 2 Diabetes Mellitus.

          3. Patients who are treatment-naïve, defined as absence of any oral antidiabetic therapy,
             injectable glucagon-like peptide-1 agonist/analogue, or insulin, and uncontrolled for
             the 12 weeks prior to randomisation.

          4. Patients must have an glycated (or glycosylated) haemoglobin (HbA1c) between 8.5% [69
             millimoles per mole (mmol/mol)] and 12.0% (108 mmol/mol) at Visit 1 (Screen).

          5. Patients must have a Body Mass Index (BMI) of 45 kg/m2 or less at Visit 1 (Screen).

          6. In the investigators opinion, patients must be reliable, honest, compliant, and agree
             to cooperate with all planned future trial evaluations as explained in detail during
             the informed consent process and to be able to perform them.

        Exclusion criteria:

        Patients with, who are, who have, or who have had:

          1. Acute coronary syndrome (non-ST Elevation Myocardial Infarction (STEMI), STEMI, and
             unstable angina pectoris), stroke or transient ischemic attack within 3 months prior
             to informed consent.

          2. Indication of liver disease determined during Screen and/or Run-In Period, defined by
             a serum level above 3 times the upper limit of normal (ULN) in any of the following:
             alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase.
             Gilbert-Meulengracht syndrome (also known as conjugated hyperbilirubinemia,
             constitutional hepatic dysfunction, or familial nonhemolytic jaundice) will be
             permitted.

          3. Impaired renal function, defined as calculated creatinine clearance of less than 60
             milliliters per minute (< 60 mL/min), by the Cockcroft-Gault Equation, as determined
             during Screen and/or Run-In Period.

          4. Bariatric, gastric bypass, and other gastrointestinal surgeries (including all types
             of gastric banding and/or LapBand) within the past two years.

          5. Medical history of cancer (except for basal cell carcinoma) and/or treatment for
             cancer within the last 5 years.

          6. Medical history of pancreatitis.

          7. Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells (e.g.,
             malaria, babesiosis, haemolytic anaemia).

          8. Any contraindication to metformin and/or linagliptin therapies, according to local
             labels.

          9. Treatment with anti-obesity drugs, including over-the-counter drugs such as Alli
             (orlistat), 3 months prior to informed consent or any other treatment at the time of
             screening (i.e., surgery, aggressive diet regimen, etc.) leading to unstable body
             weight.

         10. Current treatment with systemic steroids at time of informed consent or change in
             dosage of thyroid hormones within 6 weeks prior to informed consent or any other
             uncontrolled endocrine disorder except Type 2 Diabetes Mellitus.

         11. Pre-menopausal women (last menstruation of 1 year or less prior to informed consent)
             who are nursing or pregnant, are of child-bearing potential and are not practicing an
             acceptable method of birth control, or do not plan to continue using this method
             throughout the trial and do not agree to submit to periodic pregnancy testing during
             participation in the trial.

             Note: Acceptable methods of birth control include tubal ligation, transdermal patch,
             intra uterine devices/systems, oral, implantable, intra-vaginal, or injectable
             contraceptives, Essure micro-inserts placed more than six months prior to Screen
             Visit, complete sexual abstinence (if acceptable by local authorities), double barrier
             method (e.g., diaphragm or condom and spermicide), and vasectomised partner.

         12. Alcohol or drug abuse within the 3 months prior to informed consent that would
             interfere with trial participation or any ongoing condition leading to decreased
             compliance to trial procedures or study medication intake in the opinion of the
             investigator.

         13. Participation in another trial with an investigational drug within 2 months prior to
             informed consent.

         14. Any other clinical condition that would jeopardize patient safety while participating
             in this clinical trial in the opinion of the Investigator.

         15. Inability to commit to regular overnight fasting of at least 10 hours duration and
             attendance to study site visits between 07:00 and 11:00 ante meridiem (a.m.).