Linagliptin in Combination With Metformin in Treatment Naive Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: metformin placebo; linagliptin placebo; metformin; metformin; linagliptin
Intervention description: metformin placebo tablets 500mg; linagliptin placebo tablets 5mg; metformin tablets 500mg; metformin tablets 500 mg; linagliptin tablets 5mg
Intervention MeSH terms: Metformin; Linagliptin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 689.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The aim of this study is to investigate the impact of the combination therapy of linagliptin
      and metformin at submaximal doses in reduction of Glycosylated haemoglobin (HbA1c) and
      metformin pre-specified gastro-intestinal (GI) side effects in treatment naive patients of
      with type 2 diabetes mellitus.
    

Eligibility criteria:

        Inclusion criteria:

          1. Diagnosis of Type 2 diabetes mellitus (T2DM) prior to informed consent;

          2. Male and female patients on diet and exercise regimen who are drug naive, defined as
             absence of any oral antidiabetic therapy or insulin for 12 weeks prior to
             randomization

          3. Glycosylated haemoglobin A1c (HbA1c) >/= 7.0% (53 mmol/mol) to </= 10.0% (86 mmol/mol)
             at visit 1 (screening);

          4. Age>/=18 and </=80 years at visit 1(screening);

          5. Body Mass Index (BMI)</= 45kg/m2 at visit 1 (screening);

          6. Signed and dated written informed consent by date of visit 1 in accordance with Good
             Clinical Practice (GCP) and local legislation

        Exclusion criteria:

          1. Uncontrolled hyperglycaemia with a glucose level >240 mg/dl (13.3mmol/L) after an
             overnight fast during screening/placebo run-in and confirmed by a second measurement
             (Not on the same day);

          2. Treatment with any oral antidiabetic drug or insulin within 12 weeks prior to
             randomization

          3. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris),stroke or
             Transient ischemia attack (TIA) within 3 months prior to informed consent;

          4. Indication of liver disease/Impaired hepatic function, defined by serum levels of
             either Aspartate aminotransferase (ALT or SGPT), alanine aminotransferase (AST or
             SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at
             visit 1 and/or run-in phase,

          5. Impaired renal function, defined as eGFR< 60ml/min (moderate or severe renal
             impairment, modification of diet in renal disease (MDRD) formula) as determined during
             screening or at run-in phase

          6. Bariatric surgery within the past two years and other gastrointestinal surgeries that
             induced chronic malabsorption

          7. Medical history of Cancer (except for basal cell carcinoma) and/or treatment for
             cancer within the last 5 years

          8. Blood dyscrasia or any other disorders causing haemolysis or unstable Red Blood Cell
             (eg. malaria, babesiosis, haemolytic anemia)

          9. Known history of pancreatitis and chronic pancreatitis

         10. Contraindications to metformin according to the local label

         11. Treatment with anti-obesity drugs 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

         12. 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 T2DM

         13. Pre-menopausal women (last menstruation less than 1 year prior to informed consent)
             who:

               1. are nursing or pregnant or

               2. 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 study
                  and do not agree to submit to periodic pregnancy testing during participation in
                  the trial or who do not agree to continue contraception for at least 30 days
                  after the last dose of study drug. Acceptable methods of birth control include
                  tubal ligation, transdermal patch, intra-uterine devices/systems(IUDs/IUSs),
                  oral, implantable, or injectable contraceptives, complete sexual abstinence (if
                  acceptable by local authorities), double barrier method and vasectomized partner.

         14. Alcohol or drug abuse within 3 months prior to informed consent that would interfere
             with trial participation or any ongoing condition leading to a decreased compliance to
             study procedures or study drug intake

         15. Participation in another trial with application of any investigational drug within 30
             days prior to informed consent

         16. Any other clinical condition that would jeopardize patients safety while participating
             in this trial