Trial to Assess the Influence of 4 Weeks' Treatment With Linagliptin as Compared to Glimepiride and Placebo on Endothelial Function in Patients With Type 2 Diabetes Using FMD (Flow-Mediated Vasodilation)
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Placebo; Linagliptin; Placebo; Placebo; Placebo; Glimepiride
Intervention description: Placebo matching Glimepiride; given once daily for 28 days; Placebo matching Linagliptin; Placebo matching Linagliptin; Placebo matching Glimepiride; 1 mg for 7 days followed by uptitration to 2 mg (given for following 21 days)
Intervention MeSH terms: Glimepiride; Linagliptin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The general aim of the present study is to investigate the impact of 4 weeks treatment with
      linagliptin (5 mg) on endothelial function in patients with type 2 diabetes mellitus. In the
      current trial this effect of linagliptin treatment on endothelial function will be compared
      against both the sulfonylurea glimepiride and against placebo, which has not been tested in a
      trial before; as also is the case for other DPP-4 inhibitors.

      Besides placebo, glimepiride was chosen as a comparator, as it is one compound of the second
      most used oral antidiabetic drug class.
    

Eligibility criteria:

        Inclusion criteria:

          1. Type 2 diabetic male and female patients according to the following criteria:

             Based upon a complete medical history and clinical laboratory tests

          2. Age >= 18 and Age <= 65 years

          3. Body mass index >= 25 <= 35 kg/m2

          4. HbA1c <= 7.5%

          5. Treatment with metformin (=1500 mg daily) for <= 3 months

          6. Signed and dated written informed consent prior to admission to the study in
             accordance with GCP and the local legislation.

             For female patients of childbearing potential:

          7. Use of acceptable method of contraception (Pearl-Index <1).

        Exclusion criteria:

          1. Treatment with any glucose-lowering drug except for metformin within prior 3 months.

          2. Any finding of the medical examination (including blood pressure, pulse rate and
             electrocardiogram) deviating from normal and of clinical relevance.

          3. Any evidence of a clinically relevant acute concomitant disease

          4. History of cardiovascular disease (e.g. coronary artery disease history of acute
             myocard infarction or stroke, peripheral vascular disease).

          5. History of major diabetic complications (e.g. nephropathy, retinopathy)

          6. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, immunological or
             hormonal disorders (except: hypertension treated with angiotensin receptor blocker or
             angiotensin-converting-enzyme inhibitors, hyperlipidemia with statin therapy, thyroid
             hormone replacement therapy, all stable for at least three months prior to screening).

          7. Surgery of the gastrointestinal tract (except appendectomy).

          8. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or
             neurological disorders.

          9. History of relevant orthostatic hypotension, fainting spells or blackouts.

         10. Chronic or relevant acute infections.

         11. History of relevant allergy/hypersensitivity (including allergy to drug or its
             excipients).

         12. Intake of drugs with a long half-life (> 24 hours) within at least one month or less
             than 10 half-lives of the respective drug prior to administration or during the trial.

         13. Participation in another trial with an investigational drug within one month prior to
             administration or during the trial.

         14. Smoker (>= 1 cigarettes or >= 1 cigars or >= 1 pipes/day).

         15. Alcohol abuse (more than 60 g/day).

         16. Drug abuse.

         17. Blood donation (more than 100 mL within four weeks prior to administration or during
             the trial).

         18. Excessive physical activities (within one week prior to administration or during the
             trial).

         19. Any laboratory value outside the reference range that is of clinical relevance.