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Effect of Linagliptin in Comparison With Glimepiride as Add on to Metformin on Postprandial Beta Cell Function, Postprandial Metabolism and Oxidative Stress in Patients With Type 2 Diabetes Mellitus

Sponsor
Marcus Borchert (Industry)
Overall Status
Unknown status
CT.gov ID
NCT01547104
Collaborator
ikfe-CRO GmbH (Industry), Boehringer Ingelheim (Industry)
40
Enrollment
1
Location
2
Arms
6
Duration (Months)
6.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this mechanistic study is to investigate the effect of Linagliptin in comparison to Glimepiride as add on therapy on several parameters characterizing postprandial metabolism and oxidative stress in type 2 diabetic patients on stable control with metformin.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

The goal of this mechanistic study is to investigate the effect of Linagliptin in comparison to Glimepiride as add on therapy on several parameters characterizing postprandial metabolism and oxidative stress in type 2 diabetic patients on stable control with metformin.

This mechanistic phase IV study has a prospective, comparative, open, randomized, two arm and exploratory design. Overall 40 Patients will be randomized to two treatment arms both receiving Metformin at a maximally tolerated dose. In addition to that both treatment groups will receive either an individually titrated dose of Glimepiride or 5mg once daily of Linagliptin. Subsequent to a standardized meal, several parameters reflecting beta cell function, metabolism and oxidative stress will be evaluated.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
40 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Effect of Linagliptin in Comparison With Glimepiride as Add on to Metformin on Postprandial Beta Cell Function, Postprandial Metabolism and Oxidative Stress in Patients With Type 2 Diabetes Mellitus
Study Start Date :
Apr 1, 2012
Anticipated Primary Completion Date :
Oct 1, 2012
Anticipated Study Completion Date :
Oct 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Glimepiride-ratiopharm

Glimepiride (1-4mg) as add on therapy

Drug: Glimepiride
Glimepiride 1-4mg (individually dosed) as add on therapy to an existing metformin therapy
Other Names:
  • Glimepirid-ratiopharm

    		•
    Experimental: Trajenta

    Linagliptin 5 mg as add on therapy

    Drug: Linagliptin
    Linagliptin dosed 5 mg as add on therapy to an existing metformin therapy

    Outcome Measures

    Primary Outcome Measures

    1. Postprandial increase in intact Proinsulin levels (Peak, AUC) [30, 60, 90, 120, 150, 180, 210, 240, 270 300 mins post test meal procedure, 3 times within 12 weeks treatment]

    2. Postprandial Proinsulin/Insulin Ratio [after 12 weeks treatment]

    3. Fasting intact Proinsulin levels [after 12 weeks treatment]

    4. Fasting Proinsulin/Insulin Ratio [after 12 weeks treatment]

    5. Fasting Blood Glucose [after 12 weeks treatment]

    6. Postprandial Blood Glucose Excursions (Peak; AUC) [30, 60, 90, 120, 150, 180, 210, 240, 270 300 mins post test meal procedure, 3 times within 12 weeks treatment]

    7. Fasting Lipids [after 12 weeks treatment]

    8. Postprandial Lipids [after 12 weeks treatment]

    9. Fasting Erythrocyte Flexibility [after 12 weeks treatment]

    10. Postprandial Erythrocyte Flexibility [after 12 weeks treatment]

    11. Fasting GLP-1 levels [after 12 weeks treatment]

    12. Postprandial GLP-1 levels [after 12 weeks treatment]

    13. Fasting cGMP [after 12 weeks treatment]

    14. Postprandial cGMP [after 12 weeks treatment]

    15. Fasting Calcitonin [after 12 weeks treatment]

    16. Fasting PAI-1 levels [after 12 weeks treatment]

    17. Postprandial PAI-1 levels [after 12 weeks treatment]

    18. Fasting ADMA levels [after 12 weeks treatment]

    19. Postprandial ADMA levels [after 12 weeks treatment]

    20. Fasting Malonyldialdehyd [after 12 weeks treatment]

    21. fasting oxidatively modified nucleosides 8-oxodG and 8-oxoGuo [after 12 weeks treatment]

    Secondary Outcome Measures

    1. Hypoglycemic events [after 12 weeks treatment]

    2. Body Weight [after 12 weeks treatment]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    45 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Diabetes mellitus type 2

    2. HbA1c > 6.5% - ≤ 8.5%

    3. HbA1c > 7.0% - ≤ 8.5% for those patients with a significant cardiovascular history

    4. Treatment with metformin at a maximum tolerated dose

    5. Age 45 - 75 years (inclusively)

    6. Patient consents that his/her family physician/diabetologist will be informed of trial participation.

    Exclusion Criteria:

    1. Pretreatment with PPAR gamma agonists within the last three months

    2. History of type 1 diabetes

    3. Uncontrolled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >90 mmHg)

    4. Acute infections

    5. Medical history of hypersensitivity to the study drugs or to drugs with similar chemical structures

    6. History of severe or multiple allergies

    7. Treatment with any other investigational drug within 3 months before trial entry.

    8. Progressive fatal disease

    9. History of drug or alcohol abuse in the past 2 years

    10. State after kidney transplantation

    11. Serum potassium > 5.5 mmol/L

    12. Pregnancy or breast feeding

    13. Sexually active woman of childbearing age not practicing a highly effective method of birth control as defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs, sexual abstinence or vasectomized partner.

    14. Acute myocardial infarction, open heart surgery or cerebral event (stroke/TIA) within the previous 30 days

    15. Any elective surgery during study participation

    16. Have had more than one unexplained episode of severe hypoglycemia (defined as requiring assistance of another person due to disabling hypoglycemia) within 6 months prior to screening visit

    17. History of pancreatitis

    18. History of dehydration, pre-coma diabeticum or diabetic ketoacidosis

    19. Acute or scheduled investigation with iodine containing radiopaque material

    20. Uncontrolled unstable angina pectoris

    21. History of pericarditis, myocarditis, endocarditis

    22. Recent pulmonary embolism

    23. Hemodynamic relevant aortic stenosis

    24. Aortic aneurysm

    25. Regular use of NSAID's (no acute use of NSAID within 48 hours before V2,V4,V5)

    26. Lack of compliance or other similar reason that, according to investigator, precludes satisfactory participation in the study

    27. History of respiratory, gastrointestinal, hepatic (ALAT and/or ASAT > 3 times the normal reference range), renal (Creatinine > 1.1 mg/dl in women and > 1.5 mg/dl in men ), neurological, psychiatric and/or hematological disease as judged by the investigator

    28. Lactose intolerance

    29. Intake of Coumarin or coumarin derived compounds such as phenprocoumon (Marcumar) or warfarin (Coumadin, Warfant)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 ikfe GmbH Mainz Rhineland-Palatinate Germany 55116

    Sponsors and Collaborators

    • Marcus Borchert
    • ikfe-CRO GmbH
    • Boehringer Ingelheim

    Investigators

    • Principal Investigator: Thomas Forst, MD, PhD, Ikfe GmbH

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Marcus Borchert, Prof. Dr. Thomas Forst, ikfe-CRO GmbH
    ClinicalTrials.gov Identifier:
    NCT01547104
    Other Study ID Numbers:
    • ikfe-Lina-002
    • 2012-000179-17
    First Posted:
    Mar 7, 2012
    Last Update Posted:
    Apr 11, 2012
    Last Verified:
    Apr 1, 2012
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Glimepiride
    Linagliptin

    Study Results

    No Results Posted as of Apr 11, 2012