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

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

Sponsors

Lead sponsor: Marcus Borchert

Collaborator: ikfe-CRO GmbH
Boehringer Ingelheim

Source ikfe-CRO GmbH
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.

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.

Overall Status Unknown status
Start Date April 2012
Completion Date October 2012
Primary Completion Date October 2012
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
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
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
Postprandial Proinsulin/Insulin Ratio after 12 weeks treatment
Postprandial Proinsulin/Insulin Ratio after 12 weeks treatment
Fasting intact Proinsulin levels after 12 weeks treatment
Fasting intact Proinsulin levels after 12 weeks treatment
Fasting Proinsulin/Insulin Ratio after 12 weeks treatment
Fasting Proinsulin/Insulin Ratio after 12 weeks treatment
Fasting Blood Glucose after 12 weeks treatment
Fasting Blood Glucose after 12 weeks treatment
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
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
Fasting Lipids after 12 weeks treatment
Fasting Lipids after 12 weeks treatment
Postprandial Lipids after 12 weeks treatment
Postprandial Lipids after 12 weeks treatment
Fasting Erythrocyte Flexibility after 12 weeks treatment
Fasting Erythrocyte Flexibility after 12 weeks treatment
Postprandial Erythrocyte Flexibility after 12 weeks treatment
Postprandial Erythrocyte Flexibility after 12 weeks treatment
Fasting GLP-1 levels after 12 weeks treatment
Fasting GLP-1 levels after 12 weeks treatment
Postprandial GLP-1 levels after 12 weeks treatment
Postprandial GLP-1 levels after 12 weeks treatment
Fasting cGMP after 12 weeks treatment
Fasting cGMP after 12 weeks treatment
Postprandial cGMP after 12 weeks treatment
Postprandial cGMP after 12 weeks treatment
Fasting Calcitonin after 12 weeks treatment
Fasting Calcitonin after 12 weeks treatment
Fasting PAI-1 levels after 12 weeks treatment
Fasting PAI-1 levels after 12 weeks treatment
Postprandial PAI-1 levels after 12 weeks treatment
Postprandial PAI-1 levels after 12 weeks treatment
Fasting ADMA levels after 12 weeks treatment
Fasting ADMA levels after 12 weeks treatment
Postprandial ADMA levels after 12 weeks treatment
Postprandial ADMA levels after 12 weeks treatment
Fasting Malonyldialdehyd after 12 weeks treatment
Fasting Malonyldialdehyd after 12 weeks treatment
fasting oxidatively modified nucleosides 8-oxodG and 8-oxoGuo after 12 weeks treatment
fasting oxidatively modified nucleosides 8-oxodG and 8-oxoGuo after 12 weeks treatment
Secondary Outcome
Measure Time Frame
Hypoglycemic events after 12 weeks treatment
Body Weight after 12 weeks treatment
Enrollment 40
Condition
Intervention

Intervention type: Drug

Intervention name: Linagliptin

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

Arm group label: Trajenta

Intervention type: Drug

Intervention name: Glimepiride

Description: Glimepiride 1-4mg (individually dosed) as add on therapy to an existing metformin therapy

Arm group label: Glimepiride-ratiopharm

Other name: Glimepirid-ratiopharm

Eligibility

Criteria:

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)

Gender: All

Minimum age: 45 Years

Maximum age: 75 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Thomas Forst, MD, PhD Principal Investigator Ikfe GmbH
Overall Contact

Last name: Thomas Forst, MD, PhD

Phone: + 49 6131 57636

Phone ext: 16

Email: [email protected]

Location
facility status contact contact_backup investigator
ikfe GmbH Recruiting Thomas Forst, MD, PhD + 49 6131 57636 16 [email protected] Daniela Sachsenheimer, MD Sub-Investigator Stephanie Helleberg, MD Sub-Investigator Stefan Diessel Sub-Investigator Michael Mitry, MD Sub-Investigator
Location Countries

Germany

Verification Date

April 2012

Responsible Party

Responsible party type: Sponsor-Investigator

Investigator affiliation: ikfe-CRO GmbH

Investigator full name: Marcus Borchert

Investigator title: Prof. Dr. Thomas Forst

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Glimepiride-ratiopharm

Arm group type: Active Comparator

Description: Glimepiride (1-4mg) as add on therapy

Arm group label: Trajenta

Arm group type: Experimental

Description: Linagliptin 5 mg as add on therapy

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Basic Science

Masking: None (Open Label)

Source: ClinicalTrials.gov