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

Diabetes Mellitus Type 2 Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01547104
• Other study ID #: ikfe-Lina-002
• Secondary ID: 2012-000179-17
• Status: Recruiting
• Phase: Phase 4
• First received: February 21, 2012
• Last updated: April 10, 2012
• Start date: April 2012
• Est. completion date: October 2012

Study information

• Verified date: April 2012
• Source: ikfe-CRO GmbH
• Contact: Thomas Forst, MD, PhD
• Phone: + 49 6131 57636
• Email: ThomasF[@]ikfe.de
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 75 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus Type 2
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Linagliptin
Linagliptin dosed 5 mg as add on therapy to an existing metformin therapy
• Glimepiride
Glimepiride 1-4mg (individually dosed) as add on therapy to an existing metformin therapy

Locations

Country	Name	City	State
Germany	ikfe GmbH	Mainz	Rhineland-Palatinate

Sponsors (3)

Lead Sponsor	Collaborator
Marcus Borchert	Boehringer Ingelheim, ikfe-CRO GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Postprandial Proinsulin/Insulin Ratio		after 12 weeks treatment	No
Primary	Fasting intact Proinsulin levels		after 12 weeks treatment	No
Primary	Fasting Proinsulin/Insulin Ratio		after 12 weeks treatment	No
Primary	Fasting Blood Glucose		after 12 weeks treatment	No
Primary	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	No
Primary	Fasting Lipids		after 12 weeks treatment	No
Primary	Postprandial Lipids		after 12 weeks treatment	No
Primary	Fasting Erythrocyte Flexibility		after 12 weeks treatment	No
Primary	Postprandial Erythrocyte Flexibility		after 12 weeks treatment	No
Primary	Fasting GLP-1 levels		after 12 weeks treatment	No
Primary	Postprandial GLP-1 levels		after 12 weeks treatment	No
Primary	Fasting cGMP		after 12 weeks treatment	No
Primary	Postprandial cGMP		after 12 weeks treatment	No
Primary	Fasting Calcitonin		after 12 weeks treatment	No
Primary	Fasting PAI-1 levels		after 12 weeks treatment	No
Primary	Postprandial PAI-1 levels		after 12 weeks treatment	No
Primary	Fasting ADMA levels		after 12 weeks treatment	No
Primary	Postprandial ADMA levels		after 12 weeks treatment	No
Primary	Fasting Malonyldialdehyd		after 12 weeks treatment	No
Primary	fasting oxidatively modified nucleosides 8-oxodG and 8-oxoGuo		after 12 weeks treatment	No
Secondary	Hypoglycemic events		after 12 weeks treatment	Yes
Secondary	Body Weight		after 12 weeks treatment	Yes