Clinical trial NCT01547104: 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
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Diabetes Mellitus Type 2
Lead sponsor: ikfe-CRO GmbH
Sponsor class: INDUSTRY
Collaborators: name: ikfe-CRO GmbH
name: Boehringer Ingelheim
First posted: 2012-03-07
Enrollment: 40
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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)

Primary outcomes:
measure: Postprandial increase in intact Proinsulin levels (Peak, AUC)
timeFrame: 30, 60, 90, 120, 150, 180, 210, 240, 270 300 mins post test meal procedure, 3 times within 12 weeks treatment
measure: Postprandial Proinsulin/Insulin Ratio
timeFrame: after 12 weeks treatment
measure: Fasting intact Proinsulin levels
timeFrame: after 12 weeks treatment
measure: Fasting Proinsulin/Insulin Ratio
timeFrame: after 12 weeks treatment
measure: Fasting Blood Glucose
timeFrame: after 12 weeks treatment
measure: Postprandial Blood Glucose Excursions (Peak; AUC)
timeFrame: 30, 60, 90, 120, 150, 180, 210, 240, 270 300 mins post test meal procedure, 3 times within 12 weeks treatment
measure: Fasting Lipids
timeFrame: after 12 weeks treatment
measure: Postprandial Lipids
timeFrame: after 12 weeks treatment
measure: Fasting Erythrocyte Flexibility
timeFrame: after 12 weeks treatment
measure: Postprandial Erythrocyte Flexibility
timeFrame: after 12 weeks treatment
measure: Fasting GLP-1 levels
timeFrame: after 12 weeks treatment
measure: Postprandial GLP-1 levels
timeFrame: after 12 weeks treatment
measure: Fasting cGMP
timeFrame: after 12 weeks treatment
measure: Postprandial cGMP
timeFrame: after 12 weeks treatment
measure: Fasting Calcitonin
timeFrame: after 12 weeks treatment
measure: Fasting PAI-1 levels
timeFrame: after 12 weeks treatment
measure: Postprandial PAI-1 levels
timeFrame: after 12 weeks treatment
measure: Fasting ADMA levels
timeFrame: after 12 weeks treatment
measure: Postprandial ADMA levels
timeFrame: after 12 weeks treatment
measure: Fasting Malonyldialdehyd
timeFrame: after 12 weeks treatment
measure: fasting oxidatively modified nucleosides 8-oxodG and 8-oxoGuo
timeFrame: after 12 weeks treatment
Secondary outcomes:
measure: Hypoglycemic events
timeFrame: after 12 weeks treatment
measure: Body Weight
timeFrame: after 12 weeks treatment
Other outcomes:
Locations:
city: Mainz
country: Germany
facility: ikfe GmbH
state: Rhineland-Palatinate
Study officials:
affiliation: Ikfe GmbH
name: Thomas Forst, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: