Diabetes Mellitus Type 2
Conditions
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.
Interventions
DRUGLinagliptin
Linagliptin dosed 5 mg as add on therapy to an existing metformin therapy
DRUGGlimepiride
Glimepiride 1-4mg (individually dosed) as add on therapy to an existing metformin therapy
Sponsors
ikfe-CRO GmbH
Boehringer Ingelheim
Marcus Borchert
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| fasting oxidatively modified nucleosides 8-oxodG and 8-oxoGuo | after 12 weeks treatment |
| Postprandial ADMA levels | after 12 weeks treatment |
| Fasting Malonyldialdehyd | after 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 |
| Fasting intact Proinsulin levels | after 12 weeks treatment |
| Fasting Proinsulin/Insulin Ratio | 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 |
| Fasting Lipids | after 12 weeks treatment |
| Postprandial Lipids | after 12 weeks treatment |
| Fasting Erythrocyte Flexibility | after 12 weeks treatment |
| Postprandial Erythrocyte Flexibility | after 12 weeks treatment |
| Fasting GLP-1 levels | after 12 weeks treatment |
| Postprandial GLP-1 levels | after 12 weeks treatment |
| Fasting cGMP | after 12 weeks treatment |
| Postprandial cGMP | after 12 weeks treatment |
| Fasting Calcitonin | after 12 weeks treatment |
| Fasting PAI-1 levels | after 12 weeks treatment |
| Postprandial PAI-1 levels | after 12 weeks treatment |
| Fasting ADMA levels | after 12 weeks treatment |
Secondary
| Measure | Time frame |
|---|---|
| Body Weight | after 12 weeks treatment |
| Hypoglycemic events | after 12 weeks treatment |
Countries
Germany
Contacts
Primary ContactThomas Forst, MD, PhD
Backup ContactClaudia Forkel
Outcome results
None listed