Type 2 Diabetic Patients, Insufficient Metabolic Control, OAD Treatment
Conditions
Brief summary
The aim of the study is to show that treatment with Glargine will lead to an improvement in beta cell function especially within times of maximal beta cell stress occurring after a meal. For this reason three different standardized test meals (breakfast, lunch, dinner) will be performed and the postprandial secretion of intact proinsulin levels will be measured. These measurements will be performed with patients treated in combination with metformin and insulin glargine versus metformin plus NPH insulin (within the core study) and if significant difference is observed, with a third treatment arm with metformin plus insulin detemir. Hypothesis is that the area under the curve (AUC) intact proinsulin levels within 2 hours after test meal dinner of metformin plus insulin glargin differs from AUC intact proinsulin levels of metformin plus NPH insulin.
Interventions
Sponsors
IKFE Institute for Clinical Research and Development
ikfe-CRO GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 Diabetes mellitus according to the ADA criteria * HbA1c between 6.5% and 8.5% * Individually optimized combination therapy with metformin in combination with sulfonylurea in a stable dosage within the last 3 months * Age between 40 and 75 years * Fasting intact proinsulin level \> 7 pmol/Land \< 20 pmol/Lat screening
Exclusion criteria
* Type 1 Diabetes mellitus * Pre-Treatment with insulin within the last 3 months prior to screening * Pre-Treatment with PPARy-agonists (glitazones) within the last 3 months prior to screening * Major micro- or macrovascular complications as judged by the investigator * BMI \> 40 kg/m² * Hypokalemia (K \< 3.5 mmol /L) * History of drug or alcohol abuse * Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures * History of severe or multiple allergies * Treatment with any other investigational drug within 3 months prior to screening * Progressive fatal disease * History of significant cardiovascular, respiratory, gastrointestinal, hepatic (ALAT and/or ASAT \> 3 times the normal reference range), renal (creatinine \> 1.3 mg/dL in women and \> 1.7 mg/dL in men), neurological, psychiatric and/or haematological disease as judged by the investigator * Pregnancy or breast feeding * Sexually active women of childbearing potential not actively and consistently practicing birth control by using a medically accepted device or therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| postprandial dynamics of intact proinsulin secretion after standardized test meals (AUC for two hours after dinner) | 12 +/- 2 weeks |
Secondary
| Measure | Time frame |
|---|---|
| increase of intact proinsulin after breakfast (BF), lunch (LU) and dinner (DI) | 12 +/- 2 weeks |
| Ratio of exogenous insulin vs. endogenous insulin (measurements of glargine, NPH Insulin, detemir and human insulin levels) | 12 +/- 2 weeks |
| Postprandial endothelial function measured as postischaemic response in LDF measurements (after BF, LU, DI) | 12 +/- 2 weeks |
| Postprandial change in and AUC for hs CRP (after BF, LU, DI) | 12 +/- 2 weeks |
| Postprandial change in and AUC for ADMA (after BF, LU, DI) | 12 +/- 2 weeks |
| AUC for intact proinsulin levels for two hours after a standardized test meal (breakfast and lunch) | 12 +/- 2 weeks |
| Changes in FBG | 12 +/- 2 weeks |
| Changes in 8-point BG profiles | 12 +/- 2 weeks |
| Percentage of patients reaching the treatment goal | 12 +/- 2 weeks |
| Insulin dosage per kg body weight to reach treatment goal | 12 +/- 2 weeks |
| Postprandial increase in and AUC for glucose levels (after BF, LU, DI) | 12 +/- 2 weeks |
Countries
Germany
Outcome results
None listed