Beta-Cell Function of Insulin Glargine Compared to Neutral Protamine Hagedorn (NPH) Insuline and to Insulin Detemir in Combination With Metformin

Sponsor

ikfe-CRO GmbH (Industry)

Overall Status

Completed

CT.gov ID

NCT00941148

Collaborator

IKFE Institute for Clinical Research and Development (Other)

Enrollment

Location

Arms

Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetic Patients Insufficient Metabolic Control OAD Treatment	Drug: Insulin Glargin Drug: NPH insulin Drug: Insulin detemir Drug: metformin	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Impact of Insulin (I.)Glargine Compared to NPH I. and to I. Detemir in Combination With Metformin on Prandial ß-cell Function and Overall Metabolic Control in Type 2 Diabetic Patients With Insufficient Metabolic Control During OAD Treatment

Study Start Date :

Apr 1, 2008

Actual Primary Completion Date :

Mar 1, 2009

Actual Study Completion Date :

Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Insulin glargine Insulin glargine, dose individually adapted to reach treatment goal (FBG < 100 mg/dL)	Drug: Insulin Glargin Drug: metformin metformin (2000 mg/day)
Active Comparator: NPH Insulin NPH Insulin, dose individually adapted to reach treatment goal (FBG < 100 mg/dL)	Drug: NPH insulin Drug: metformin metformin (2000 mg/day)
Active Comparator: Insulin detemir Insulin detemir, dose individually adapted to reach treatment goal (FBG < 100 mg/dL)	Drug: Insulin detemir Drug: metformin metformin (2000 mg/day)

Arm

Intervention/Treatment

Active Comparator: Insulin glargine

Insulin glargine, dose individually adapted to reach treatment goal (FBG < 100 mg/dL)

Drug: Insulin Glargin

Drug: metformin

metformin (2000 mg/day)

Active Comparator: NPH Insulin

NPH Insulin, dose individually adapted to reach treatment goal (FBG < 100 mg/dL)

Drug: NPH insulin

Drug: metformin

metformin (2000 mg/day)

Active Comparator: Insulin detemir

Insulin detemir, dose individually adapted to reach treatment goal (FBG < 100 mg/dL)

Drug: Insulin detemir

Drug: metformin

metformin (2000 mg/day)

Outcome Measures

Primary Outcome Measures

postprandial dynamics of intact proinsulin secretion after standardized test meals (AUC for two hours after dinner) [12 +/- 2 weeks]

Secondary Outcome Measures

AUC for intact proinsulin levels for two hours after a standardized test meal (breakfast and lunch) [12 +/- 2 weeks]
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]
Postprandial increase in and AUC for glucose levels (after BF, LU, DI) [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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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