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

Phase 4

Completed

• Conditions: Type 2 Diabetic Patients; Insufficient Metabolic Control; OAD Treatment
• Interventions: Drug: Insulin Glargin; Drug: NPH insulin; Drug: Insulin detemir; Drug: metformin

• Registration Number: NCT00941148
• Lead Sponsor: ikfe-CRO GmbH

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-04
• Primary Completion: 2009-03
• Study Completion: 2009-03
• Status Verified: 2009-07
• Study First Submitted: 2009-07-16
• Study First Submitted QC: 2009-07-16
• Last Update Submitted: 2009-07-16
• Study First Posted: 2009-07-17
• Last Update Posted: 2009-07-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Insulin glargine	Insulin Glargin	Insulin glargine, dose individually adapted to reach treatment goal (FBG \< 100 mg/dL)
Insulin glargine	metformin	Insulin glargine, dose individually adapted to reach treatment goal (FBG \< 100 mg/dL)
NPH Insulin	NPH insulin	NPH Insulin, dose individually adapted to reach treatment goal (FBG \< 100 mg/dL)
Insulin detemir	Insulin detemir	Insulin detemir, dose individually adapted to reach treatment goal (FBG \< 100 mg/dL)
Insulin detemir	metformin	Insulin detemir, dose individually adapted to reach treatment goal (FBG \< 100 mg/dL)
NPH Insulin	metformin	NPH Insulin, dose individually adapted to reach treatment goal (FBG \< 100 mg/dL)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

ikfe GmbH, Clinic Department; 🇩🇪 Mainz, RLP, Germany