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

IKFE Institut für klinische Forschung und Entwicklung

Status and phase: Completed; Phase 4

Conditions: Type 2 Diabetic Patients; OAD Treatment; Insufficient Metabolic Control

Treatments: Drug: Insulin detemir; Drug: Insulin Glargin; Drug: NPH insulin; Drug: metformin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00941148

LANT_001

EudraCT Number: 2007-006109-26

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: All

Ages: 40 to 75 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

Insulin glargine

Active Comparator group

Description:

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

Treatment:

Drug: Insulin Glargin

Drug: metformin

NPH Insulin

Active Comparator group

Description:

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

Treatment:

Drug: NPH insulin

Drug: metformin

Insulin detemir

Active Comparator group

Description:

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

Treatment:

Drug: Insulin detemir

Drug: metformin