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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • RLP
    • Mainz, RLP, Germany, 55116
      • ikfe GmbH, Clinic Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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: metformin; metformin (2000 mg/day); Drug: Insulin detemir

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: ikfe-CRO GmbH
• Collaborators: IKFE Institute for Clinical Research and Development

Publications and helpful links

General Publications

• Forst T, Larbig M, Hohberg C, Forst S, Diessel S, Borchert M, Roth W, Pfutzner A. Adding insulin glargine vs. NPH insulin to metformin results in a more efficient postprandial beta-cell protection in individuals with type 2 diabetes. Diabetes Obes Metab. 2010 May;12(5):437-41. doi: 10.1111/j.1463-1326.2010.01209.x.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: July 16, 2009
• First Submitted That Met QC Criteria: July 16, 2009
• First Posted (Estimate): July 17, 2009

Study Record Updates

• Last Update Posted (Estimate): July 17, 2009
• Last Update Submitted That Met QC Criteria: July 16, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Metformin; Insulin Detemir; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef
• Other Study ID Numbers: LANT_001; EudraCT Number: 2007-006109-26