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

NCT00941148 | Completed Phase 4 DMC

• 2 other identifiers: LANT_001EudraCT Number: 2007-006109-26
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetic Patients; Insufficient Metabolic Control; OAD Treatment

Outcome Measures

Primary Outcomes (1)

• postprandial dynamics of intact proinsulin secretion after standardized test meals (AUC for two hours after dinner)

  12 +/- 2 weeks

Secondary Outcomes (11)

• 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

Study Arms (3)

Insulin glargine

ACTIVE COMPARATOR

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

Drug: Insulin Glargin; Drug: metformin

NPH Insulin

ACTIVE COMPARATOR

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

Drug: NPH insulin; Drug: metformin

Insulin detemir

ACTIVE COMPARATOR

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

Drug: Insulin detemir; Drug: metformin

Interventions

Insulin Glargin DRUG

Insulin glargine

NPH insulin DRUG

NPH Insulin

Insulin detemir DRUG

Insulin detemir

metformin DRUG

metformin (2000 mg/day)

Insulin detemir; Insulin glargine; NPH Insulin

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ikfe-CRO GmbH: lead
• IKFE Institute for Clinical Research and Development: collaborator

Study Sites (1)

ikfe GmbH, Clinic Department

Mainz, RLP, 55116, Germany

Location

Related Publications (1)

• 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.

  PMID: 20415692 DERIVED

MeSH Terms

Interventions

Insulin, Isophane; Insulin Detemir; Metformin

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 16, 2009
• First Posted: July 17, 2009
• Study Start: April 1, 2008
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: July 17, 2009

Record last verified: 2009-07

Locations

DE (1)