Beta Cell Relieving and Cardiovascular Protective Effects of LANTUS Treatment in Type 2 Diabetes Patients
NCT ID: NCT01206712
Last Updated: 2010-09-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
106 participants
OBSERVATIONAL
2009-11-30
2010-07-31
Brief Summary
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Detailed Description
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A number of population based studies showed that intact proinsulin is a strong predictor of coronary heart disease in diabetic, and in non-diabetic patients. In a clinical trial investigating human proinsulin as a therapeutic approach for the treatment of diabetes mellitus an eight fold increase in CVD was found during treatment with human proinsulin compared to human regular insulin, indicating a thrombo-embolic potential of intact proinsulin. In a recent investigation an association could be confirmed between increased proinsulin plasma concentrations and the severity of angiographical characterised CHD.
Even the exact mechanism how proinsulin is involved in the pathogenesis of atherosclerosis is not completely recognized, it was already shown that PAI-1 activity increases after proinsulin administration in vitro, and there is increasing evidence that the atherogenic effects of proinsulin might be linked to increasing plasminogen activator inhibitor-1 (PAI-1) levels with subsequent inhibition of fibrinolysis and an augmented thrombogenic potency.
Treatment with sulfonylurea increases intact proinsulin secretion, and in a couple of studies, sulfonylurea treatment was found to be associated with an increased cardiovascular risk. In contrast, several studies have shown that after the introduction of insulin treatment in type 2 diabetic patients intact proinsulin levels and plasma PAI 1 levels decline, indicating not only beta cell protection, but also antiatherogenic properties of insulin. In a recent study, we have shown that treatment with basal insulin in combination with metformin effectively reduces intact proinsulin levels, and that insulin glargine is superior to NPH insulin in controlling postprandial release of intact proinsulin over an entire day.
Recently a new therapeutic concept using DPP IV inhibitors in combination with metformin has been introduced in the treatment of type 2 diabetic patients. There is some evidence that, in the beta cell, DPP IV Inhibitors might improve the conversion of intact Proinsulin into Insulin and C-peptide and thereby reduce circulating intact proinsulin levels. Since the number of type 2 diabetic patients treated with DPP-IV inhibitors is steadily increasing, there is a need to generate more data on the postprandial release of intact proinsulin in patients treated with DPP-IV inhibitors compared to Insulin or sulfonylurea treatment.
The rationale of the study is to investigate the effect of glargine and metformin treatment compared to sulfonylurea and metformin treatment and compared to DPP-4 inhibitor and metformin treatment on postprandial intact proinsulin release and postprandial PAI-1 levels. Accompanying a comparison of postprandial intact proinsulin release and the time course of postprandial PAI-levels in between all three antidiabetic treatment groups and a non-diabetic control group will be performed as well.
Conditions
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Study Design
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CASE_CONTROL
PROSPECTIVE
Study Groups
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T2DM patients treated with LANTUS + MET
T2DM patients treated with LANTUS + Metformin(MET) in their routine antidiabetic therapy. These patients do not receive any study specific medication.
No interventions assigned to this group
T2DM patients treated with SU + MET
T2DM patients treated with Sulfonylurea (SU) + Metformin(MET)in their routine antidiabetic therapy. These patients do not receive any study specific medication.
No interventions assigned to this group
T2DM patients treated with DPP-4 + MET
T2DM patients treated with Dipeptidylpeptidase 4 inhibitors (DPP-4) + Metformin(MET) in their routine antidiabetic therapy. These patients do not receive any study specific medication.
No interventions assigned to this group
Healthy subjects
healthy volunteres who do not receive any antidiabetic medication in their routine therapie.
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
2.1. Fasting blood glucose £ 100 mg/dl (5.6 mmol/l) 2.2. Oral Glucose Tolerance Test (OGTT) revealed no IGT or DM
3. Age of 40-75 years inclusively
4. BMI between 20 and 35 kg/m2 inclusively
5. Patient informed consent
Exclusion Criteria
2.1. Type 1 or type 2 diabetes mellitus (checked by oGTT) 2.2. Impaired Glucose Tolerance (IGT, checked by oGTT) 2.3. Impaired Fasting Glucose (IFG, checked by oGTT)
3. History of drug or alcohol abuse within the last five years prior to screening
4. History of severe or multiple allergies
5. Treatment with any other investigational drug within 3 months prior to screening
6. Progressive fatal disease
7. Known psychiatric illness
8. History of significant cardiovascular, respiratory, gastrointestinal, hepatic (ALAT and/or ASAT \> 3 times the normal reference range), renal (creatinine \> 1.1 mg/dl in women and \> 1.5 mg/dl in men), neurological, psychiatric and/or haematological disease as judged by the investigator
9. Pregnancy or breast feeding
10. Sexually active women of childbearing potential not consistently and correctly practicing birth control by implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomised partner
11. Lack of compliance or other similar reason, that according to investigator, precludes satisfactory participation in the study
40 Years
75 Years
ALL
Yes
Sponsors
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Sanofi
INDUSTRY
IKFE Institute for Clinical Research and Development
OTHER
ikfe-CRO GmbH
INDUSTRY
Responsible Party
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IKFE Institute for Clinical Research and Development
Principal Investigators
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Thomas Forst, Prof. MD
Role: PRINCIPAL_INVESTIGATOR
IKFE Institute for Clinical Research and Development
Locations
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IKFE Institute for Clinical Research and Development
Mainz, , Germany
Countries
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Other Identifiers
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SAN-FORST-001
Identifier Type: -
Identifier Source: org_study_id