Establishing Cardiovascular Biomarkers to Define Preferred Lantus® Use

Establishing Cardiovascular Biomarkers to Define Preferred Lantus® Use.

The aim of this study is to observe changes in cardiovascular biomarkers during treatment with Lantus in patients with Type 2 Diabetes mellitus.

• Phase IV
• Indication: Diabetes mellitus Type 2
• Primary objective:

To compare fasting intact proinsulin secretion at the beginning and after a 24 week treatment period.

- Secondary objectives: To evaluate changes in the parameters

• insulin,
• glucose,
• intact proinsulin (after a glucose challenge),
• hsCRP,
• adiponectin,
• MMP-9,
• HbA1c,
• weight

after 24 weeks of treatment.

To investigate the changes of

• glucose,
• intact proinsulin,
• hsCRP,
• adiponectin,
• HbA1c
• weight

between visit 2 (baseline), visit 6 (12 weeks) and visit 8 (final visit after 24 weeks).

To investigate the number of patients with normal values for parameters hsCRP, adiponectin, and intact proinsulin after 24 weeks of treatment (responder rates).

-Primary efficacy variable: Fasting intact proinsulin concentration at timepoint Visit 2 (Baseline) and Visit 8 (after 24 week treatment)

-Secondary efficacy variables: All secondary parameters will be assessed after 24 weeks of treatment and compared versus baseline assessment.

• Weight
• hsCRP
• Adiponectin
• MMP-9
• OGTT parameters (insulin, intact proinsulin, glucose at time point 0, 60 and 120 minutes after 24 weeks
• HOMA-IR score
• HbA1c

Additionally the following parameters will be assessed at visit 6 and will be compared with visit 2 and visit 8:

• Weight
• hsCRP
• Adiponectin
• Fasting intact Proinsulin
• Glucose
• HbA1c
• Safety Variables:
• Adverse Events
• Hypoglycaemic events

Medication/Dosage:

Insulin glargine, dose individually adapted to reach treatment goal (FBG ≤ 100 mg/dL)NPH Insulin, dose individually adapted to reach treatment goal (FBG ≤ 100 mg/dL)Insulin glulisine, dose individually adapted to reach treatment goal (FBG ≤ 100 mg/dL)Human Insulin, dose individually adapted to reach treatment goal (FBG ≤ 100 mg/dL)

-Study Duration: Duration of study participation for one patient is approximately 26 weeks. Overall total duration of the study is approximately 10 months.

Design:

This is a randomized in four arms, open-label, multi-center study. Population Patients with Type 2 Diabetes mellitus, Sample Size n = 60 (15 per arm)

Inclusion Criteria:

• Give written informed consent.
• Patient consents that his/her family physician/diabetologist will be informed of trial participation
• Type-2 diabetes mellitus ≥ 1 year of diagnosis (male and female)
• Experienced in self blood glucose measurement for ≥ 3 months.
• HbA1c ≤ 9% and >6,5%
• BMI > 30 kg/m²
• Age ≥ 18 years
• Waist circumference > 88 cm (female) and > 102 cm (male)
• NPH insulin treatment plus 1 or 2 OAD (except TZD)

Exclusion Criteria:

• History of drug or alcohol abuse within the last five years prior to screening
• Anamnestic history of hypersensitivity to the study drugs (or any component of the study drug) 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 >1.6 mg/dl in men), neurological, psychiatric and/or hematological disease as judged by the investigator
• Pregnant or lactating women
• 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 vasectomized partner
• Treatment with GLP1-analog or Thiazolidinediones (TZD)
• hsCRP > 10 mg/l (by rapid test at screening visit).
• Lack of compliance or other similar reason that, according to investigator, precludes satisfactory participation in the study
• Type 1 Diabetes mellitus
• Patients already treated with intensified conventional insulin therapy.