Insulin Glargine in Type 1 Diabetes Mellitus
Insulin Glargine in Type 1 Diabetes Mellitus
The primary purpose of the protocol is to demonstrate that the new regimen (insulin
 glargine+regular insulin ) is no worse than the reference regimen (insulin glargine+lys-pro
 insulin ) in reducing the incidence of severe nocturnal hypoglycemia at the end point; the
 secondary purpose is to compare the two study regimens as far as the glycemic control
 (measured by HbA1c), the daily Mean Blood Glucose (MBG) and the mean amplitude of glycemic
 excursion (MAGE index), calculated on the basis of Self Monitoring Blood Glugose (SMBG) data,
 are concerned and to verify the safety of basal insulinization with Lantus.
Inclusion criteria:

 -  Subjects with type 1 diabetes mellitus for more than three years

 -  Subjects on multiple daily injection insulin therapy, basal-bolus scheme therapy

 -  HbA1c <= 9 % (measured by central Lab, with DCCT aligned standard method)

 -  Fasting C-Peptide <= 0,1nmol/L with FBG >126 mg/dl

 -  Body Mass Index (BMI) < 30 kg/m2

 -  Willingness to accept intensive insulin therapy

 -  Ability and willingness to perform SMBG using plasma glucose meter

 -  Female subjects must be postmenopausal or under adequate contraception as judged by
 the investigator (it may be oral contraceptives, intra-uterine device or surgical
 treatment) and must have a negative serum pregnancy test

 Exclusion criteria:

 -  Diabetes other than type 1 diabetic mellitus

 -  Type 1 diabetic patients with total insulin dose >= 1 IU/kg/day

 -  Serum creatinine > 1.5 mg/dl, or history of renal transplantation or current renal
 dialysis

 -  Congestive heart failure NYHA class II

 -  Acute or chronic metabolic acidosis, including diabetic ketoacidosis

 -  Clinical evidence of active liver disease, or serum ALT/AST 2 times the upper limit of
 the normal range

 -  Hypoglycemia unawareness

 -  Pregnancy or lactation

 -  Concomitant use of β-blockers, thiazides or systemic corticosteroids

 -  More than one episode of severe hypoglycemia with seizure or coma during the past year

 -  Likelihood of requiring treatment during the study period with any anti-diabetic drug
 other than the study drugs

 -  Failure to use adequate contraception (women of current reproductive potential only)

 -  Known hypersensitivity to insulin glargine, or any of the excipients

 -  Malignancy except basal cell carcinoma within the last five years

 -  Long lasting (> 2 weeks) treatment with systemic glucocorticoid therapy

 -  Known adrenal insufficiency (interferes with hypoglycemia counter-regulation)

 -  Known hemoglobinopathy or chronic anemia because it may interfere with Hb1Ac
 determination

 -  History of substance or alcohol abuse within the last two years or current addiction
 to substances of abuse including ethanol

 -  History of positive HIV test or Hepatitis B/C test

 -  Any usage outside of the current SPC (Summary of the Product Characteristics)

 -  Any clinically relevant cardiovascular, hepatic, neurologic, endocrine, or other major
 systemic disease other than type 1 diabetic mellitus making implementation of the
 protocol or interpretation of the study results difficult

 -  History of demonstrable micro- and macro-angiopathic complications

 -  Pre-planned surgery during the study

 -  Blood donation of more than 500 ml during the previous 3 months for males or 6 months
 for females

 -  Smoker for previous 3 months

 -  Receipt of an experimental drug or use of an experimental device within the 30 days
 prior to study entry.