Lantus Versus Levemir Treat-To-Target

Study Overview
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Brief Summary
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Primary objective: To demonstrate the non-inferiority of insulin glargine in comparison to insulin detemir in term of percentage of patients who reach the target of HbA1c < 7% at the end of the treatment period and do not experience symptomatic hypoglycemia, confirmed by plasma glucose (PG) ≤ 56 mg/dL (3.1 mmol/L) Secondary objectives: To compare between the 2 treatment groups, the percentage of patients who reach the target of HbA1c < 7% and < 6.5% at the end of the treatment period To compare the changes in HbA1c and fasting plasma glucose (FPG) To compare the evolution of blood glucose profiles To compare the day to day FPG variability, the insulin doses To determine in each treatment group the biochemical and patient-related determinants of failure to reach HbA1c targets To compare the overall incidence and rate of symptomatic hypoglycemia and nocturnal symptomatic hypoglycemia confirmed by PG ≤ 56 mg/dL (3.1 mmol/L) To compare over the treatment period, the overall incidence and rate of symptomatic hypoglycemia and symptomatic nocturnal hypoglycemia (with PG ≤ 70 mg/dL [3.9 mmol/L]), of symptomatic day-time hypoglycemia (with PG ≤ 70 mg/dL and with PG ≤ 56 mg/dL), of severe hypoglycemia, of asymptomatic hypoglycemia with PG ≤ 56 mg/dL To compare the overall safety: incidence of adverse events (including serious hypoglycemia and local tolerance at injection site), change in body weight, in waist circumference and in waist / hip ratio To assess the quality of life and treatment satisfaction

Official Title
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Target Glycemic Control and the Incidence of Documented Symptomatic Hypoglycemia in Insulin naïve Subjects With Type 2 Diabetes Failing on Oral Hypoglycemic Agent(s) and Treated With Insulin Glargine or Insulin Detemir.

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin glargine
* Drug: Insulin Detemir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes for at least 1 year Insulin naïve Treated with stable doses of oral antidiabetics for at least 3 months prior to study start, including at least metformin (at least 1g/day) 7% ≤ HbA1c ≤ 10.5 % Body mass index (BMI) < 40 kg/m² Ability and willingness to perform blood glucose monitoring using a blood glucose meter and to use a patient diary Exclusion Criteria: Type 1 diabetes Current or previous use of insulin (except for previous treatment of gestational diabetes or brief treatment with insulin for less than 1 week) Treatment with glucagon-like peptide (GLP)-1 receptor agonists or with dipeptidyl peptidase (DPP)-IV inhibitors Active proliferative diabetic retinopathy, as defined by the application of photocoagulation or surgery, in the 6 months before study entry or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgery during the study (an optic fundus examination should have been performed in the 2 years prior to study entry) Pregnancy (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraceptive method) Breast-feeding History of hypersensitivity to the study drugs or to drugs with a similar chemical structure Treatment with systemic corticosteroids in the 3 months prior to study entry Treatment with any investigational product in the 2 months prior to study entry Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major disease making implementation of the protocol or interpretation of the study results difficult Impaired hepatic function as shown by Alamine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) greater than three times the upper limit of normal range at study entry Impaired renal function as shown by serum creatinine ≥ 1.5 mg/dL (≥ 133 μmol/L) in men and ≥ 1.4 mg/dL (124 μmol/L) in women at study entry History of drug or alcohol abuse in the last year The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Insulin Glargine | Drug: Insulin glargine<br>* Subcutaneous injection, once a day in the evening<br>|
| Active Comparator: 2<br>Insulin Detemir | Drug: Insulin Detemir<br>* Subcutaneous injection, twice a day at breakfast and before dinner<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c recorded |  | At baseline, week 12 and week 24 | 
| Self-monitored fasting BG in both treatment arms and pre-dinner BG in detemir arm |  | On the 4 consecutive days before each visit | 
| Self-monitored BG values from 8-point 24-hour profile recorded on 2 consecutive days |  | Within the week prior to baseline, week 12 and week 24 | 
| Episodes of hypoglycemia (symptomatic, total and categorized as day-time/nocturnal, severe or asymptomatic) |  | All across the study | 
| Self-monitored BG values whenever patient experiences symptoms possibly related to hypoglycemia. |  | All across the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Doses of insulin glargine or insulin detemir |  | Daily | 
| Laboratory fasting plasma glucose |  | At baseline, week 12 and week 24 | 
| Insulinemia and fasting C-peptide level |  | At baseline | 
| Lipid profile |  | at baseline and week 24 | 
| Patient reported outcomes (quality of life and treatment satisfaction) |  | at baseline, week 4, week 12 and at the last visit | 
| Safety data: occurrence of adverse events and weight |  | assessed at each visit | 
| Waist and hip circumferences |  | measured at baseline, week 12 and week 24 | 
| Systolic and diastolic blood pressure |  | measured at study entry, baseline, week 12 and week 24 | 
| Physical examination |  | performed at study entry and at last visit. |