Opposing Step-by-step Insulin Reinforcement to Intensified Strategy

Study Overview
=================
Brief Summary
-----------------
Primary objectives : To show the non inferiority in terms of efficacy (HbA1c) of insulin glargine plus metformin combined with 1 to 3 bolus of insulin glulisine introduced progressively (Arm 2) compared with insulin glargine plus metformin combined with 3 bolus of insulin glulisine (Arm 1), in type 2 diabetes mellitus patients poorly controlled on basal insulin therapy with oral antidiabetic drugs. To show the non inferiority in terms of efficacy (HbA1c) of insulin glargine plus metformin combined with 1 to 3 bolus of insulin glulisine introduced progressively (Arm 2) compared with insulin glargine plus metformin and insulin secretagogue (sulfonylurea or glinide) combined with 1 to 3 bolus of insulin glulisine introduced progressively (Arm 3), in type 2 diabetes mellitus patients poorly controlled on basal insulin therapy with oral antidiabetic drugs. Secondary objectives : To compare between the 3 treatment groups: evolution of HbA1c over time, percentage of subjects with HbA1c <= 7% at the end of the study, evolution of blood glucose profiles, incidence of hypoglycemia, insulin doses, evolution of body weight and treatment satisfaction.

Official Title
-----------------
Comparison of Three Therapeutic Strategies for Treating Type 2 Diabetes Mellitus Patients Poorly Controlled With Basal Insulin Associated With Oral Antidiabetic Drugs

Conditions
-----------------
Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Drug: Insulin Glargine
* Drug: Insulin Glulisine
* Drug: Metformin
* Drug: insulin secretagogue


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Type 2 diabetic BMI ≤ 40 kg/m² HbA1c > 7% Treated with basal insulin (NPH, Insulin Zinc, insulin glargine or insulin detemir), and at least, two OAD including an insulin secretagogue (sulfonylurea or glinide, at any dosage) and metformin (at the maximum tolerated dosage), for more than 6 months Exclusion criteria: Type 1 diabetes mellitus Treatment with OADs only Treatment with thiazolidinediones Treatment with an insulin other than basal insulin (Premix, rapid insulin, fast-acting insulin analogue) 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 (confirmed by an optic fundus performed in the 2 years prior study entry) Pregnancy (women of childbearing potential must have a negative pregnancy test at study entry and effective contraception) Breast-feeding History of hypersensitivity to the study drug or to drugs with a similar chemical structure or to insulin glargine Treatment with systemic corticosteroids, irrespective of the dose of administration and irrespective of the prior or foreseeable treatment duration Treatment with any investigational product in the last 2 months before study entry, except for insulin glargine 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 ALT and/or AST greater than three times the upper limit of normal at study entry Impaired renal function as shown by serum creatinine >135 μmol/l in men and > 110 μmol/l in women at study entry History of drug or alcohol abuse Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study Subject unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study Subject deprived of freedom by a judicial or administrative decision Subject is the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol. 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
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 + 3 bolus of Insulin Glulisine + Metformin | Drug: Insulin Glargine<br>* One daily injection in the evening. 100 U/ml<br>Drug: Insulin Glulisine<br>* Given immediately before each of the three main meals. 100 U/ml<br>Drug: Metformin<br>* At same dosages as the previous treatment<br>|
| Experimental: 2<br>Insulin Glargine + 1 to 3 bolus of Insulin Glulisine + Metformin | Drug: Insulin Glargine<br>* One daily injection in the evening. 100 U/ml<br>Drug: Insulin Glulisine<br>* Given immediately before each of the three main meals. 100 U/ml<br>Drug: Metformin<br>* At same dosages as the previous treatment<br>|
| Experimental: 3<br>Insulin Glargine + 1 to 3 bolus of Insulin Glulisine + Metformin + Insulin secretagogue | Drug: Insulin Glargine<br>* One daily injection in the evening. 100 U/ml<br>Drug: Insulin Glulisine<br>* Given immediately before each of the three main meals. 100 U/ml<br>Drug: Metformin<br>* At same dosages as the previous treatment<br>Drug: insulin secretagogue<br>* sulfonylurea or glinide<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c |  | From the beginning to the end of the study | 
| 24-hour blood glucose levels |  | From the beginning to the end of the study | 
| symptomatic hypoglycemia (diurnal and nocturnal) |  | From the beginning to the end of the study | 
| Severe hypoglycemia (diurnal and nocturnal), |  | From the beginning to the end of the study | 
| Insulin doses |  | From the beginning to the end of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital signs |  | From the beginning to the end of the study | 
| Adverse events |  | From the beginning to the end of the study |