Insulin Glargine Injection Treatment in Place of Thiazolidinedione (TZD), Sulfonylurea, or Metformin in Triple Agent Therapy for Type 2 Diabetes Mellitus (T2DM) Adult Subjects With Unsatisfactory Control

Phase 4

Terminated

Conditions: Diabetes Mellitus, Type 2

Interventions: Drug: Insulin Glargine
Drug: Insulin Glulisine

Registration Number: NCT00283049

Lead Sponsor: Sanofi

Brief Summary: The purpose of this study is to compare the change in hemoglobin A1c (HbA1c) from baseline to Week 12 between the 3 treatment arms.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 390

Inclusion Criteria

Subjects meeting all of the following criteria will be considered for enrollment into the study:

18 to 79 years of age, inclusive
Diagnosis of type 2 diabetes mellitus
Continuous treatment with therapeutic dosages of a thiazolidinedione (rosiglitazone or pioglitazone), metformin, and a sulfonylurea daily prior to entering the study
Screening HbA1c ≥ 7.0%
Fasting C-peptide concentration ≥ 0.27 ng/ml
Negative glutamic acid decarboxylase (GAD) antibodies
Demonstrated ability and willingness to perform self-monitoring blood glucose (SMBG) using a plasma-referenced glucose meter and to maintain an electronic diary
Demonstrated ability and willingness to use an electronic diary to record SMBG results, insulin doses, and hypoglycemic events.
Signed, informed consent and Health Insurance Portability and Accountability Act (HIPAA) documentation

Exclusion Criteria

Stroke, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or angina pectoris, within the last 12 months
Cardiac status New York Heart Association (NYHA) III-IV
Impaired renal function as shown by, but not limited to, serum creatinine ≥ 1.5 mg/dL for males, or ≥ 1.4 mg/dL for females
Chronic use of insulin: (more than 3 weeks of continuous use) in the past 12 months
Acute infection
Clinically significant peripheral edema
Acute or chronic history of metabolic acidosis, including diabetic ketoacidosis
Clinical evidence of active liver disease, or serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2.5 times the upper limit of the normal range
History of hypoglycemia unawareness
Pregnancy or lactation
Known hypersensitivity to insulin glargine or any of the components of Lantus®
Known hypersensitivity to insulin glulisine or any of the components of Apidra®
Any malignancy within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or adequately treated cervical carcinoma in situ
Current addiction or current alcohol abuse, or history of substance or alcohol abuse within the last 2 years
Diagnosis of dementia
Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol
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 is currently taking or was treated with the following medications 3 months prior to screening: Byetta(exenatide), Starlix(nateglinide),Prandin (repaglinide), Januvia(sitagliptin), Janumet(metformin + sitagliptin)
Any disease or condition that in the opinion of the investigator and/or sponsor may interfere with the completion of the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Insulins + Sulfonylurea (SU) + Thiazolidinedione (TZD)	Insulin Glargine	Arm 1: Insulin glargine administered subcutaneously once daily plus a sulfonylurea and a TZD. Insulin glulisine will be added after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c \>6.5%)
Insulins + Sulfonylurea (SU) + Thiazolidinedione (TZD)	Insulin Glulisine	Arm 1: Insulin glargine administered subcutaneously once daily plus a sulfonylurea and a TZD. Insulin glulisine will be added after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c \>6.5%)
Insulins + Metformin (MET) + Thiazolidinedione (TZD)	Insulin Glargine	Arm 2: Insulin glargine administered subcutaneously once daily plus metformin and a TZD. Insulin glulisine will be added after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c \>6.5%)
Insulins + Metformin (MET) + Thiazolidinedione (TZD)	Insulin Glulisine	Arm 2: Insulin glargine administered subcutaneously once daily plus metformin and a TZD. Insulin glulisine will be added after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c \>6.5%)
Insulins + Metformin (MET) + Sulfonylurea (SU)	Insulin Glulisine	Arm 3: Insulin glargine administered subcutaneously once daily plus metformin and a sulfonylurea. Insulin glulisine will be added arms after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c \>6.5%)
Insulins + Metformin (MET) + Sulfonylurea (SU)	Insulin Glargine	Arm 3: Insulin glargine administered subcutaneously once daily plus metformin and a sulfonylurea. Insulin glulisine will be added arms after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c \>6.5%)

Primary Outcome Measures

Name	Time	Method
Change in Hemoglobin A1c (HbA1c) From Baseline to Week 12	12 weeks from Baseline

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects Achieving an HbA1C Less Than (<) 7.0% and Less Than (<) 6.5%	60 weeks from Baseline
Change From Baseline to End of Study and to Individual Time Points in Components of Lipid Profile (Total Cholesterol, High-density Lipoprotein Cholesterol [HDL], Low-density Lipoprotein Cholesterol [LDL], Triglycerides, LDL Subfractions)	60 weeks from Baseline
Change From Baseline to Study Time Points in 7-point Blood Glucose (BG) Profile (Before Meals, 2 Hours After Meals, at Bedtime)	60 weeks from Baseline
Change From Baseline to Individual Time Points in HbA1c, Insulin Doses, and Total Insulin Dosage	60 weeks from Baseline
Occurrences of Hypoglycemia, Symptomatic Hypoglycemia, Severe Hypoglycemia, and Serious Hypoglycemia	60 weeks from Baseline	* Symptomatic hypoglycemia (BG\<70 mg/dL, BG\<50 mg/dL): including 1 or more symptoms: headache, dizziness, general feeling of weakness, drowsiness, confusion, pallor, irritability, trembling, sweating, rapid heartbeat \& a cold, clammy feeling. * Mild-to-moderate hypoglycemia: SMBG ≥ 36 mg/dL but \<70 mg/dL * Severe hypoglycemia: assistance of another party is required \& either: * SMBG of \<36 mg/dL, or * with prompt response to treatment with oral carbohydrates, IV glucose or glucagon. * Serious hypoglycemia: * Hypoglycemia with coma/loss of consciousness Or Hypoglycemia seizure/convulsion.
Rate of Hypoglycemia, Symptomatic Hypoglycemia, Severe Hypoglycemia and Serious Hypoglycemia	60 Weeks from Baseline	* Symptomatic hypoglycemia (BG\<70 mg/dL, BG\<50 mg/dL): including 1 or more symptoms: headache, dizziness, general feeling of weakness, drowsiness, confusion, pallor, irritability, trembling, sweating, rapid heartbeat \& a cold, clammy feeling. * Mild-to-moderate hypoglycemia: SMBG ≥ 36 mg/dL but \<70 mg/dL * Severe hypoglycemia: assistance of another party is required \& either: * SMBG of \<36 mg/dL, or * with prompt response to treatment with oral carbohydrates, IV glucose or glucagon. * Serious hypoglycemia: * Hypoglycemia with coma/loss of consciousness Or Hypoglycemia seizure/convulsion.