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

Safety and Efficacy of Insulin Glargine Injection [rDNA Origin] Treatment in Place of the TZD or the Sulfonylurea or Metformin in Triple Agent Therapy for T2DM Adult Subjects With Unsatisfactory Control

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00283049

Enrollment

390

Registered

2006-01-27

Start date

2006-02-28

Completion date

2008-11-30

Last updated

2011-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 2

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.

Interventions

DRUGInsulin Glargine

Insulin glargine administered subcutaneously once daily.

DRUGInsulin Glulisine

Insulin glulisine will be added after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c \>6.5%)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 79 Years

Healthy volunteers

Inclusion criteria

Subjects meeting all of the following criteria will be considered for enrollment into the study: 1. 18 to 79 years of age, inclusive 2. Diagnosis of type 2 diabetes mellitus 3. Continuous treatment with therapeutic dosages of a thiazolidinedione (rosiglitazone or pioglitazone), metformin, and a sulfonylurea daily prior to entering the study 4. Screening HbA1c ≥ 7.0% 5. Fasting C-peptide concentration ≥ 0.27 ng/ml 6. Negative glutamic acid decarboxylase (GAD) antibodies 7. Demonstrated ability and willingness to perform self-monitoring blood glucose (SMBG) using a plasma-referenced glucose meter and to maintain an electronic diary 8. Demonstrated ability and willingness to use an electronic diary to record SMBG results, insulin doses, and hypoglycemic events. 9. Signed, informed consent and Health Insurance Portability and Accountability Act (HIPAA) documentation

Exclusion criteria

1. Stroke, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or angina pectoris, within the last 12 months 2. Cardiac status New York Heart Association (NYHA) III-IV 3. 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 4. Chronic use of insulin: (more than 3 weeks of continuous use) in the past 12 months 5. Acute infection 6. Clinically significant peripheral edema 7. Acute or chronic history of metabolic acidosis, including diabetic ketoacidosis 8. 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 9. History of hypoglycemia unawareness 10. Pregnancy or lactation 11. Known hypersensitivity to insulin glargine or any of the components of Lantus® 12. Known hypersensitivity to insulin glulisine or any of the components of Apidra® 13. 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 14. Current addiction or current alcohol abuse, or history of substance or alcohol abuse within the last 2 years 15. Diagnosis of dementia 16. 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 17. 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 18. 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) 19. Any disease or condition that in the opinion of the investigator and/or sponsor may interfere with the completion of the study

Design outcomes

Primary

Measure	Time frame
Change in Hemoglobin A1c (HbA1c) From Baseline to Week 12	12 weeks from Baseline

Secondary

Measure	Time frame	Description
Percentage of Subjects Achieving an HbA1C Less Than (<) 7.0% and Less Than (<) 6.5%	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.
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	—

Countries

United States

Participant flow

Participants by arm

Arm	Count
SU + TZD + IG Arm 1: Insulin glargine(IG) administered subcutaneously once daily plus a sulfonylurea and a thiazolidinedione(TZD). Insulin glulisine will be added after Week 12 or later for those subjects needing additional prandial insulin therapy (HbA1c \>6.5%)	128
MET + TZD + IG Arm 2: Insulin glargine (IG) administered subcutaneously once daily plus metformin and a thiazolidinedione (TZD). Insulin glulisine will be added after Week 12 or later for those subjects needing additional prandial insulin therapy (HbA1c \>6.5%)	128
MET+SU + IG Arm 3: Insulin glargine (IG) administered subcutaneously once daily plus metformin and a sulfonylurea. Insulin glulisine will be added after Week 12 or later for those subjects needing additional prandial insulin therapy (HbA1c \>6.5%)	130
Total	386

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	6	1	4
Overall Study	Death	1	1	1
Overall Study	Discontinuation of Study	18	16	20
Overall Study	Lack of Efficacy	0	1	1
Overall Study	Lost to Follow-up	4	2	5
Overall Study	No longer requires study treatment	0	0	1
Overall Study	Protocol Violation	3	0	3
Overall Study	Withdrawal by Subject	26	24	19

Baseline characteristics

Characteristic	MET + TZD + IG	MET+SU + IG	SU + TZD + IG	Total
Age Continuous	54.7 years STANDARD_DEVIATION 10.14	54.6 years STANDARD_DEVIATION 9.41	56.1 years STANDARD_DEVIATION 9.57	55.2 years STANDARD_DEVIATION 9.71
Body Mass Index (BMI)	34.3 kg/m² STANDARD_DEVIATION 6.57	34.5 kg/m² STANDARD_DEVIATION 7.04	33.2 kg/m² STANDARD_DEVIATION 6.41	34.0 kg/m² STANDARD_DEVIATION 6.69
Duration of diabetes	9.7 years STANDARD_DEVIATION 5.68	10.5 years STANDARD_DEVIATION 6	10.5 years STANDARD_DEVIATION 6.95	10.2 years STANDARD_DEVIATION 6.23
Region of Enrollment USA	128 participants	130 participants	128 participants	386 participants
Sex: Female, Male Female	54 Participants	52 Participants	51 Participants	157 Participants
Sex: Female, Male Male	74 Participants	78 Participants	77 Participants	229 Participants
Weight	99.6 kg STANDARD_DEVIATION 20.22	101.2 kg STANDARD_DEVIATION 24.98	98.1 kg STANDARD_DEVIATION 21.46	99.6 kg STANDARD_DEVIATION 22.31

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	99 / 128	84 / 128	84 / 130
serious Total, serious adverse events	22 / 128	20 / 128	13 / 130

Outcome results

Primary

Change in Hemoglobin A1c (HbA1c) From Baseline to Week 12

Time frame: 12 weeks from Baseline

Population: Safety Population (excluding patients from Good Clinical Practice \[GCP\] non-compliant sites)

Arm	Measure	Value (MEAN)	Dispersion
Insulin Glargine + Sulfonylurea (SU) + Thiazolidinedione (TZD)	Change in Hemoglobin A1c (HbA1c) From Baseline to Week 12	-1.2 Percentage	Standard Deviation 1.72
Insulin Glargine + Metformin (MET) + Thiazolidinedione (TZD)	Change in Hemoglobin A1c (HbA1c) From Baseline to Week 12	-1.2 Percentage	Standard Deviation 1.35
Insulin Glargine + Metformin (MET) + Sulfonylurea (SU)	Change in Hemoglobin A1c (HbA1c) From Baseline to Week 12	-1.2 Percentage	Standard Deviation 1.31

Secondary