Basal Plus: Insulin Glulisine in Type 2 Diabetic Patients

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00360698
• Collaborator: (none)
• Enrollment: 106
• Locations: 3
• Arms: 2
• Duration (Months): 25
• Patients Per Site: 35.3
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

To evaluate the efficacy of a single injection of glulisine before the main meal added to insulin glargine plus oral antidiabetic drugs (OADs) compared to insulin glargine plus OADs in Type 2 diabetic patients poorly controlled with basal insulin plus OADs.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Insulin Glargine; Drug: Glimepiride; Drug: Insulin Glulisine; Drug: Metformin	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 106 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparison of Two Therapeutic Strategies for Treating Type 2 Diabetic Patients Poorly Controlled With Basal Insulin Associated With Oral Antidiabetic Drugs : 6-month Proof of Concept Study.
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Other: insulin glulisine+insulin glargine+metformin+glimepiride Bolus arm	Drug: Insulin Glargine; One daily injection at bedtime; Drug: Glimepiride; At same dosage as during the run-in period; Drug: Insulin Glulisine; One bolus given before the main meal; Drug: Metformin; At same dosage as during the run-in period
Other: insulin glargine+metformin+glimepiride Control arm	Drug: Insulin Glargine; One daily injection at bedtime; Drug: Glimepiride; At same dosage as during the run-in period; Drug: Metformin; At same dosage as during the run-in period

Outcome Measures

Primary Outcome Measures

1. Patients With Glycosylated Haemoglobin (HbA1c) Value < 7% [at the end of treatment (week 24)]

   Glycosylated Haemoglobin (HbA1c) is a biological parameter that reflects the blood glucose concentration over a long period of time. It is the standard parameter for glycemic control follow -up in diabetic patients. this parameter is expressed in percentage (%) and the target in diabetes management is to reach a HbA1c <7%

Secondary Outcome Measures

1. Glycosylated Haemoglobin (HbA1c) Value [at the end of treatment (week 24)]

2. Change in Glycosylated Haemoglobin (HbA1c) Value [from baseline to the end of treatment (week 24)]

3. Daily Mean Plasma Glucose [at the end of treatment (week 24)]

4. Change in Daily Mean Plasma Glucose [from baseline to the end of treatment (week 24)]

5. Change in Weight [from baseline to the end of treatment (week 24)]

6. Daily Dose of Insulin Glargine [at the end of treatment (week 24)]

   Mean of 3 daily doses reported during the week prior to the final visit

7. Daily Dose of Insulin Glulisine [at the end of treatment (week 24)]

   Mean of 3 daily doses reported during the week prior to the final visit

8. Rate of Symptomatic Hypoglycemia With Plasma Glucose < 70mg/dL [during treatment period (12 weeks)]

9. Rate of Nocturnal Symptomatic Hypoglycemia With Plasma Glucose < 70mg/dL [during treatment period (12 weeks)]

10. Rate of Severe Symptomatic Hypoglycemia [during treatment period (12 weeks)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diabetes Mellitus, Type 2

• 25 < BMI < 45 kg/m²

• 7,5% < HbA1c < 9%

• Treated with a basal insulin (NPH, Insulin Zinc, Insulin glargine or Insulin detemir), and at least 1g metformin daily, for more than 3 months

Exclusion Criteria:

• Type 1 diabetes mellitus

• Treatment with OADs only

• Treatment with thiazolidinediones, with exenatide or with pramlintide

• Treatment with an insulin other than basal insulin (Premix, rapid insulin, fast-acting insulin analogue)

• Active proliferative diabetic retinopathy,

• 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 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

• Previous treatment with insulin glulisine

• 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

• Impaired renal function

• History of drug or alcohol abuse

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sanofi-aventis	Bridgewater	New Jersey	United States	08807
2	Sanofi-Aventis	Moscow		Russian Federation
3	Sanofi-aventis	Guildford		United Kingdom

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: PILORGET Valérie, MD, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00360698
• Other Study ID Numbers: HMR1964A_4002; EUDRACT # : 2005-002614-38
• First Posted: Aug 7, 2006
• Last Update Posted: Aug 8, 2011
• Last Verified: Aug 1, 2011

• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Metformin; Insulin Glargine; Glimepiride; Insulin glulisine

Study Results

Participant Flow

Pre-assignment Detail	During Run-In period patients were not assigned to a treatment group. They were all treated with Insulin Glargine + Metformin + Glimepiride.

Arm/Group Title	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride	Insulin Glargine+Metformin+Glimepiride
Arm/Group Description	Insulin Glulisine (One daily injection at main meal) + Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)	Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)
Period Title: Run-In
STARTED	0	135
COMPLETED	0	125
NOT COMPLETED	0	10
Period Title: Run-In
STARTED	49	57
COMPLETED	48	56
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride	Insulin Glargine+Metformin+Glimepiride	Total
Arm/Group Description	Insulin Glulisine (One daily injection at main meal) + Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)	Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)	Total of all reporting groups
Overall Participants	49	57	106
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.6 (6.73)	59.3 (8.84)	59.9 (7.92)
Sex: Female, Male (Count of Participants)
Female	29 59.2%	35 61.4%	64 60.4%
Male	20 40.8%	22 38.6%	42 39.6%
Region of Enrollment (participants) [Number]
United States	23 46.9%	27 47.4%	50 47.2%
United Kingdom	11 22.4%	14 24.6%	25 23.6%
Russian Federation	15 30.6%	16 28.1%	31 29.2%
Body Mass Index (BMI) (kg/m²) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m²]	33.2 (5.30)	33.3 (4.39)	33.3 (4.80)
Daily Mean Plasma Glucose (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	170.2 (27.86)	167.4 (39.41)	169 (34.33)
Duration of diabetes (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.1 (7.29)	11.0 (7.02)	11.5 (7.13)
Glycosylated Haemoglobin (HbA1c) (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]	7.8 (0.60)	8.0 (0.67)	7.9 (0.64)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	91.5 (16.60)	92.9 (17.15)	92.3 (16.83)

Outcome Measures

1. Primary Outcome

Title	Patients With Glycosylated Haemoglobin (HbA1c) Value < 7%
Description	Glycosylated Haemoglobin (HbA1c) is a biological parameter that reflects the blood glucose concentration over a long period of time. It is the standard parameter for glycemic control follow -up in diabetic patients. this parameter is expressed in percentage (%) and the target in diabetes management is to reach a HbA1c <7%
Time Frame	at the end of treatment (week 24)

Outcome Measure Data

Analysis Population Description

Modified Intent to treat (ITT) population, LOCF (Last Observation Carried Forward)

Arm/Group Title	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride	Insulin Glargine+Metformin+Glimepiride
Arm/Group Description	Insulin Glulisine (One daily injection at main meal) + Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)	Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)
Measure Participants	49	57
Number [percentage of participants]	22.4 45.7%	8.8 15.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride, Insulin Glargine+Metformin+Glimepiride
	Comments	The null-hypothesis stated no differences between the 2 treatment groups regarding the percentage of patients with Glycosylated Haemoglobin (HbA1c) level <7%. A sample size of 98 randomized (49/arm) patients would allow to demonstrate with 80% power that 40 % of patients in the Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride group would achieve a HbA1c level < 7 % compared to 15 % of patients in the Insulin Glargine+Metformin+Glimepiride group(5% alpha risk, 2-sided test).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0499
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	13.68
	Confidence Interval	() 95%; 0.01 to 28.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in percentage between groups: Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride group - Insulin Glargine+Metformin+Glimepiride group

2. Secondary Outcome

Title	Glycosylated Haemoglobin (HbA1c) Value
Time Frame	at the end of treatment (week 24)

Outcome Measure Data

Analysis Population Description

Modified ITT population, LOCF

Arm/Group Title	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride	Insulin Glargine+Metformin+Glimepiride
Arm/Group Description	Insulin Glulisine (One daily injection at main meal) + Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)	Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)
Measure Participants	49	57
Mean (Standard Deviation) [percent]	7.5 (0.64)	7.8 (0.85)

3. Secondary Outcome

Title	Change in Glycosylated Haemoglobin (HbA1c) Value
Time Frame	from baseline to the end of treatment (week 24)

Outcome Measure Data

Analysis Population Description

Modified ITT population, LOCF

Arm/Group Title	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride	Insulin Glargine+Metformin+Glimepiride
Arm/Group Description	Insulin Glulisine (One daily injection at main meal) + Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)	Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)
Measure Participants	49	57
Least Squares Mean (Standard Error) [percent]	-0.37 (0.085)	-0.11 (0.078)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride, Insulin Glargine+Metformin+Glimepiride
	Comments	The null-hypothesis stated no difference between the 2 treatment groups regarding the adjusted mean change from baseline in Glycosylated Haemoglobin (HbA1c) at the end of treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments	Threshold for statistical significance (alpha) = 0.05 ; 2 sided-test
	Method	ANCOVA
	Comments	The analysis is an ANCOVA analysis on the change with group as fixed effect and baseline HbA1c as covariate
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.26
	Confidence Interval	() 95%; -0.49 to -0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.116
	Estimation Comments	Difference between groups: Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride group - Insulin Glargine+Metformin+Glimepiride group

4. Secondary Outcome

Title	Daily Mean Plasma Glucose
Time Frame	at the end of treatment (week 24)

Outcome Measure Data

Analysis Population Description

Modified ITT population, LOCF

Arm/Group Title	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride	Insulin Glargine+Metformin+Glimepiride
Arm/Group Description	Insulin Glulisine (One daily injection at main meal) + Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)	Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)
Measure Participants	47	55
Mean (Standard Deviation) [mg/dL]	154.7 (28.62)	165.8 (37.48)

5. Secondary Outcome

Title	Change in Daily Mean Plasma Glucose
Time Frame	from baseline to the end of treatment (week 24)

Outcome Measure Data

Analysis Population Description

Modified ITT population, LOCF

Arm/Group Title	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride	Insulin Glargine+Metformin+Glimepiride
Arm/Group Description	Insulin Glulisine (One daily injection at main meal) + Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)	Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)
Measure Participants	47	55
Least Squares Mean (Standard Error) [mg/dL]	-15.01 (3.661)	-2.07 (3.384)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride, Insulin Glargine+Metformin+Glimepiride
	Comments	The null-hypothesis stated no differences between the 2 treatment groups regarding the adjusted mean change from baseline in daily mean plasma glucose at the end of treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0109
	Comments	Threshold for statistical significance (alpha) = 0.05 ; 2 sided-test
	Method	ANCOVA
	Comments	The analysis is an ANCOVA analysis on the change with group as fixed effect and baseline daily mean plasma glucose as covariate
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-12.94
	Confidence Interval	() 95%; -22.83 to -3.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.987
	Estimation Comments	Difference between groups: Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride group - Insulin Glargine+Metformin+Glimepiride group

6. Secondary Outcome

Title	Change in Weight
Time Frame	from baseline to the end of treatment (week 24)

Outcome Measure Data

Analysis Population Description

Modified ITT population, LOCF

Arm/Group Title	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride	Insulin Glargine+Metformin+Glimepiride
Arm/Group Description	Insulin Glulisine (One daily injection at main meal) + Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)	Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)
Measure Participants	48	56
Least Squares Mean (Standard Error) [kg]	0.46 (0.316)	0.22 (0.293)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride, Insulin Glargine+Metformin+Glimepiride
	Comments	The null-hypothesis stated no differences between the 2 treatment groups regarding the adjusted mean change from baseline in weight at the end of treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5762
	Comments	Threshold for statistical significance (alpha) = 0.05 ; 2 sided-test
	Method	ANCOVA
	Comments	The analysis is an ANCOVA analysis on the change with group as fixed effect and baseline weight as covariate
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.24
	Confidence Interval	() 95%; -0.61 to 1.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.431
	Estimation Comments	Difference between groups: Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride group - Insulin Glargine+Metformin+Glimepiride group

7. Secondary Outcome

Title	Daily Dose of Insulin Glargine
Description	Mean of 3 daily doses reported during the week prior to the final visit
Time Frame	at the end of treatment (week 24)

Outcome Measure Data

Analysis Population Description

Modified ITT population, LOCF

Arm/Group Title	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride	Insulin Glargine+Metformin+Glimepiride
Arm/Group Description	Insulin Glulisine (One daily injection at main meal) + Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)	Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)
Measure Participants	49	57
Mean (Standard Deviation) [units of insulin glargine per day]	54.7 (34.84)	62.2 (34.85)

8. Secondary Outcome

Title	Daily Dose of Insulin Glulisine
Description	Mean of 3 daily doses reported during the week prior to the final visit
Time Frame	at the end of treatment (week 24)

Outcome Measure Data

Analysis Population Description

Modified ITT population, LOCF

Arm/Group Title	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride	Insulin Glargine+Metformin+Glimepiride
Arm/Group Description	Insulin Glulisine (One daily injection at main meal) + Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)	Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)
Measure Participants	49	0
Mean (Standard Deviation) [units of insulin glulisine per day]	12.8 (6.59)

9. Secondary Outcome

Title	Rate of Symptomatic Hypoglycemia With Plasma Glucose < 70mg/dL
Time Frame	during treatment period (12 weeks)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride	Insulin Glargine+Metformin+Glimepiride
Arm/Group Description	Insulin Glulisine (One daily injection at main meal) + Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)	Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)
Measure Participants	49	57
Mean (Standard Deviation) [Number of hypoglycemia per patient-year]	8.19 (14.603)	7.68 (13.996)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride, Insulin Glargine+Metformin+Glimepiride
	Comments	The null-hypothesis stated no difference between the 2 treatment groups regarding the rate of symptomatic hypoglycemia with plasma glucose <70 mg/dL during the treatment period.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.958
	Comments	Threshold for statistical significance (alpha) = 0.05 ; 2 sided-test
	Method	Wilcoxon (Mann-Whitney)
	Comments

10. Secondary Outcome

Title	Rate of Nocturnal Symptomatic Hypoglycemia With Plasma Glucose < 70mg/dL
Time Frame	during treatment period (12 weeks)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride	Insulin Glargine+Metformin+Glimepiride
Arm/Group Description	Insulin Glulisine (One daily injection at main meal) + Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)	Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)
Measure Participants	49	57
Mean (Standard Deviation) [Number of hypoglycemia per patient-year]	1.62 (3.418)	3.95 (9.339)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride, Insulin Glargine+Metformin+Glimepiride
	Comments	The null-hypothesis stated no difference between the 2 treatment groups regarding the rate of nocturnal symptomatic hypoglycemia with plasma glucose <70 mg/dL during the treatment period.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.302
	Comments	Threshold for statistical significance (alpha) = 0.05 ; 2 sided-test
	Method	Wilcoxon (Mann-Whitney)
	Comments

11. Secondary Outcome

Title	Rate of Severe Symptomatic Hypoglycemia
Time Frame	during treatment period (12 weeks)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride	Insulin Glargine+Metformin+Glimepiride
Arm/Group Description	Insulin Glulisine (One daily injection at main meal) + Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)	Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)
Measure Participants	49	57
Mean (Standard Deviation) [Number of hypoglycemia per patient-year]	0.00 (0.000)	0.20 (1.096)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride, Insulin Glargine+Metformin+Glimepiride
	Comments	The null-hypothesis stated no difference between the 2 treatment groups regarding the rate of severe symptomatic hypoglycemia during the treatment period.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.192
	Comments	Threshold for statistical significance (alpha) = 0.05 ; 2 sided-test
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Arm/Group Title	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride		Insulin Glargine+Metformin+Glimepiride
Arm/Group Description	Insulin Glulisine (One daily injection at main meal) + Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)		Insulin Glargine (One daily injection at bedtime) + Metformin (At same dosage as during the run-in period) + Glimepiride (At same dosage as during the run-in period)
All Cause Mortality
	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride		Insulin Glargine+Metformin+Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride		Insulin Glargine+Metformin+Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/49 (2%)		2/57 (3.5%)
Cardiac disorders
Angina Pectoris	1/49 (2%)		0/57 (0%)
Atrial Fibrillation	1/49 (2%)		0/57 (0%)
Musculoskeletal and connective tissue disorders
Scleroderma	0/49 (0%)		1/57 (1.8%)
Tendon Disorder	0/49 (0%)		1/57 (1.8%)
Other (Not Including Serious) Adverse Events
	Insulin Glulisine+Insulin Glargine+Metformin+Glimepiride		Insulin Glargine+Metformin+Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/49 (0%)		0/57 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.