EasyMix: Comparison of the Blood Sugar Lowering Effect of Biphasic Insulin Aspart 30 and Insulin Glargine Both Combined With Metformin and Glimepiride in Chinese and Japanese Subjects With Type 2 Diabetes New to Insulin Treatment

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01123980
• Collaborator: (none)
• Enrollment: 521
• Locations: 34
• Arms: 2
• Duration (Months): 13
• Patients Per Site: 15.3
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

This trial is conducted in Asia. The aim of this clinical trial is to investigate the blood sugar lowering effect of biphasic insulin aspart 30 once daily compared to insulin glargine once daily both in combination with metformin and glimepiride in Chinese and Japanese subjects with type 2 diabetes who have never received insulin before.

The trial is conducted as a phase 4 trial in China and phase 3 in Japan.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: biphasic insulin aspart 30; Drug: metformin; Drug: glimepiride; Drug: insulin glargine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 521 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-labelled, Randomised, Parallel Group, 3 Week run-in and 24 Week Treat-to-target Comparison of Biphasic Insulin Aspart 30 Once Daily Versus Insulin Glargine Once Daily Both in Combination With Metformin and Glimepiride in Chinese and Japanese Insulin Naive Subjects With Type 2 Diabetes
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BIAsp 30 0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride	Drug: biphasic insulin aspart 30; Treat-to-target titration according to titration algorithm. Subcutaneous (under the skin) injection once daily.; Drug: metformin; China: Tablets, 500 mg. Min. 1500 mg/day. Japan: Tablets, 250 mg. Min 500 mg/day.; Drug: glimepiride; China: Tablets, 2 mg. Min. 4 mg/day. Japan: Tablets, 1 mg. Min. 4 mg/day.
Active Comparator: Insulin glargine 0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride	Drug: metformin; China: Tablets, 500 mg. Min. 1500 mg/day. Japan: Tablets, 250 mg. Min 500 mg/day.; Drug: glimepiride; China: Tablets, 2 mg. Min. 4 mg/day. Japan: Tablets, 1 mg. Min. 4 mg/day.; Drug: insulin glargine; Treat-to-target titration according to titration algorithm. Subcutaneous (under the skin) injection once daily.

Outcome Measures

Primary Outcome Measures

1. Change in Glycosylated Haemoglobin (HbA1c) [Week 0, week 24]

Secondary Outcome Measures

1. 9-point Plasma Glucose Profiles [Week 24]

   Glycaemic control measured by 9-point plasma glucose (SPMG) profiles. The 9 timepoints for self-measurement during the day were: before breakfast, 2 hours after breakfast, before lunch, 2 hours after lunch, before dinner, 2 hours after dinner, before bedtime, at 2-4 a.m. and before breakfast the following day.

2. Percentage of Subjects Achieving HbA1c Below 7.0% [Week 24]

   The percentage of subjects achieving the treatment target for glycosylated haemoglobin A1c after 24 weeks of treatment

3. Percentage of Subjects Achieving HbA1c Below or Equal to 6.5% [Week 24]

   The percentage of subjects achieving the treatment target for glycosylated haemoglobin A1c after 24 weeks of treatment

4. Number of Hypoglycaemic Episodes - All [Weeks 0-24]

5. Number of Hypoglycaemic Episodes - Severe and Minor [Weeks 0-24]

   Hypoglycaemic episodes (hypos) summarised based on American Diabetes Association classification (severe, documented symptomatic, asymptomatic, probable symptomatic, and relative hypoglycaemia) and according to additional definition (minor hypoglycaemia). Severe hypos: requiring another person to actively administer resuscitative actions. Minor hypos: symptoms with plasma glucose below 3.1 mmol/L (56 mg/dl), or any asympomatic plasma glucose below 3.1 mmol/L.

6. Number of Hypoglycaemic Episodes [Weeks 0-24]

   All episodes classified into nocturnal (time of onset between 00:00 (included) and 05:59 (included)).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetes treated with a maximum of three different types of oral anti-diabetic drugs (OADs) (including traditional Chinese medicine which contains active ingredients of known OADs) for more than 6 months

• Unchanged total daily dose of at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) metformin for the last two months

• Unchanged total daily dose of at least half maximum recommended total daily dose of any insulin secretagogue for the last two months

• Insulin naive

• HbA1c between 7.0% and 10.0%

• FPG (fasting plasma glucose) equal to or above 6.1 mmol/L (110mg/dL)

• Body Mass Index (BMI) below 40.0 kg/m^2

Exclusion Criteria:

• Treatment with any thiazolidinedione (TZD) and GLP-1 (glucagon like peptide-1) receptor antagonists during the last 3 months before Visit 1 in this trial

• Any disease or condition which the Investigator feels would interfere with the trial

• Any contraindication to metformin or glimepiride (according to local labelling)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Beijing	Beijing	China	100029
2	Novo Nordisk Investigational Site	Beijing	Beijing	China	100101
3	Novo Nordisk Investigational Site	Beijing	Beijing	China	100191
4	Novo Nordisk Investigational Site	Beijing	Beijing	China	100700
5	Novo Nordisk Investigational Site	Beijing	Beijing	China	100853
6	Novo Nordisk Investigational Site	Chongqing	Chongqing	China	400010
7	Novo Nordisk Investigational Site	Fuzhou	Fujian	China	350025
8	Novo Nordisk Investigational Site	Harbin	Heilongjiang	China	150001
9	Novo Nordisk Investigational Site	Zhengzhou	Henan	China	450052
10	Novo Nordisk Investigational Site	Nanjing	Jiangsu	China	210012
11	Novo Nordisk Investigational Site	Nanjing	Jiangsu	China	210029
12	Novo Nordisk Investigational Site	Wuxi	Jiangsu	China	214023
13	Novo Nordisk Investigational Site	Nanchang	Jiangxi	China	330006
14	Novo Nordisk Investigational Site	Dalian	Liaoning	China	116011
15	Novo Nordisk Investigational Site	Shenyang	Liaoning	China	110004
16	Novo Nordisk Investigational Site	Shenyang	Liaoning	China	110021
17	Novo Nordisk Investigational Site	Xi'an	Shaanxi	China	710061
18	Novo Nordisk Investigational Site	Tianjin	Tianjin	China	300052
19	Novo Nordisk Investigational Site	Tianjin	Tianjin	China	300070
20	Novo Nordisk Investigational Site	Shenyang		China	110001
21	Novo Nordisk Investigational Site	Tianjin		China	300211
22	Novo Nordisk Investigational Site	Asahikawa-shi, Hokkaido		Japan	078 8510
23	Novo Nordisk Investigational Site	Chuo-ku, Tokyo		Japan	103 0002
24	Novo Nordisk Investigational Site	Gifu city, Gifu		Japan	5008717
25	Novo Nordisk Investigational Site	Higashi-ku		Japan	812 8582
26	Novo Nordisk Investigational Site	Kumamoto-shi,Kumamoto		Japan	862 0976
27	Novo Nordisk Investigational Site	Minato-ku		Japan	108 0073
28	Novo Nordisk Investigational Site	Osaka-shi, Osaka		Japan	545 8586
29	Novo Nordisk Investigational Site	Osaka-shi		Japan	5300025
30	Novo Nordisk Investigational Site	Shimotsuka-gun		Japan	321 0293
31	Novo Nordisk Investigational Site	Shimotsuke-shi, Tochigi		Japan	329 0433
32	Novo Nordisk Investigational Site	Shizuoka-shi		Japan	424 0853
33	Novo Nordisk Investigational Site	Tagajo-shi		Japan	985 0852
34	Novo Nordisk Investigational Site	Yokohama-shi		Japan	235 0045

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT01123980
• Other Study ID Numbers: BIASP-3756; U1111-1114-4112; JapicCTI-101139
• First Posted: May 14, 2010
• Last Update Posted: Feb 24, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Metformin; Insulin Glargine; Insulin Aspart; Glimepiride; Biphasic Insulins; Insulin aspart, insulin aspart protamine drug combination 30:70

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 35 sites in two countries: China (21 sites) and Japan (14 sites).
Pre-assignment Detail	At the screening, eligible subjects entered the run-in period before being randomised. During the 3 week run-in period, subjects switched from insulin secretagogue to glimepiride. During the last 2 weeks, the total dose of glimepiride was kept at 4mg/day. Subjects continued their pre-trial metformin dose.

Arm/Group Title	BIAsp 30	Insulin Glargine
Arm/Group Description	0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride	0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
Period Title: Overall Study
STARTED	261	260
COMPLETED	242	236
NOT COMPLETED	19	24

Baseline Characteristics

Arm/Group Title	BIAsp 30	Insulin Glargine	Total
Arm/Group Description	0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride	0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride	Total of all reporting groups
Overall Participants	261	260	521
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.6 (9.4)	56.1 (9.9)	56.3 (9.6)
Gender (Count of Participants)
Female	114 43.7%	119 45.8%	233 44.7%
Male	147 56.3%	141 54.2%	288 55.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	261 100%	260 100%	521 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
China	210 80.5%	212 81.5%	422 81%
Japan	51 19.5%	48 18.5%	99 19%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	165.3 (8.6)	165.2 (8.2)	165.3 (8.4)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	70.0 (11.6)	70.6 (12.5)	70.3 (12.1)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.53 (3.39)	25.76 (3.44)	25.65 (3.41)
HbA1c (glycosylated haemoglobin) at randomisation (percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	8.7 (0.88)	8.14 (0.86)	8.15 (0.87)
Duration of diabetes (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.23 (7.15)	9.47 (6.61)	9.35 (6.88)
Diabetic complications at baseline (participants) [Number]
Yes	72 27.6%	75 28.8%	147 28.2%
No	189 72.4%	185 71.2%	374 71.8%

Outcome Measures

1. Primary Outcome

Title	Change in Glycosylated Haemoglobin (HbA1c)
Time Frame	Week 0, week 24

Outcome Measure Data

Analysis Population Description

Full analysis set using LOCF (last observation carried forward) consists of all randomised subjects who were exposed to at least one dose of trial product(s)

Arm/Group Title	BIAsp 30	Insulin Glargine
Arm/Group Description	0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride	0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
Measure Participants	261	260
Least Squares Mean (Standard Error) [percentage of glycosylated haemoglobin]	-0.68 (0.06)	-0.56 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BIAsp 30, Insulin Glargine
	Comments	H0: The mean treatment difference (BIAsp 30 minus insulin glargine) > 0.4%. HA: The mean treatment difference (BIAsp 30 minus insulin glargine) =< 0.4%. Sample size was calculated to achieve a power of at least 90%, assuming an equal change in HbA1c and a common standard deviation of 1.25%
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was considered to be confirmed if the upper bound of the two-sided 95% confidence interval (CI) was below or equal to 0.4% or equivalent if the p-value for the one-sided test of H0: D > 0.4% against HA: D =< 0.4%, was less than or equal to 2.5%, where D is the mean treatment difference (investigational product minus comparator). Furthermore, superiority of BIAsp 30 OD over insulin glargine OD was shown if the upper limit of the 95% CI for the difference is lower than 0%
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	The p-values correspond to one-sided hypotheses of either non-inferiority or superiority, statistical significance level is 2.5%.
	Method	ANCOVA
	Comments	The estimates are from a normal linear regression model with treatment, country and previous OADs as factors and baseline HbA1c as a covariate
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.12
	Confidence Interval	() 95%; -0.25 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

2. Secondary Outcome

Title	9-point Plasma Glucose Profiles
Description	Glycaemic control measured by 9-point plasma glucose (SPMG) profiles. The 9 timepoints for self-measurement during the day were: before breakfast, 2 hours after breakfast, before lunch, 2 hours after lunch, before dinner, 2 hours after dinner, before bedtime, at 2-4 a.m. and before breakfast the following day.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Full analysis set using LOCF (last observation carried forward) consists of all randomised subjects who were exposed to at least one dose of the trial product(s).

Arm/Group Title	BIAsp 30	Insulin Glargine
Arm/Group Description	0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride	0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
Measure Participants	261	260
Before breakfast	6.46 (0.09)	6.49 (0.09)
2 hours after breakfast	10.18 (0.19)	10.11 (0.19)
Before lunch	7.35 (0.17)	7.22 (0.17)
2 hours after lunch	10.50 (0.20)	10.22 (0.20)
Before dinner	7.67 (0.16)	7.03 (0.16)
2 hours after dinner	9.36 (0.19)	10.88 (0.19)
Before bedtime	8.14 (0.18)	9.39 (0.18)
At 2-4 a.m.	6.58 (0.13)	7.06 (0.13)
Before breakfast the following day	6.51 (0.10)	6.35 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BIAsp 30, Insulin Glargine
	Comments	Repeated measures mixed model with an unstructured residual covarience matrix, including treatment, time, the treatment-by-time interaction, country and previous OADs as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value for parallelism is overall test for parallel time profiles between treatment groups.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.03
	Confidence Interval	() 95%; -0.24 to 0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	Before breakfast

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BIAsp 30, Insulin Glargine
	Comments	Repeated measures mixed model with an unstructured residual covarience matrix, including treatment, time, the treatment-by-time interaction, country and previous OADs as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value for parallelism is overall test for parallel time profiles between treatment groups.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.07
	Confidence Interval	() 95%; -0.45 to 0.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two hours after breakfast

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	BIAsp 30, Insulin Glargine
	Comments	Repeated measures mixed model with an unstructured residual covarience matrix, including treatment, time, the treatment-by-time interaction, country and previous OADs as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value for parallelism is overall test for parallel time profiles between treatment groups.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.14
	Confidence Interval	() 95%; -0.31 to 0.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	Before lunch

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BIAsp 30, Insulin Glargine
	Comments	Repeated measures mixed model with an unstructured residual covarience matrix, including treatment, time, the treatment-by-time interaction, country and previous OADs as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value for parallelism is overall test for parallel time profiles between treatment groups.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.28
	Confidence Interval	() 95%; -0.26 to 0.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two hours after lunch

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	BIAsp 30, Insulin Glargine
	Comments	Repeated measures mixed model with an unstructured residual covarience matrix, including treatment, time, the treatment-by-time interaction, country and previous OADs as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value for parallelism is overall test for parallel time profiles between treatment groups.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.64
	Confidence Interval	() 95%; 0.22 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Before dinner

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	BIAsp 30, Insulin Glargine
	Comments	Repeated measures mixed model with an unstructured residual covarience matrix, including treatment, time, the treatment-by-time interaction, country and previous OADs as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value for parallelism is overall test for parallel time profiles between treatment groups.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.51
	Confidence Interval	() 95%; -2.03 to -1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two hours after dinner

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	BIAsp 30, Insulin Glargine
	Comments	Repeated measures mixed model with an unstructured residual covarience matrix, including treatment, time, the treatment-by-time interaction, country and previous OADs as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value for parallelism is overall test for parallel time profiles between treatment groups.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.25
	Confidence Interval	() 95%; -1.73 to -0.78
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bedtime

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	BIAsp 30, Insulin Glargine
	Comments	Repeated measures mixed model with an unstructured residual covarience matrix, including treatment, time, the treatment-by-time interaction, country and previous OADs as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value for parallelism is overall test for parallel time profiles between treatment groups.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.47
	Confidence Interval	() 95%; -0.81 to -0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	02 - 04 a.m.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	BIAsp 30, Insulin Glargine
	Comments	Repeated measures mixed model with an unstructured residual covarience matrix, including treatment, time, the treatment-by-time interaction, country and previous OADs as factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value for parallelism is overall test for parallel time profiles between treatment groups.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.17
	Confidence Interval	() 95%; -0.06 to 0.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	Before breakfast the following day

3. Secondary Outcome

Title	Percentage of Subjects Achieving HbA1c Below 7.0%
Description	The percentage of subjects achieving the treatment target for glycosylated haemoglobin A1c after 24 weeks of treatment
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Full analysis set using LOCF (last observation carried forward) consists of all randomised subjects who were exposed to at least one dose of the trial product(s).

Arm/Group Title	BIAsp 30	Insulin Glargine
Arm/Group Description	0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride	0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
Measure Participants	261	260
Number [percentage (%) of subjects]	29.1	30.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BIAsp 30, Insulin Glargine
	Comments	The responder analysis was based on logistic regression model using treatment, country and previous OAD therapy (with or without a third OAD) as factors and baseline HbA1c as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8583
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.96
	Confidence Interval	() 95%; 0.64 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	The odds ratio and 95% confidence interval is for the HbA1c less than 7% treatment target were included.

4. Secondary Outcome

Title	Percentage of Subjects Achieving HbA1c Below or Equal to 6.5%
Description	The percentage of subjects achieving the treatment target for glycosylated haemoglobin A1c after 24 weeks of treatment
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Full analysis set using LOCF (last observation carried forward) consists of all randomised subjects who were exposed to at least one dose of the trial product(s).

Arm/Group Title	BIAsp 30	Insulin Glargine
Arm/Group Description	0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride	0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
Measure Participants	261	260
Number [percentage (%) of subjects]	14.9	14.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BIAsp 30, Insulin Glargine
	Comments	The responder analysis was based on logistic regression model using treatment, country and previous OAD therapy (with or without a third OAD) as factors and baseline HbA1c as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8013
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	() 95%; 0.64 to 1.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	The odds ratio and 95% confidence interval is for the HbA1c below or equal to 6.5% treatment target were included.

5. Secondary Outcome

Title	Number of Hypoglycaemic Episodes - All
Time Frame	Weeks 0-24

Outcome Measure Data

Analysis Population Description

The safety analysis set contains all subjects exposed to at least one dose of investigational product(s).

Arm/Group Title	BIAsp 30	Insulin Glargine
Arm/Group Description	0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride	0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
Measure Participants	261	260
Number [episodes]	745	605

6. Secondary Outcome

Title	Number of Hypoglycaemic Episodes - Severe and Minor
Description	Hypoglycaemic episodes (hypos) summarised based on American Diabetes Association classification (severe, documented symptomatic, asymptomatic, probable symptomatic, and relative hypoglycaemia) and according to additional definition (minor hypoglycaemia). Severe hypos: requiring another person to actively administer resuscitative actions. Minor hypos: symptoms with plasma glucose below 3.1 mmol/L (56 mg/dl), or any asympomatic plasma glucose below 3.1 mmol/L.
Time Frame	Weeks 0-24

Outcome Measure Data

Analysis Population Description

The safety analysis set contains all subjects exposed to at least one dose of investigational product(s).

Arm/Group Title	BIAsp 30	Insulin Glargine
Arm/Group Description	0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride	0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
Measure Participants	261	260
Severe	0	1
Minor	154	125

7. Secondary Outcome

Title	Number of Hypoglycaemic Episodes
Description	All episodes classified into nocturnal (time of onset between 00:00 (included) and 05:59 (included)).
Time Frame	Weeks 0-24

Outcome Measure Data

Analysis Population Description

The safety analysis set contains all subjects exposed to at least one dose of investigational product(s).

Arm/Group Title	BIAsp 30	Insulin Glargine
Arm/Group Description	0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride	0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
Measure Participants	261	260
Number [episodes]	97	63

Adverse Events

Time Frame	The adverse events were collected in a timespan of 24 weeks.
Adverse Event Reporting Description	The safety analysis set contains all subjects exposed to at least one dose of investigational products.
Arm/Group Title	BIAsp 30		Insulin Glargine
Arm/Group Description	0.1-0.2 U/kg (starting dose) administered once daily (OD) immediately before dinner in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride		0.1-0.2U/kg (starting dose) administered once daily (OD) at bedtime in combination with at least 1500 mg (Chinese patients) or 500 mg (Japanese patients) total daily dose of metformin and at least 4 mg glimepiride
All Cause Mortality
	BIAsp 30		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	BIAsp 30		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/261 (0.8%)		5/260 (1.9%)
Cardiac disorders
Coronary artery stenosis	0/261 (0%)	0	2/260 (0.8%)	2
Metabolism and nutrition disorders
Hypoglycaemia	0/261 (0%)	0	1/260 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adrenal adenoma	1/261 (0.4%)	1	0/260 (0%)	0
Multiple myeloma	0/261 (0%)	0	1/260 (0.4%)	1
Prostate cancer	0/261 (0%)	0	1/260 (0.4%)	1
Nervous system disorders
Cerebral infarction	1/261 (0.4%)	1	0/260 (0%)	0
Other (Not Including Serious) Adverse Events
	BIAsp 30		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/261 (10%)		28/260 (10.8%)
Infections and infestations
Nasopharyngitis	26/261 (10%)	31	28/260 (10.8%)	37

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Novo Nordisk reserves the right not to release data until specified milestones. This includes the right not to release interim results from clinical trials. At the end of the trial, one or more manuscripts for publication will be prepared in collaboration between Investigator(s) and Novo Nordisk. Novo Nordisk will not suppress or veto publications; however Novo Nordisk reserves the right to postpone publication and/or communication for a short time to protect intellectual property.