Effect of Liraglutide in Combination With Sulfonylurea (SU) on Blood Glucose Control in Subjects With Type 2 Diabetes

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00395746
• Collaborator: (none)
• Enrollment: 264
• Location: 1
• Arms: 4
• Duration (Months): 19
• Patients Per Site Per Month: 13.9

Study Details

Study Description

Brief Summary

This trial is conducted in Japan. The trial aims for comparison of the effect on glycaemic control of liraglutide in combination with sulphonylurea agent (SU) compared to SU monotherapy, as assessed by HbA1c after 24 weeks and 52 weeks in subjects with type 2 diabetes. Liraglutide will be compared to placebo, in combination with SU. Trial has a randomisation period of 24 weeks followed by a 28 week extension period, in total 52 weeks.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: sulfonylurea; Drug: liraglutide; Drug: liraglutide	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 264 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Liraglutide in Combination With Sulfonylurea (SU) on Glycaemic Control in Subjects With Type 2 Diabetes
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Oct 1, 2007
• Actual Study Completion Date: May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0.6 mg + SU Liraglutide 0.6 mg + sulphonylurea	Drug: sulfonylurea; SU agent; Drug: liraglutide; Liraglutide 0.6 mg/day or placebo. Injected s.c. (under the skin) once daily.
Experimental: 0.9 mg + SU Liraglutide 0.9 mg + sulphonylurea	Drug: sulfonylurea; SU agent; Drug: liraglutide; Liraglutide 0.9 mg/day or placebo. Injected s.c. (under the skin) once daily.
Placebo Comparator: SU Mono - 1 Liraglutide placebo 0.6 mg + sulphonylurea	Drug: sulfonylurea; SU agent
Placebo Comparator: SU Mono - 2 Liraglutide placebo 0.9 mg + sulphonylurea	Drug: sulfonylurea; SU agent

Outcome Measures

Primary Outcome Measures

1. Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment [after 24 weeks of treatment]

Secondary Outcome Measures

1. Glycosylated Haemoglobin A1c (HbA1c) After 52 Weeks of Treatment [after 52 weeks of treatment]

2. Fasting Plasma Glucose After 24 Weeks of Treatment [after 24 weeks of treatment]

3. Fasting Plasma Glucose After 52 Weeks of Treatment [after 52 weeks of treatment]

4. Postprandial Glucose AUC After 24 Weeks of Treatment [after 24 weeks of treatment]

   Postprandial glucose AUC measured 0-3 hours after a meal after 24 weeks of treatment

5. Postprandial Glucose AUC After 52 Weeks of Treatment [after 52 weeks of treatment]

   Postprandial Glucose AUC measured 0-3 hours after a meal after 52 weeks of treatment

6. Mean PG in 7-point Plasma Glucose Profile After 24 Weeks of Treatment [after 24 weeks of treatment]

   Plasma glucose (PG) profile measured after 24 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime.

7. Mean PG in 7-point Plasma Glucose Profile After 52 Weeks of Treatment [after 52 weeks of treatment]

   7-point plasma glucose (PG) profile measured after 52 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime.

8. Mean Postprandial PG Increment in 7-point Plasma Glucose Profile After 24 Weeks of Treatment [after 24 weeks of treatment]

   Mean postprandial plasma glucose (PG) increment in 7-point plasma glucose profile, ie the mean of the difference of plasma glucose measured before and after a meal, after 24 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime.

9. Mean Postprandial PG Increment in 7-point Plasma Glucose Profile After 52 Weeks of Treatment [after 52 weeks of treatment]

   Mean postprandial plasma glucose (PG) increment in 7-point plasma glucose profile, ie the mean of the difference of plasma glucose measured before and after a meal, after 52 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime.

10. Body Weight After 24 Weeks of Treatment [after 24 weeks of treatment]

11. Body Weight After 52 Weeks of Treatment [after 52 weeks of treatment]

12. Hypoglycaemic Episodes [over 52 weeks of treatment]

    Hypoglycaemic episodes measured over 52 weeks of treatment. Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetes

• Diet/exercise therapy with sulfonylurea (SU) for at least eight weeks

• HbA1c greater than or equal to 7.0% and less than 10.0%

• BMI less than 35 kg/m2

Exclusion Criteria:

• Treatment with insulin within the last 12 weeks

• Treatment with any drug that could interfere with the glucose level

• Any serious medical condition

• Females who are pregnant, have intention of becoming pregnant or are breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Tokyo		Japan	1000005

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: NCT00395746
• Other Study ID Numbers: NN2211-1701; JapicCTI-060324
• First Posted: Nov 3, 2006
• Last Update Posted: Mar 8, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Liraglutide

Study Results

Participant Flow

Recruitment Details	49 sites in Japan
Pre-assignment Detail	Subjects included were patients with type 2 diabetes treated with diet therapy and one sulphonylurea (SU) agent (glibenclamide, gliclazide or glimepiride). Subjects continued their current SU therapy with, as a rule, no change in the dose and dosage in the study. A total of 267 subjects were randomised, 3 subjects were not exposed to study drug.

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
Period Title: Overall Study
STARTED	88	88	88
COMPLETED	78	84	66
NOT COMPLETED	10	4	22

Baseline Characteristics

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono	Total
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Total of all reporting groups
Overall Participants	88	88	88	264
Age, Customized (participants) [Number]
20-29	0 0%	1 1.1%	0 0%	1 0.4%
30-39	2 2.3%	4 4.5%	0 0%	6 2.3%
40-49	16 18.2%	5 5.7%	19 21.6%	40 15.2%
50-59	24 27.3%	27 30.7%	28 31.8%	79 29.9%
60-69	30 34.1%	32 36.4%	30 34.1%	92 34.8%
70-	16 18.2%	19 21.6%	11 12.5%	46 17.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.1 (10.3)	61.3 (11.0)	58.6 (9.7)	59.7 (10.4)
Sex: Female, Male (Count of Participants)
Female	35 39.8%	29 33%	31 35.2%	95 36%
Male	53 60.2%	59 67%	57 64.8%	169 64%
BMI (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	25.25 (3.58)	24.40 (3.37)	24.94 (3.96)	24.86 (3.65)
Body weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	66.19 (12.03)	64.53 (11.95)	66.79 (13.66)	65.84 (12.56)
Duration of diabetes (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.33 (5.77)	11.61 (7.68)	10.06 (7.28)	10.33 (7.00)
HbA1c (percentage of total haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of total haemoglobin]	8.48 (0.73)	8.26 (0.71)	8.44 (0.83)	8.39 (0.76)

Outcome Measures

1. Primary Outcome

Title	Glycosylated Haemoglobin A1c (HbA1c) After 24 Weeks of Treatment
Time Frame	after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
Measure Participants	86	87	88
Least Squares Mean (Standard Error) [percentage of total haemoglobin]	7.02 (0.10)	6.75 (0.11)	8.02 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	ANOVA model included treatment group and pre-trial SU as fixed effects and HbA1C at baseline as a covariate. Two null hypotheses were statistically tested: H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively. When the test of comparison between 0.9 mg+SU and SU mono was significant, the test of comparison between 0.6 mg+SU and SU mono was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	A significance level of a two-sided 5% was used for statistical hypothesis testing.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-1.27
	Confidence Interval	() 95%; -1.51 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	ANOVA model included treatment group and pre-trial SU as fixed effects and HbA1C at baseline as a covariate. Two null hypotheses were statistically tested: H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively. When the test of comparison between 0.9 mg+SU and SU mono was significant, the test of comparison between 0.6 mg+SU and SU mono was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	A significance level of a two-sided 5% was used for statistical hypothesis testing.
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-1.00
	Confidence Interval	() 95%; -1.24 to -0.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Glycosylated Haemoglobin A1c (HbA1c) After 52 Weeks of Treatment
Time Frame	after 52 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
Measure Participants	86	87	88
Least Squares Mean (Standard Error) [percentage of total haemoglobin]	7.42 (0.12)	7.06 (0.13)	8.39 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-1.33
	Confidence Interval	() 95%; -1.62 to -1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-0.96
	Confidence Interval	() 95%; -1.25 to -0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Fasting Plasma Glucose After 24 Weeks of Treatment
Time Frame	after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
Measure Participants	85	86	87
Least Squares Mean (Standard Error) [mg/dL]	132.2 (3.5)	126.2 (3.5)	158.8 (3.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%: H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	To perform the pairwise comparisons simultaneously, a closed testing procedure was applied. When the hypothesis μ0.9 = μ0.6 = μSU was rejected, the 2 hypotheses of pairwise comparison were tested simultaneously both at significance level of 5%.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-32.4
	Confidence Interval	() 95%; -40.5 to -24.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%: H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	To perform the pairwise comparisons simultaneously, a closed testing procedure was applied. When the hypothesis μ0.9 = μ0.6 = μSU was rejected, the 2 hypotheses of pairwise comparison were tested simultaneously both at significance level of 5%.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-26.4
	Confidence Interval	() 95%; -34.5 to -18.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Fasting Plasma Glucose After 52 Weeks of Treatment
Time Frame	after 52 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
Measure Participants	85	86	87
Least Squares Mean (Standard Error) [mg/dL]	140.3 (4.0)	134.5 (4.1)	164.6 (4.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-30.2
	Confidence Interval	() 95%; -39.6 to -20.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-24.4
	Confidence Interval	() 95%; -33.8 to -14.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Postprandial Glucose AUC After 24 Weeks of Treatment
Description	Postprandial glucose AUC measured 0-3 hours after a meal after 24 weeks of treatment
Time Frame	after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
Measure Participants	83	84	71
Least Squares Mean (Standard Error) [mg/dL *h]	614.58 (14.75)	575.50 (15.01)	725.72 (15.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%: H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	To perform the pairwise comparisons simultaneously, a closed testing procedure was applied. When the hypothesis μ0.9 = μ0.6 = μSU was rejected, the 2 hypotheses of pairwise comparison were tested simultaneously both at significance level of 5%.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-150.22
	Confidence Interval	() 95%; -186.32 to -114.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%: H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	To perform the pairwise comparisons simultaneously, a closed testing procedure was applied. When the hypothesis μ0.9 = μ0.6 = μSU was rejected, the 2 hypotheses of pairwise comparison were tested simultaneously both at significance level of 5%.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-111.15
	Confidence Interval	() 95%; -147.61 to -74.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Postprandial Glucose AUC After 52 Weeks of Treatment
Description	Postprandial Glucose AUC measured 0-3 hours after a meal after 52 weeks of treatment
Time Frame	after 52 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
Measure Participants	78	83	68
Least Squares Mean (Standard Error) [mg/dL *h]	648.87 (16.09)	589.98 (16.17)	717.55 (17.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-127.57
	Confidence Interval	() 95%; -166.91 to -88.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-68.68
	Confidence Interval	() 95%; -108.91 to -28.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Mean PG in 7-point Plasma Glucose Profile After 24 Weeks of Treatment
Description	Plasma glucose (PG) profile measured after 24 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime.
Time Frame	after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
Measure Participants	80	82	80
Least Squares Mean (Standard Error) [mg/dL]	160.20 (4.44)	150.05 (4.56)	194.50 (4.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%: H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	To perform the pairwise comparisons simultaneously, a closed testing procedure was applied. When the hypothesis μ0.9 = μ0.6 = μSU was rejected, the 2 hypotheses of pairwise comparison were tested simultaneously both at significance level of 5%.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-44.45
	Confidence Interval	() 95%; -55.02 to -33.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%: H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	To perform the pairwise comparisons simultaneously, a closed testing procedure was applied. When the hypothesis μ0.9 = μ0.6 = μSU was rejected, the 2 hypotheses of pairwise comparison were tested simultaneously both at significance level of 5%.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-34.30
	Confidence Interval	() 95%; -45.06 to -23.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Mean PG in 7-point Plasma Glucose Profile After 52 Weeks of Treatment
Description	7-point plasma glucose (PG) profile measured after 52 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime.
Time Frame	after 52 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
Measure Participants	81	80	82
Least Squares Mean (Standard Error) [mg/dL]	171.42 (5.11)	159.58 (5.30)	205.92 (5.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-34.49
	Confidence Interval	() 95%; -46.77 to -22.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-46.34
	Confidence Interval	() 95%; -58.49 to -34.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Mean Postprandial PG Increment in 7-point Plasma Glucose Profile After 24 Weeks of Treatment
Description	Mean postprandial plasma glucose (PG) increment in 7-point plasma glucose profile, ie the mean of the difference of plasma glucose measured before and after a meal, after 24 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime.
Time Frame	after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
Measure Participants	81	82	82
Least Squares Mean (Standard Error) [mg/dL]	86.38 (4.65)	68.34 (4.78)	79.71 (4.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%: H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0433
	Comments	To perform the pairwise comparisons simultaneously, a closed testing procedure was applied. When the hypothesis μ0.9 = μ0.6 = μSU was rejected, the 2 hypotheses of pairwise comparison were tested simultaneously both at significance level of 5%.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-11.37
	Confidence Interval	() 95%; -22.40 to -0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%: H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2359
	Comments	To perform the pairwise comparisons simultaneously, a closed testing procedure was applied. When the hypothesis μ0.9 = μ0.6 = μSU was rejected, the 2 hypotheses of pairwise comparison were tested simultaneously both at significance level of 5%.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	6.67
	Confidence Interval	() 95%; -4.39 to 17.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Mean Postprandial PG Increment in 7-point Plasma Glucose Profile After 52 Weeks of Treatment
Description	Mean postprandial plasma glucose (PG) increment in 7-point plasma glucose profile, ie the mean of the difference of plasma glucose measured before and after a meal, after 52 weeks of treatment. The 7 time points during the day were: Before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, and at bedtime.
Time Frame	after 52 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
Measure Participants	82	80	85
Least Squares Mean (Standard Error) [mg/dL]	82.28 (4.81)	76.09 (5.00)	89.39 (4.86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-13.30
	Confidence Interval	() 95%; -24.69 to -1.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-7.11
	Confidence Interval	() 95%; -18.42 to 4.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Body Weight After 24 Weeks of Treatment
Time Frame	after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
Measure Participants	87	87	88
Least Squares Mean (Standard Error) [kg]	65.77 (0.23)	65.34 (0.24)	64.59 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%: H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0071
	Comments	To perform the pairwise comparisons simultaneously, a closed testing procedure was applied. When the hypothesis μ0.9 = μ0.6 = μSU was rejected, the 2 hypotheses of pairwise comparison were tested simultaneously both at significance level of 5%.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	0.75
	Confidence Interval	() 95%; 0.21 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	ANOVA model included treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate. Two null hypotheses were statistically tested, when the hypothesis μ0.9 = μ0.6 = μSU was rejected at a significance level of 5%: H10: μ0.9 = μSU, H11: μ0.9 ≠ μSU H20: μ0.6 = μSU, H21: μ0.6 ≠ μSU where μ0.6, μ0.9 and μSU are population mean after 24-week treatment for 0.6 mg+SU, 0.9 mg+SU and SU mono, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	To perform the pairwise comparisons simultaneously, a closed testing procedure was applied. When the hypothesis μ0.9 = μ0.6 = μSU was rejected, the 2 hypotheses of pairwise comparison were tested simultaneously both at significance level of 5%.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	1.18
	Confidence Interval	() 95%; 0.63 to 1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Body Weight After 52 Weeks of Treatment
Time Frame	after 52 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) using LOCF (Last Observation Carried Forward) is all subjects who received at least one dose of study drug and have valid measurements both at baseline and at least one time point after baseline.

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
Measure Participants	87	87	88
Least Squares Mean (Standard Error) [kg]	65.96 (0.26)	65.87 (0.27)	64.83 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	1.04
	Confidence Interval	() 95%; 0.42 to 1.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	95% confidence interval for the mean difference (each liraglutide - SU monotherapy) was calculated under an analysis of variance (ANOVA) model with treatment group and pre-trial SU as fixed effects and corresponding baseline value as a covariate, and no statistical testing was performed
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	1.13
	Confidence Interval	() 95%; 0.51 to 1.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Hypoglycaemic Episodes
Description	Hypoglycaemic episodes measured over 52 weeks of treatment. Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.
Time Frame	over 52 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consists of all subjects who received at least one dose of study drug.

Arm/Group Title	0.6 mg + SU	0.9 mg + SU	SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment	Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
Measure Participants	88	88	88
All hypoglycaemic episodes	3.131	3.715	2.990
Major	0.0000	0.0000	0.0000
Minor	1.438	1.365	1.285
Symptoms only	1.693	2.350	1.705

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	The relative risk for 'All hypoglycaemic episodes' and 95% confidence interval are based on a generalised linear negative-binomial model, which included treatment group as a fixed effect and log of exposure time as an offset variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	1.59
	Confidence Interval	() 95%; 0.86 to 2.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	The relative risk for 'Minor episodes' and 95% confidence interval are based on a generalised linear negative-binomial model, which included treatment group as a fixed effect and log of exposure time as an offset variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	1.18
	Confidence Interval	() 95%; 0.56 to 2.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	0.9 mg + SU, SU Mono
	Comments	The relative risk for 'Symptoms only' and 95% confidence interval are based on a generalised linear negative-binomial model, which included treatment group as a fixed effect and log of exposure time as an offset variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	1.80
	Confidence Interval	() 95%; 0.92 to 3.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	The relative risk for 'All hypoglycaemic episodes' and 95% confidence interval are based on a generalised linear negative-binomial model, which included treatment group as a fixed effect and log of exposure time as an offset variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	1.62
	Confidence Interval	() 95%; 0.85 to 3.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	The relative risk for 'Minor episodes' and 95% confidence interval are based on a generalised linear negative-binomial model, which included treatment group as a fixed effect and log of exposure time as an offset variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	1.48
	Confidence Interval	() 95%; 0.69 to 3.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	0.6 mg + SU, SU Mono
	Comments	The relative risk for 'Symptoms only episodes' and 95% confidence interval are based on a generalised linear negative-binomial model, which included treatment group as a fixed effect and log of exposure time as an offset variable.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	1.45
	Confidence Interval	() 95%; 0.72 to 2.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events were collected in a time span over 52 weeks.
Adverse Event Reporting Description	The safety analysis population consists of all subjects exposed to study drug (Full Analysis Set, FAS).
Arm/Group Title	0.6 mg + SU		0.9 mg + SU		SU Mono
Arm/Group Description	Liraglutide 0.6 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment		Liraglutide 0.9 mg/day in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment		Liraglutide placebo (0.6 mg/day or 0.9 mg/day) in addition to subject's own sulphonylurea (glibenclamide, gliclazide or glimepiride) treatment
All Cause Mortality
	0.6 mg + SU		0.9 mg + SU		SU Mono
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	0.6 mg + SU		0.9 mg + SU		SU Mono
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/88 (4.5%)		3/88 (3.4%)		5/88 (5.7%)
Ear and labyrinth disorders
Sudden hearing loss	1/88 (1.1%)	1	0/88 (0%)	0	0/88 (0%)	0
Gastrointestinal disorders
Colitis ischaemic	0/88 (0%)	0	1/88 (1.1%)	1	0/88 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/88 (0%)	0	0/88 (0%)	0	1/88 (1.1%)	1
Infections and infestations
Bursitis infective	0/88 (0%)	0	1/88 (1.1%)	1	0/88 (0%)	0
Pneumonia	1/88 (1.1%)	1	0/88 (0%)	0	0/88 (0%)	0
Metabolism and nutrition disorders
Hyperglycaemia	0/88 (0%)	0	0/88 (0%)	0	1/88 (1.1%)	1
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis	1/88 (1.1%)	1	0/88 (0%)	0	0/88 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of skin	0/88 (0%)	0	0/88 (0%)	0	1/88 (1.1%)	1
Colon adenoma	0/88 (0%)	0	0/88 (0%)	0	1/88 (1.1%)	1
Oesophageal carcinoma	1/88 (1.1%)	1	0/88 (0%)	0	0/88 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epiglottic cyst	0/88 (0%)	0	1/88 (1.1%)	1	0/88 (0%)	0
Surgical and medical procedures
Cataract operation	0/88 (0%)	0	0/88 (0%)	0	1/88 (1.1%)	1
Other (Not Including Serious) Adverse Events
	0.6 mg + SU		0.9 mg + SU		SU Mono
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	68/88 (77.3%)		68/88 (77.3%)		59/88 (67%)
Eye disorders
Diabetic retinopathy	8/88 (9.1%)	8	11/88 (12.5%)	11	7/88 (8%)	7
Gastrointestinal disorders
Diarrhoea	7/88 (8%)	8	14/88 (15.9%)	17	7/88 (8%)	10
Constipation	8/88 (9.1%)	9	11/88 (12.5%)	12	4/88 (4.5%)	7
Dental caries	5/88 (5.7%)	5	5/88 (5.7%)	5	1/88 (1.1%)	1
Gastritis	3/88 (3.4%)	3	4/88 (4.5%)	4	8/88 (9.1%)	8
General disorders
Malaise	5/88 (5.7%)	6	1/88 (1.1%)	2	5/88 (5.7%)	6
Infections and infestations
Nasopharyngitis	37/88 (42%)	63	38/88 (43.2%)	51	35/88 (39.8%)	61
Injury, poisoning and procedural complications
Fall	5/88 (5.7%)	5	2/88 (2.3%)	3	2/88 (2.3%)	2
Investigations
Alanine aminotransferase increased	6/88 (6.8%)	7	2/88 (2.3%)	2	1/88 (1.1%)	1
Musculoskeletal and connective tissue disorders
Back pain	10/88 (11.4%)	10	7/88 (8%)	8	6/88 (6.8%)	6
Arthralgia	6/88 (6.8%)	6	3/88 (3.4%)	3	1/88 (1.1%)	1
Nervous system disorders
Dizziness	5/88 (5.7%)	7	6/88 (6.8%)	7	2/88 (2.3%)	2
Headache	10/88 (11.4%)	11	4/88 (4.5%)	4	8/88 (9.1%)	9
Hypoaesthesia	5/88 (5.7%)	6	0/88 (0%)	0	5/88 (5.7%)	5
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation	9/88 (10.2%)	12	6/88 (6.8%)	8	5/88 (5.7%)	5
Vascular disorders
Hypertension	5/88 (5.7%)	5	3/88 (3.4%)	3	4/88 (4.5%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Novo Nordisk acknowledges the Investigator's right to publish the entire results of the trial. Any such scientific paper, presentation, communication or other information concerning the investigation described in this protocol, must be submitted in writing to Novo Nordisk Trial Manager prior to submission for publication/presentation for comments. Comments will be given within four weeks from receipt of the manuscript.