Trial Outcomes & Findings for Efficacy and Safety of Liraglutide in Combination With Insulin Therapy Compared to Insulin Alone in Japanese Subjects With Type 2 Diabetes (NCT NCT01572740)
NCT ID: NCT01572740
Last Updated: 2018-02-07
Results Overview
Estimated mean change from baseline in HbA1c after 16 Weeks of treatment.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
257 participants
Primary outcome timeframe
Week 0, Week 16
Results posted on
2018-02-07
Participant Flow
This trial was conducted at 23 sites in Japan.
Subjects on pre-trial insulin (basal insulin \[intermediate acting human insulin, intermediate acting insulin analogue or long-acting insulin analogue\], premixed insulin or basal-bolus regimen) therapy for at least 12 weeks prior to screening.
Participant milestones
| Measure |
Lira + Insulin
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Overall Study
STARTED
|
127
|
130
|
|
Overall Study
COMPLETED
|
121
|
125
|
|
Overall Study
NOT COMPLETED
|
6
|
5
|
Reasons for withdrawal
| Measure |
Lira + Insulin
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
unclassified
|
4
|
3
|
Baseline Characteristics
Efficacy and Safety of Liraglutide in Combination With Insulin Therapy Compared to Insulin Alone in Japanese Subjects With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Lira + Insulin
n=127 Participants
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=130 Participants
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Total
n=257 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61.3 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
59.8 years
STANDARD_DEVIATION 11.3 • n=7 Participants
|
60.5 years
STANDARD_DEVIATION 11.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
58 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
113 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
69 Participants
n=5 Participants
|
75 Participants
n=7 Participants
|
144 Participants
n=5 Participants
|
|
Body Weight
|
67.7 kg
STANDARD_DEVIATION 15.2 • n=5 Participants
|
65.9 kg
STANDARD_DEVIATION 13.0 • n=7 Participants
|
66.8 kg
STANDARD_DEVIATION 14.1 • n=5 Participants
|
|
Fasting Plasma Glucose (FPG)
|
8.51 mmol/L
STANDARD_DEVIATION 2.42 • n=5 Participants
|
8.79 mmol/L
STANDARD_DEVIATION 2.51 • n=7 Participants
|
8.65 mmol/L
STANDARD_DEVIATION 2.47 • n=5 Participants
|
|
Glycosylated Haemoglobin (HbA1c)
|
8.8 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.9 • n=5 Participants
|
8.8 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.9 • n=7 Participants
|
8.8 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.9 • n=5 Participants
|
PRIMARY outcome
Timeframe: Week 0, Week 16Population: Full analysis set (FAS) included all randomised subjects who received at least one dose of trial products. Missing data were imputed using last observation carried forward (LOCF). 1 subject in the placebo group did not contribute to the statistical analysis at Week 16 as subject was withdrawn from the trial before sampling for any efficacy data.
Estimated mean change from baseline in HbA1c after 16 Weeks of treatment.
Outcome measures
| Measure |
Lira + Insulin
n=127 Participants
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=129 Participants
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 16
|
-1.73 percentage of glycosylated haemoglobin
Standard Error 0.06
|
-0.43 percentage of glycosylated haemoglobin
Standard Error 0.06
|
SECONDARY outcome
Timeframe: Week 0, Week 36Population: Full analysis set (FAS) included all randomised subjects who received at least one dose of trial products. Missing data were imputed using last observation carried forward (LOCF). 1 subject in the placebo group did not contribute to the statistical analysis at Week 36 as subject was withdrawn from the trial before sampling for any efficacy data.
Estimated mean change from baseline in HbA1c after 36 Weeks of treatment
Outcome measures
| Measure |
Lira + Insulin
n=127 Participants
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=129 Participants
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 36
|
-1.68 percentage of glycosylated haemoglobin
Standard Error 0.06
|
-0.88 percentage of glycosylated haemoglobin
Standard Error 0.06
|
SECONDARY outcome
Timeframe: Week 0, Week 16Population: Full analysis set (FAS) included all randomised subjects who received at least one dose of trial products. Missing data were imputed using last observation carried forward (LOCF). 1 subject in the placebo group did not contribute to the statistical analysis at Week 16 as subject was withdrawn from the trial before sampling for any efficacy data.
Estimated mean change from baseline in FPG after 16 Weeks of treatment.
Outcome measures
| Measure |
Lira + Insulin
n=127 Participants
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=129 Participants
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 16
|
-1.31 mmol/L
Standard Error 0.17
|
-0.48 mmol/L
Standard Error 0.17
|
SECONDARY outcome
Timeframe: Week 0, Week 36Population: Full analysis set (FAS) included all randomised subjects who received at least one dose of trial products. Missing data were imputed using last observation carried forward (LOCF). 1 subject in the placebo group did not contribute to the statistical analysis at Week 36 as subject was withdrawn from the trial before sampling for any efficacy data.
Estimated mean change from baseline in FPG after 36 Weeks of treatment.
Outcome measures
| Measure |
Lira + Insulin
n=127 Participants
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=129 Participants
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 36
|
-1.55 mmol/L
Standard Error 0.16
|
-1.29 mmol/L
Standard Error 0.16
|
SECONDARY outcome
Timeframe: Week 0, Week 16Population: Full analysis set (FAS) included all randomised subjects who received at least one dose of trial products. Missing data were imputed using last observation carried forward (LOCF). 9 subjects did not contribute to the statistical analysis at Week 16 due to missing data.
Estimated mean change from baseline in mean PG of 7-point profile (7-points 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) after 16 Weeks of treatment.
Outcome measures
| Measure |
Lira + Insulin
n=124 Participants
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=124 Participants
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Change in Mean Plasma Glucose (PG) of 7-Point Profile From Baseline to Week 16
|
-2.41 mmol/L
Standard Error 0.18
|
-0.53 mmol/L
Standard Error 0.18
|
SECONDARY outcome
Timeframe: Week 0, Week 36Population: Full analysis set (FAS) included all randomised subjects who received at least one dose of trial products. Missing data were imputed using last observation carried forward (LOCF). 8 subjects did not contribute to the statistical analysis at Week 36 due to missing data.
Estimated mean change from baseline in mean PG of 7-point profile (7-points 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) after 36 Weeks of treatment.
Outcome measures
| Measure |
Lira + Insulin
n=124 Participants
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=125 Participants
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Change in Mean Plasma Glucose (PG) of 7-Point Profile From Baseline to Week 36
|
-2.65 mmol/L
Standard Error 0.16
|
-1.37 mmol/L
Standard Error 0.16
|
SECONDARY outcome
Timeframe: Week 0, Week 16Population: Full analysis set (FAS) included all randomised subjects who received at least one dose of trial products. Missing data were imputed using last observation carried forward (LOCF). 9 subjects did not contribute to the statistical analysis at Week 16 due to missing data.
Estimated mean change from baseline in mean prandial PG increment of 7-point profile (7-points 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) after 16 Weeks of treatment.
Outcome measures
| Measure |
Lira + Insulin
n=124 Participants
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=124 Participants
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Change in Mean Prandial PG Increment of 7-Point Profile From Baseline to Week 16
|
-1.34 mmol/L
Standard Error 0.17
|
-0.61 mmol/L
Standard Error 0.17
|
SECONDARY outcome
Timeframe: Week 0, Week 36Population: Full analysis set (FAS) included all randomised subjects who received at least one dose of trial products. Missing data were imputed using last observation carried forward (LOCF). 13 subjects did not contribute to the statistical analysis at Week 36 due to missing data.
Estimated mean change from baseline in mean prandial PG increment of 7-point profile (7-points 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) after 36 Weeks of treatment.
Outcome measures
| Measure |
Lira + Insulin
n=122 Participants
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=122 Participants
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Change in Mean Prandial PG Increment of 7-Point Profile From Baseline to Week 36
|
-1.34 mmol/L
Standard Error 0.21
|
-0.94 mmol/L
Standard Error 0.21
|
SECONDARY outcome
Timeframe: Week 0, Week 16Population: Full analysis set (FAS) included all randomised subjects who received at least one dose of trial products. Missing data were imputed using last observation carried forward (LOCF). 1 subject in the placebo group did not contribute to the statistical analysis at Week 16 as subject was withdrawn from the trial before sampling for any efficacy data.
Estimated mean change in body weight after 16 Weeks of treatment
Outcome measures
| Measure |
Lira + Insulin
n=127 Participants
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=129 Participants
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Change in Body Weight From Baseline to Week 16
|
-0.42 kg
Standard Error 0.14
|
-0.28 kg
Standard Error 0.14
|
SECONDARY outcome
Timeframe: Week 0, Week 36Population: Full analysis set (FAS) included all randomised subjects who received at least one dose of trial products. Missing data were imputed using last observation carried forward (LOCF). 1 subject in the placebo group did not contribute to the statistical analysis at Week 36 as subject was withdrawn from the trial before sampling for any efficacy data.
Estimated mean change in body weight after 36 Weeks of treatment
Outcome measures
| Measure |
Lira + Insulin
n=127 Participants
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=129 Participants
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Change in Body Weight From Baseline to Week 36
|
0.17 kg
Standard Error 0.20
|
0.52 kg
Standard Error 0.20
|
SECONDARY outcome
Timeframe: Week 0 to Week 36 (inclusive)Population: Safety analysis set includes all subjects who received at least one dose of the trial products.
An AE was defined as treatment emergent if the onset date was on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment.
Outcome measures
| Measure |
Lira + Insulin
n=127 Participants
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=130 Participants
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Number of Adverse Events (AEs)
Adverse Events
|
449 Events/100 years of patient exposure
|
350 Events/100 years of patient exposure
|
|
Number of Adverse Events (AEs)
Serious Adverse Events
|
8 Events/100 years of patient exposure
|
5 Events/100 years of patient exposure
|
|
Number of Adverse Events (AEs)
Severe Adverse Events
|
5 Events/100 years of patient exposure
|
1 Events/100 years of patient exposure
|
|
Number of Adverse Events (AEs)
Moderate Adverse Events
|
8 Events/100 years of patient exposure
|
14 Events/100 years of patient exposure
|
|
Number of Adverse Events (AEs)
Mild Adverse Events
|
436 Events/100 years of patient exposure
|
335 Events/100 years of patient exposure
|
SECONDARY outcome
Timeframe: Week 0 to week 36 (inclusive)Population: Safety analysis set includes all subjects who received at least one dose of the trial products.
A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and until the last day on randomised treatment. Confirmed hypoglycaemic episode was defined as hypoglycaemic episodes categorised to severe and/or minor hypoglycaemic episodes. Confirmed hypoglycaemia: subject unable to treat himself/herself and/or have a recorded PG \< 3.1 mmol/L (56 mg/dL). Minor: PG \< 3.1 mmol/L (56 mg/dL).
Outcome measures
| Measure |
Lira + Insulin
n=127 Participants
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=130 Participants
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Number of Confirmed Hypoglycaemic Episodes
|
146 Episodes/100 years of patient exposure
|
187 Episodes/100 years of patient exposure
|
Adverse Events
Lira + Insulin
Serious events: 6 serious events
Other events: 93 other events
Deaths: 0 deaths
Placebo + Insulin
Serious events: 4 serious events
Other events: 69 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lira + Insulin
n=127 participants at risk
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=130 participants at risk
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/127 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
0.77%
1/130 • Number of events 1 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Cardiac disorders
Angina pectoris
|
0.79%
1/127 • Number of events 1 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
0.00%
0/130 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Eye disorders
Cataract
|
0.79%
1/127 • Number of events 1 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
0.00%
0/130 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Eye disorders
Macular fibrosis
|
0.79%
1/127 • Number of events 1 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
0.00%
0/130 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/127 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
0.77%
1/130 • Number of events 1 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.79%
1/127 • Number of events 1 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
0.00%
0/130 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Nervous system disorders
Brain stem thrombosis
|
0.79%
1/127 • Number of events 1 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
0.00%
0/130 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Nervous system disorders
Carotid artery stenosis
|
0.79%
1/127 • Number of events 1 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
0.00%
0/130 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/127 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
0.77%
1/130 • Number of events 1 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.00%
0/127 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
0.77%
1/130 • Number of events 1 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Vascular disorders
Hypertension
|
0.79%
1/127 • Number of events 1 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
0.00%
0/130 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
Other adverse events
| Measure |
Lira + Insulin
n=127 participants at risk
Liraglutide was administered subcutaneously (s.c., under the skin) once daily (OD) for 36 weeks combined with insulin therapy. The starting dose of the liraglutide was 0.3 mg (50 μL)/day; dose was escalated to 0.6 mg (100 μL)/day and 0.9 mg (150 μL)/day during first 2 weeks; dose was maintained at 0.9 mg (150 μL)/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
Placebo + Insulin
n=130 participants at risk
Liraglutide placebo was administered subcutaneously (s.c., under the skin) OD for 36 weeks combined with insulin therapy. The starting dose of the placebo was 50 μL/day; dose was escalated to100 μL/day and 150 μL/day during first 2 weeks; dose was maintained at 150 μL/day for subsequent 34 weeks.
All subjects continued their pre-trial insulin therapy (basal: once daily \[OD\] or twice daily \[BID\], premixed: OD or BID or basal-bolus regimen \[basal: OD or BID and bolus: three times a day\]). Insulin dose was not changed for any subject for the first 16 weeks and for the subsequent 20 weeks, insulin dose was individually adjusted.
|
|---|---|---|
|
Eye disorders
Diabetic retinopathy
|
7.1%
9/127 • Number of events 9 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
10.0%
13/130 • Number of events 16 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Gastrointestinal disorders
Constipation
|
11.8%
15/127 • Number of events 16 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
1.5%
2/130 • Number of events 2 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Gastrointestinal disorders
Diarrhoea
|
11.8%
15/127 • Number of events 17 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
3.1%
4/130 • Number of events 4 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Gastrointestinal disorders
Dyspepsia
|
5.5%
7/127 • Number of events 9 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
0.00%
0/130 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Gastrointestinal disorders
Nausea
|
11.0%
14/127 • Number of events 16 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
5.4%
7/130 • Number of events 9 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Infections and infestations
Gastroenteritis
|
3.1%
4/127 • Number of events 7 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
5.4%
7/130 • Number of events 7 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Infections and infestations
Nasopharyngitis
|
43.3%
55/127 • Number of events 74 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
30.8%
40/130 • Number of events 60 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.7%
6/127 • Number of events 6 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
5.4%
7/130 • Number of events 7 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Nervous system disorders
Headache
|
6.3%
8/127 • Number of events 10 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
4.6%
6/130 • Number of events 6 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
|
Vascular disorders
Hypertension
|
6.3%
8/127 • Number of events 8 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
4.6%
6/130 • Number of events 6 • Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.
Safety analysis set includes all subjects who received at least one dose of the trial products.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Novo Nordisk maintains the right to be informed of any investigator plans for publication and to review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Any such communication must be submitted in writing to the Novo Nordisk Trial Manager prior to submission for comments. Comments will be given within four weeks from receipt of the planned communication.
- Publication restrictions are in place
Restriction type: OTHER