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Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects With Co-morbidities: SCALE™ - Obesity and Pre-diabetes

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ClinicalTrials.gov Identifier: NCT01272219
Recruitment Status : Completed
First Posted : January 7, 2011
Results First Posted : February 9, 2015
Last Update Posted : January 19, 2018
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Metabolism and Nutrition Disorder
Obesity
Interventions Drug: liraglutide
Drug: placebo
Enrollment 3731

Recruitment Details The trial was conducted at 191 sites in 27 countries: Australia:4,Austria:3,Belgium:2, Brazil:5,Canada:11, Denmark:3,Finland:3, France:5, Germany:8,Hong Kong:1, Hungary:2, India:8, Ireland:1,Israel:7, Italy:7, Mexico:4, Netherlands:5, Norway:3, Poland:5, Russian:7, Serbia:2, South Africa:3, Spain:6, Switzerland:5,Turkey:4, UK:8, US:69.
Pre-assignment Details Subjects were stratified based on pre-diabetes status and BMI at screening. The Main Period table, below, reflects the stratification that should have occurred at baseline. The Re-randomized Period and Main + Extension Period tables reflect the actual distribution of subjects, factoring in an incorrect stratification of 43 subjects at screening.
Arm/Group Title Liraglutide 3.0 mg, no Pre-diabetes Liraglutide 3.0mg (week0-56)/Liraglutide 3.0mg (week56-68) Liraglutide 3.0mg (week0-56)/Liraglutide Placebo (week56-68) Liraglutide Placebo, no Pre-diabetes Liraglutide 3.0 mg, Pre-diabetes Liraglutide Placebo, Pre-diabetes
Hide Arm/Group Description Arm 1 (Arm 1A + Arm 1B): Subjects with no pre-diabetes at screening received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks followed by a re-randomisation (1:1 into liraglutide 3.0 mg or liraglutide placebo) period of 12 weeks (weeks 56-68) and then an off-drug follow-up period of 2 weeks. The total duration of this treatment arm from randomisation to follow-up was 70 weeks. Arm 1A: Subjects of Arm 1 (with no pre-diabetes at screening) receiving liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks were re-randomised (1:1 into liraglutide 3.0 mg or liraglutide placebo) to continue treatment with liraglutide 3.0 mg for the next 12 weeks (weeks 56-68), followed by a 2 weeks off-drug follow-up period. Arm 1B: Subjects of Arm 1 (with no pre-diabetes at screening) receiving liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks were re-randomised (1:1 into liraglutide 3.0 mg or liraglutide placebo) to receive liraglutide placebo for the next 12 weeks (weeks 56-68), followed by a 2 weeks off-drug follow-up period. Arm 2: Subjects with no pre-diabetes at screening received liraglutide placebo once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks and then continued with liraglutide placebo for additional 12 weeks (weeks 56-68), followed by a 2 weeks off-drug follow-up period. The total duration of this treatment arm from randomisation to follow-up was 70 weeks. Arm 3: Subjects with pre-diabetes at screening received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for initial 56 weeks then continued treatment till 160 weeks, followed by an off-drug, observational follow-up period of 12 weeks. The total duration of this treatment arm from randomisation to follow-up was 172 weeks. Arm 4: Subjects with pre-diabetes at screening received liraglutide placebo once daily (OD) subcutaneously (s.c. injection, under the skin) for initial 56 weeks then continued treatment till 160 weeks, followed by an off-drug, observational follow-up period of 12 weeks. The total duration of this treatment arm from randomisation to follow-up was 172 weeks.
Period Title: Main Period: Week 0 to Week 56
Started 959 0 [1] 0 [1] 487 1528 757
Exposed 957 0 0 487 1524 755
Completed 679 0 0 296 1110 505
Not Completed 280 0 0 191 418 252
Reason Not Completed
Adverse Event             86             0             0             16             152             29
Lack of Efficacy             11             0             0             14             12             22
Protocol Violation             25             0             0             18             40             20
Withdrawal criteria             122             0             0             114             172             147
Unclassified             36             0             0             29             42             34
[1]
This arm is not considered for main period as these subjects belong to re-randomised period
Period Title: Re-randomised Period: Week 56 to Week 68
Started 0 [1] 351 [2] 350 [2] 304 [2] 0 [1] 0 [1]
Completed 0 342 343 289 0 0
Not Completed 0 9 7 15 0 0
Reason Not Completed
Adverse Event             0             1             1             2             0             0
Lack of Efficacy             0             0             0             1             0             0
Protocol Violation             0             1             0             3             0             0
Withdrawal criteria             0             6             4             7             0             0
Unclassified             0             1             2             2             0             0
[1]
This arm is not considered for re-randomised period as these subjects belong to main period
[2]
Incorrect stratification: In this period, overall 37 pre-diabetic subjects were included by error.
Period Title: Main + Extension Period: Week 0-172
Started 0 [1] 0 [2] 0 [2] 0 [3] 1505 [4] 749 [4]
Exposed 0 0 0 0 1501 747
Completed 0 0 0 0 783 327
Not Completed 0 0 0 0 722 422
Reason Not Completed
Adverse Event             0             0             0             0             191             43
Lack of Efficacy             0             0             0             0             29             36
Protocol Violation             0             0             0             0             76             36
Withdrawal criteria             0             0             0             0             364             256
Missing reason             0             0             0             0             1             0
Unclassified             0             0             0             0             61             51
[1]
This arm is not considered for this period as these subjects belong to main period
[2]
This arm is not considered for this period as these subjects belong to re-randomised period
[3]
This arm is not considered for this period as these subjects belong to main and re-randomised period
[4]
Incorrect stratification: In this period, overall 6 subjects with no pre-diabetes included by error.
Arm/Group Title Liraglutide 3.0 mg, no Pre-diabetes Liraglutide Placebo, no Pre-diabetes Liraglutide 3.0 mg, Pre-diabetes Liraglutide Placebo, Pre-diabetes Total
Hide Arm/Group Description Arm 1 (Arm 1A + Arm 1B): Subjects with no pre-diabetes at screening received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks followed by a re-randomisation (1:1 into liraglutide 3.0 mg or liraglutide placebo) period of 12 weeks (weeks 56-68) and then an off-drug follow-up period of 2 weeks. The total duration of this treatment arm from randomisation to follow-up was 70 weeks. Arm 2: Subjects with no pre-diabetes at screening received liraglutide placebo once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks and then continued with liraglutide placebo for additional 12 weeks (weeks 56-68), followed by a 2 weeks off-drug follow-up period. The total duration of this treatment arm from randomisation to follow-up was 70 weeks. Arm 3: Subjects with pre-diabetes at screening received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for initial 56 weeks then continued treatment till 160 weeks, followed by an off-drug, observational follow-up period of 12 weeks. The total duration of this treatment arm from randomisation to follow-up was 172 weeks. Arm 4: Subjects with pre-diabetes at screening received liraglutide placebo once daily (OD) subcutaneously (s.c. injection, under the skin) for initial 56 weeks then continued treatment till 160 weeks, followed by an off-drug, observational follow-up period of 12 weeks. The total duration of this treatment arm from randomisation to follow-up was 172 weeks. Total of all reporting groups
Overall Number of Baseline Participants 959 487 1528 757 3731
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 959 participants 487 participants 1528 participants 757 participants 3731 participants
41.6  (11.7) 41.5  (11.5) 47.4  (11.8) 47.2  (11.8) 45.1  (12.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 959 participants 487 participants 1528 participants 757 participants 3731 participants
Female
801
  83.5%
390
  80.1%
1156
  75.7%
581
  76.8%
2928
  78.5%
Male
158
  16.5%
97
  19.9%
372
  24.3%
176
  23.2%
803
  21.5%
Fasting Body Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 959 participants 487 participants 1528 participants 757 participants 3731 participants
104.0  (20.1) 103.6  (21.2) 107.6  (21.8) 107.9  (21.8) 106.2  (21.4)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 959 participants 487 participants 1528 participants 757 participants 3731 participants
37.5  (6.2) 37.4  (6.2) 38.8  (6.4) 39.0  (6.3) 38.3  (6.4)
Glycosylated Haemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percentage of glycosylated haemoglobin
Number Analyzed 959 participants 487 participants 1528 participants 757 participants 3731 participants
5.3  (0.3) 5.3  (0.3) 5.8  (0.3) 5.7  (0.3) 5.6  (0.4)
Fasting Plasma Glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 959 participants 487 participants 1528 participants 757 participants 3731 participants
5.0  (0.4) 5.1  (0.5) 5.5  (0.6) 5.5  (0.5) 5.3  (0.6)
1.Primary Outcome
Title Change From Baseline in Fasting Body Weight
Hide Description The observed mean change from baseline in fasting body weight (%) after 56-weeks of treatment (main treatment period).
Time Frame Week 0, Week 56
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) included all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and who provided at least one post-baseline efficacy value. Missing data were imputed using last observation carried forward (LOCF).
Arm/Group Title Liraglutide 3.0 mg (56-Week) Liraglutide Placebo (56-Week)
Hide Arm/Group Description:
Subjects belong to Arm 1 (with no pre-diabetes at screening) and Arm 3 (with pre-diabetes at screening), received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks, from randomisation.
Subjects belong to Arm 2 (with no pre-diabetes at screening) and Arm 4 (with pre-diabetes at screening), received liraglutide Placebo, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks, from randomisation.
Overall Number of Participants Analyzed 2432 1220
Mean (Standard Deviation)
Unit of Measure: percent change
-7.98  (6.67) -2.62  (5.74)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liraglutide 3.0 mg (56-Week), Liraglutide Placebo (56-Week)
Comments Null-hypothesis: no treatment difference between treatment arms, i.e. liraglutide 3.0 mg and liraglutide placebo. Liraglutide 3.0 mg was considered superior to placebo in inducing and maintaining weight loss, if the estimated treatment effect (liraglutide 3.0 mg – liraglutide placebo) was statistically significantly smaller than zero.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated mean difference
Estimated Value -5.39
Confidence Interval (2-Sided) 95%
-5.82 to -4.95
Estimation Comments ANCOVA model with treatment, country, sex, pre-diabetes status at screening, baseline BMI stratum and an interaction between pre-diabetes status at screening and BMI stratum as fixed factors, and the baseline value as covariate.
2.Primary Outcome
Title Proportion of Subjects Losing at Least 5% of Baseline Fasting Body Weight.
Hide Description Percentage of subjects losing at least 5% of baseline fasting body weight after 56-weeks of treatment (main treatment period).
Time Frame At Week 56
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and who provided at least one post-baseline efficacy value. Missing data were imputed using LOCF.
Arm/Group Title Liraglutide 3.0 mg (56-Week) Liraglutide Placebo (56-Week)
Hide Arm/Group Description:
Subjects belong to Arm 1 (with no pre-diabetes at screening) and Arm 3 (with pre-diabetes at screening), received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks, from randomisation.
Subjects belong to Arm 2 (with no pre-diabetes at screening) and Arm 4 (with pre-diabetes at screening), received liraglutide Placebo, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks, from randomisation.
Overall Number of Participants Analyzed 2432 1220
Measure Type: Number
Unit of Measure: percentage of subjects
63.2 27.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liraglutide 3.0 mg (56-Week), Liraglutide Placebo (56-Week)
Comments Null-hypothesis: no treatment difference between treatment arms, i.e. liraglutide 3.0 mg and liraglutide placebo. Liraglutide 3.0 mg was considered superior to placebo in inducing and maintaining weight loss as assessed by the proportion of subjects losing ≥5% of their fasting baseline weight, if the estimated odds ratio (liraglutide 3.0 mg/liraglutide placebo) was statistically significantly greater than one.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.80
Confidence Interval (2-Sided) 95%
4.12 to 5.60
Estimation Comments The model included treatment, country, sex, pre-diabetes status at screening, BMI stratum and an interaction between pre-diabetes status at screening and BMI stratum as fixed factors, and the baseline value as covariate.
3.Primary Outcome
Title Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight
Hide Description Percentage of subjects losing >10% of baseline fasting body weight after 56-weeks of treatment (main treatment period).
Time Frame At 56 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS) included all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and who provided at least one post-baseline efficacy value. Missing data were imputed using LOCF.
Arm/Group Title Liraglutide 3.0 mg (56-Week) Liraglutide Placebo (56-Week)
Hide Arm/Group Description:
Subjects belong to Arm 1 (with no pre-diabetes at screening) and Arm 3 (with pre-diabetes at screening), received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks, from randomisation.
Subjects belong to Arm 2 (with no pre-diabetes at screening) and Arm 4 (with pre-diabetes at screening), received liraglutide Placebo, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks, from randomisation.
Overall Number of Participants Analyzed 2432 1220
Measure Type: Number
Unit of Measure: percentage of subjects
33.1 10.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liraglutide 3.0 mg (56-Week), Liraglutide Placebo (56-Week)
Comments Null-hypothesis: no treatment difference between treatment arms, i.e. liraglutide 3.0 mg and liraglutide placebo. Liraglutide 3.0 mg was considered superior to placebo in inducing and maintaining weight loss as assessed by the proportion of subjects losing >10% of their fasting baseline weight, if the estimated odds ratio (liraglutide 3.0 mg/liraglutide placebo) was statistically significantly greater than one.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.34
Confidence Interval (2-Sided) 95%
3.54 to 5.32
Estimation Comments The model included treatment, country, sex, pre-diabetes status at screening, BMI stratum and an interaction between pre-diabetes status at screening and BMI stratum as fixed factors, and the baseline value as covariate.
4.Primary Outcome
Title Proportion of Subjects With Onset of Type 2 Diabetes
Hide Description Proportion of subjects with onset of Type 2 diabetes mellitus (T2DM) at week 160 (main + extension treatment period) among subjects with pre-diabetes at baseline - evaluated as time to onset of T2DM. Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Time Frame At 160 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Subjects included in the FAS, who were stratified to 160-weeks of treatment; all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and with at least one post-baseline efficacy measurement, who were stratified to 160-weeks of treatment. Missing data were imputed using LOCF.
Arm/Group Title Liraglutide 3.0 mg (160-Week) Liraglutide Placebo (160-Week)
Hide Arm/Group Description:
Subjects belong to Arm 3 (with pre-diabetes at screening), received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 160 weeks, from randomisation.
Subjects belong to Arm 4 (with pre-diabetes at screening), received liraglutide placebo, once daily (OD) subcutaneously (s.c. injection, under the skin) for 160 weeks, from randomisation.
Overall Number of Participants Analyzed 1472 738
Measure Type: Number
Unit of Measure: Subject
26 46
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liraglutide 3.0 mg (160-Week), Liraglutide Placebo (160-Week)
Comments If the estimated time-to-event ratio (liraglutide 3.0 mg/ placebo), as assessed by the survival endpoint describing the time until onset of T2DM (‘diabetes-free time’), is statistically significantly >1, then liraglutide 3.0 mg was to be considered superior to placebo in delaying the onset of T2DM in subjects with pre-diabetes at baseline. Weibull model was used; included treatment, sex and BMI stratification factor as fixed factors and baseline FPG as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Weibull analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment estimate
Estimated Value 2.681
Confidence Interval (2-Sided) 95%
1.856 to 3.872
Estimation Comments The treatment estimate was the factor that the time to event is multiplied with for liraglutide 3.0 mg compared to placebo.
5.Secondary Outcome
Title Change From Baseline in Waist Circumference (cm)
Hide Description The observed mean change from baseline in waist circumference (cm) after 56-weeks of treatment (main treatment period).
Time Frame Week 0, Week 56
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and who provided at least one post-baseline efficacy value. Missing data were imputed using LOCF.
Arm/Group Title Liraglutide 3.0 mg (56-Week) Liraglutide Placebo (56-Week)
Hide Arm/Group Description:
Subjects belong to Arm 1 (with no pre-diabetes at screening) and Arm 3 (with pre-diabetes at screening), received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks, from randomisation.
Subjects belong to Arm 2 (with no pre-diabetes at screening) and Arm 4 (with pre-diabetes at screening), received liraglutide Placebo, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks, from randomisation.
Overall Number of Participants Analyzed 2437 1225
Mean (Standard Deviation)
Unit of Measure: cm
-8.19  (7.31) -3.94  (6.58)
6.Secondary Outcome
Title Change From Baseline in Waist Circumference (Subjects With Pre-diabetes at Baseline)
Hide Description The observed mean change from baseline in waist circumference (subjects with pre-diabetes at baseline) after 160 weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Time Frame Week 0, week 160
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Subjects included in the FAS, who were stratified to 160-weeks of treatment; all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and with at least one post-baseline efficacy measurement, who were stratified to 160-weeks of treatment. Missing data were imputed using LOCF.
Arm/Group Title Liraglutide 3.0 mg (160-Week) Liraglutide Placebo (160-Week)
Hide Arm/Group Description:
Subjects belong to Arm 3 (with pre-diabetes at screening), received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 160 weeks, from randomisation.
Subjects belong to Arm 4 (with pre-diabetes at screening), received liraglutide placebo, once daily (OD) subcutaneously (s.c. injection, under the skin) for 160 weeks, from randomisation.
Overall Number of Participants Analyzed 1472 738
Mean (Standard Deviation)
Unit of Measure: cm
-6.87  (8.28) -3.37  (7.47)
7.Secondary Outcome
Title Pre-diabetes Status After 56 Weeks of Treatment
Hide Description Observed percentage of subjects with pre-diabetes status after 56 weeks of treatment (main treatment period).
Time Frame Week 0, Week 56
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and who provided at least one post-baseline efficacy value. Missing data were imputed using LOCF.
Arm/Group Title Liraglutide 3.0 mg (56-Week) Liraglutide Placebo (56-Week)
Hide Arm/Group Description:
Subjects belong to Arm 1 (with no pre-diabetes at screening) and Arm 3 (with pre-diabetes at screening), received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks, from randomisation.
Subjects belong to Arm 2 (with no pre-diabetes at screening) and Arm 4 (with pre-diabetes at screening), received liraglutide Placebo, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks, from randomisation.
Overall Number of Participants Analyzed 2437 1225
Measure Type: Number
Unit of Measure: percentage of subjects
With No Pre-diabetes 78.3 50.9
With Pre-diabetes 20.6 46.1
With Transient Type 2 Diabetes 0.9 1.8
With Confirmed Type 2 Diabetes 0.2 1.1
8.Secondary Outcome
Title Pre-diabetes Status in Subject With Pre-diabetes at Baseline After 160 Weeks of Treatment
Hide Description Observed percentage of subjects (subjects with pre-diabetes at baseline) with pre-diabetes status after 160 weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Time Frame Week 0, week 160
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Subjects included in the FAS, who were stratified to 160-weeks of treatment; all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and with at least one post-baseline efficacy measurement, who were stratified to 160-weeks of treatment. Missing data were imputed using LOCF.
Arm/Group Title Liraglutide 3.0 mg (160-Week) Liraglutide Placebo (160-Week)
Hide Arm/Group Description:
Subjects belong to Arm 3 (with pre-diabetes at screening), received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 160 weeks, from randomisation.
Subjects belong to Arm 4 (with pre-diabetes at screening), received liraglutide placebo, once daily (OD) subcutaneously (s.c. injection, under the skin) for 160 weeks, from randomisation.
Overall Number of Participants Analyzed 1472 738
Measure Type: Number
Unit of Measure: percentage of subjects
With No Pre-diabetes 65.9 36.3
With Pre-diabetes 31.3 54.9
With Transient Type 2 Diabetes 1.1 2.6
With Confirmed Type 2 Diabetes 1.8 6.2
9.Secondary Outcome
Title Mean Change From Baseline in Fasting Body Weight (Subjects With Pre-diabetes at Baseline)
Hide Description The observed mean change from baseline in fasting body weight (subjects with pre-diabetes at baseline) after 160 weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Time Frame Week 0, week 160
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Subjects included in the FAS, who were stratified to 160-weeks of treatment; all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and with at least one post-baseline efficacy measurement, who were stratified to 160-weeks of treatment. Missing data were imputed using LOCF.
Arm/Group Title Liraglutide 3.0 mg (160-Week) Liraglutide Placebo (160-Week)
Hide Arm/Group Description:
Subjects belong to Arm 3 (with pre-diabetes at screening), received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 160 weeks, from randomisation.
Subjects belong to Arm 4 (with pre-diabetes at screening), received liraglutide placebo, once daily (OD) subcutaneously (s.c. injection, under the skin) for 160 weeks, from randomisation.
Overall Number of Participants Analyzed 1467 734
Mean (Standard Deviation)
Unit of Measure: percent change
-6.14  (7.34) -1.89  (6.27)
10.Secondary Outcome
Title Proportion of Subjects Losing at Least 5% and Proportion of Subjects Losing More Than 10% of Baseline Fasting Body Weight (Subjects With Pre-diabetes at Baseline)
Hide Description Percentage of subjects losing >=5% and percentage of subjects losing >10% of baseline fasting body weight (pre-diabetic subjects at baseline) after 160-weeks of treatment (main + extension treatment period). Subjects included in FAS, who were stratified to 160-weeks of treatment (i.e., excluding 37 subjects with pre-diabetes who entered the re-randomised period and including 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period).
Time Frame At 160 weeks
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Hide Analysis Population Description
Subjects included in the FAS, who were stratified to 160-weeks of treatment; all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and with at least one post-baseline efficacy measurement, who were stratified to 160-weeks of treatment. Missing data were imputed using LOCF.
Arm/Group Title Liraglutide 3.0 mg (160-Week) Liraglutide Placebo (160-Week)
Hide Arm/Group Description:
Subjects belong to Arm 3 (with pre-diabetes at screening), received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 160 weeks, from randomisation.
Subjects belong to Arm 4 (with pre-diabetes at screening), received liraglutide placebo, once daily (OD) subcutaneously (s.c. injection, under the skin) for 160 weeks, from randomisation.
Overall Number of Participants Analyzed 1467 734
Measure Type: Number
Unit of Measure: percentage of subjects
Losing >=5% of baseline body weight 49.6 23.7
Losing >10% of baseline body weight 24.8 9.9
11.Secondary Outcome
Title Change From Week 56 in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes)
Hide Description The observed mean change in fasting body weight (%) from week 56 to week 68 in re-randomised subjects (with no pre-diabetes at baseline) after 12-weeks of treatment (re-randomised treatment period).
Time Frame Week 56, Week 68
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Hide Analysis Population Description
The FAS included all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and who provided at least one post-baseline efficacy value. Missing data were imputed using LOCF.
Arm/Group Title Liraglutide 3.0mg (week0-56)/Liraglutide 3.0mg (week56-68) Liraglutide 3.0mg (week0-56)/Liraglutide Placebo (week56-68) Liraglutide Placebo, no Pre-diabetes
Hide Arm/Group Description:
Arm 1A: Subjects of Arm 1 (with no pre-diabetes at screening) receiving liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks were re-randomised (1:1 into liraglutide 3.0 mg or liraglutide placebo) to continue treatment with liraglutide 3.0 mg for the next 12 weeks (weeks 56-68), followed by a 2 weeks off-drug follow-up period.
Arm 1B: Subjects of Arm 1 (with no pre-diabetes at screening) receiving liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks were re-randomised (1:1 into liraglutide 3.0 mg or liraglutide placebo) to receive liraglutide placebo for the next 12 weeks (weeks 56-68), followed by a 2 weeks off-drug follow-up period.
Arm 2: Subjects with no pre-diabetes at screening received liraglutide placebo once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks and then continued with liraglutide placebo for additional 12 weeks (weeks 56-68), followed by a 2 weeks off-drug follow-up period. The total duration of this treatment arm from randomisation to follow-up was 70 weeks.
Overall Number of Participants Analyzed 349 346 299
Mean (Standard Deviation)
Unit of Measure: percent change
0.69  (2.58) 2.91  (3.01) 0.28  (2.39)
12.Secondary Outcome
Title Change From Baseline in Fasting Body Weight (%) (Re-randomised Subjects With No Pre-diabetes)
Hide Description The observed mean change from baseline in fasting body weight (%) in re-randomised subjects (with no pre-diabetes at baseline) after 68 weeks of treatment (main + re-randomised treatment period).
Time Frame Week 0, Week 68
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects who were exposed to at least one dose of trial product (liraglutide 3.0 mg or liraglutide placebo) and who provided at least one post-baseline efficacy value. Missing data were imputed using LOCF.
Arm/Group Title Liraglutide 3.0mg (week0-56)/Liraglutide 3.0mg (week56-68) Liraglutide 3.0mg (week0-56)/Liraglutide Placebo (week56-68) Liraglutide Placebo, no Pre-diabetes
Hide Arm/Group Description:
Arm 1A: Subjects of Arm 1 (with no pre-diabetes at screening) receiving liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks were re-randomised (1:1 into liraglutide 3.0 mg or liraglutide placebo) to continue treatment with liraglutide 3.0 mg for the next 12 weeks (weeks 56-68), followed by a 2 weeks off-drug follow-up period.
Arm 1B: Subjects of Arm 1 (with no pre-diabetes at screening) receiving liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks were re-randomised (1:1 into liraglutide 3.0 mg or liraglutide placebo) to receive liraglutide placebo for the next 12 weeks (weeks 56-68), followed by a 2 weeks off-drug follow-up period.
Arm 2: Subjects with no pre-diabetes at screening received liraglutide placebo once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks and then continued with liraglutide placebo for additional 12 weeks (weeks 56-68), followed by a 2 weeks off-drug follow-up period. The total duration of this treatment arm from randomisation to follow-up was 70 weeks.
Overall Number of Participants Analyzed 349 347 298
Mean (Standard Deviation)
Unit of Measure: percent change
-8.44  (7.23) -6.77  (7.67) -3.11  (7.52)
Time Frame For Arm 1 and Arm 2: week 0 to week 70 (68 weeks of treatment period + 2 weeks of follow-up). For Arm 3 and Arm 4: week 0 to week 172 (160 weeks of treatment period + 12 weeks of follow-up).
Adverse Event Reporting Description A total of 37 pre-diabetic subjects erroneously entered the re randomised period and their adverse events (AEs) were counted under the “pre-diabetic arms” (Arm 3 and Arm 4). A total of 6 subjects without pre-diabetes incorrectly stratified to the 160-week treatment period and their AEs were counted under the “no pre-diabetes arms” (Arm 1 and Arm 2)
 
Arm/Group Title Liraglutide 3.0 mg, Pre-diabetes Liraglutide Placebo, Pre-diabetes Liraglutide 3.0 mg, no Pre-diabetes Liraglutide Placebo, no Pre-diabetes
Hide Arm/Group Description Arm 3: Subjects with pre-diabetes at screening received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for initial 56 weeks then continued treatment till 160 weeks, followed by an off-drug, observational follow-up period of 12 weeks. The total duration of this treatment arm from randomisation to follow-up was 172 weeks. Arm 4: Subjects with pre-diabetes at screening received liraglutide placebo once daily (OD) subcutaneously (s.c. injection, under the skin) for initial 56 weeks then continued treatment till 160 weeks, followed by an off-drug, observational follow-up period of 12 weeks. The total duration of this treatment arm from randomisation to follow-up was 172 weeks. Arm 1 (Arm 1A + Arm 1B): Subjects with no pre-diabetes at screening received liraglutide 3.0 mg, once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks followed by a re-randomisation (1:1 into liraglutide 3.0 mg or liraglutide placebo) period of 12 weeks (weeks 56-68) and then an off-drug follow-up period of 2 weeks. The total duration of this treatment arm from randomisation to follow-up was 70 weeks. Arm 2: Subjects with no pre-diabetes at screening received liraglutide placebo once daily (OD) subcutaneously (s.c. injection, under the skin) for 56 weeks and then continued with liraglutide placebo for additional 12 weeks (weeks 56-68), followed by a 2 weeks off-drug follow-up period. The total duration of this treatment arm from randomisation to follow-up was 70 weeks.
All-Cause Mortality
Liraglutide 3.0 mg, Pre-diabetes Liraglutide Placebo, Pre-diabetes Liraglutide 3.0 mg, no Pre-diabetes Liraglutide Placebo, no Pre-diabetes
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Liraglutide 3.0 mg, Pre-diabetes Liraglutide Placebo, Pre-diabetes Liraglutide 3.0 mg, no Pre-diabetes Liraglutide Placebo, no Pre-diabetes
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   230/1524 (15.09%)      96/755 (12.72%)      59/957 (6.17%)      19/487 (3.90%)    
Blood and lymphatic system disorders         
Anaemia  1  1/1524 (0.07%)  1 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Bandaemia  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Hypercoagulation  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Leukocytosis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Cardiac disorders         
Acute coronary syndrome  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Angina unstable  1  1/1524 (0.07%)  1 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Aortic valve disease mixed  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Aortic valve stenosis  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Atrial fibrillation  1  4/1524 (0.26%)  4 2/755 (0.26%)  2 2/957 (0.21%)  2 0/487 (0.00%)  0
Atrial flutter  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Cardiac failure  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Cardiac failure chronic  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Cardiac tamponade  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Cardio-respiratory arrest  1  1/1524 (0.07%)  1 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Cardiomegaly  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Congestive cardiomyopathy  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Coronary artery disease  1  1/1524 (0.07%)  1 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Coronary artery stenosis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Hypertensive heart disease  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Left ventricular dysfunction  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Myocardial infarction  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Myocardial ischaemia  1  1/1524 (0.07%)  1 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Palpitations  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Pericarditis  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Supraventricular tachycardia  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Tachycardia  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Ventricular fibrillation  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Ventricular tachycardia  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Congenital, familial and genetic disorders         
Dermoid cyst  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Multiple endocrine adenomatosis Type I  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Ear and labyrinth disorders         
Vertigo  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Endocrine disorders         
Basedow  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Goitre  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Hyperparathyroidism primary  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Hyperthyroidism  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Toxic nodular goitre  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Eye disorders         
Cataract  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Retinal detachment  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Gastrointestinal disorders         
Abdominal hernia  1  3/1524 (0.20%)  4 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Abdominal pain  1  3/1524 (0.20%)  3 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Abdominal pain upper  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 1/487 (0.21%)  1
Anal fissure  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Anal fistula  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Barrett  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Caecitis  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Colitis  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Colitis ischaemic  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Colitis ulcerative  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Constipation  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Diarrhoea  1  0/1524 (0.00%)  0 2/755 (0.26%)  2 0/957 (0.00%)  0 0/487 (0.00%)  0
Diverticulum  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Faecal incontinence  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Gastric ulcer haemorrhage  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Gastritis  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Gastrointestinal haemorrhage  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Gastrooesophageal reflux disease  1  1/1524 (0.07%)  1 1/755 (0.13%)  2 0/957 (0.00%)  0 1/487 (0.21%)  1
Haemorrhoids  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Hiatus hernia  1  4/1524 (0.26%)  4 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Inguinal hernia  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Intestinal obstruction  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Intestinal perforation  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Intestinal prolapse  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Nausea  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Pancreatic cyst  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Pancreatitis  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Pancreatitis acute  1  3/1524 (0.20%)  3 1/755 (0.13%)  1 2/957 (0.21%)  2 0/487 (0.00%)  0
Rectal haemorrhage  1  1/1524 (0.07%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Umbilical hernia  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Umbilical hernia, obstructive  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Vomiting  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
General disorders         
Chest discomfort  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Chest pain  1  0/1524 (0.00%)  0 2/755 (0.26%)  2 1/957 (0.10%)  1 2/487 (0.41%)  2
Cyst  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Device dislocation  1  1/1524 (0.07%)  1 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Inflammation  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Medical device complication  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Metaplasia  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Non-cardiac chest pain  1  5/1524 (0.33%)  5 1/755 (0.13%)  1 0/957 (0.00%)  0 1/487 (0.21%)  1
Ulcer haemorrhage  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Hepatobiliary disorders         
Bile duct stone  1  3/1524 (0.20%)  3 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Biliary colic  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Cholecystitis  1  6/1524 (0.39%)  6 0/755 (0.00%)  0 2/957 (0.21%)  2 1/487 (0.21%)  1
Cholecystitis acute  1  9/1524 (0.59%)  9 1/755 (0.13%)  1 4/957 (0.42%)  4 0/487 (0.00%)  0
Cholecystitis chronic  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Cholelithiasis  1  22/1524 (1.44%)  23 6/755 (0.79%)  6 7/957 (0.73%)  7 1/487 (0.21%)  1
Gallbladder polyp  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Hepatic cyst  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Hepatic lesion  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Hepatitis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Hepatitis acute  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Immune system disorders         
Amyloidosis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Anaphylactic reaction  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Drug hypersensitivity  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 0/957 (0.00%)  0 1/487 (0.21%)  1
Hypersensitivity  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 0/957 (0.00%)  0 1/487 (0.21%)  1
Infections and infestations         
Abdominal wall infection  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Abscess neck  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Alveolar osteitis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Anal abscess  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Appendicitis  1  4/1524 (0.26%)  4 0/755 (0.00%)  0 0/957 (0.00%)  0 1/487 (0.21%)  1
Arthritis bacterial  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Arthritis infective  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Brain abscess  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Breast abscess  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Bronchitis  1  0/1524 (0.00%)  0 2/755 (0.26%)  2 0/957 (0.00%)  0 0/487 (0.00%)  0
Bronchopneumonia  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Campylobacter gastroenteritis  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Cellulitis  1  3/1524 (0.20%)  3 3/755 (0.40%)  3 0/957 (0.00%)  0 0/487 (0.00%)  0
Clostridium difficile colitis  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Cytomegalovirus infection  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Diverticulitis  1  3/1524 (0.20%)  3 1/755 (0.13%)  1 1/957 (0.10%)  1 0/487 (0.00%)  0
Empyema  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Erysipelas  1  3/1524 (0.20%)  3 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Gastroenteritis  1  4/1524 (0.26%)  4 0/755 (0.00%)  0 2/957 (0.21%)  2 1/487 (0.21%)  1
Gastroenteritis viral  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 2/957 (0.21%)  2 0/487 (0.00%)  0
Hepatitis A  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Incision site infection  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Lobar pneumonia  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Localised infection  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Meningitis  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Oophoritis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Osteomyelitis  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Pharyngotonsillitis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Pneumonia  1  2/1524 (0.13%)  2 1/755 (0.13%)  1 1/957 (0.10%)  1 0/487 (0.00%)  0
Post procedural infection  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Postoperative wound infection  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Pyelonephritis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Sepsis  1  1/1524 (0.07%)  1 2/755 (0.26%)  2 0/957 (0.00%)  0 0/487 (0.00%)  0
Septic shock  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Urinary tract infection  1  2/1524 (0.13%)  3 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Urosepsis  1  3/1524 (0.20%)  3 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Vulval abscess  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Injury, poisoning and procedural complications         
Accident  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Animal bite  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Ankle fracture  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Cartilage injury  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Clavicle fracture  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Drug dispensing error  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Fall  1  0/1524 (0.00%)  0 4/755 (0.53%)  4 0/957 (0.00%)  0 0/487 (0.00%)  0
Fibula fracture  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Hand fracture  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Humerus fracture  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Incisional hernia  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Joint dislocation  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Limb injury  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Limb traumatic amputation  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Meniscus lesion  1  0/1524 (0.00%)  0 2/755 (0.26%)  2 0/957 (0.00%)  0 0/487 (0.00%)  0
Muscle injury  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Muscle strain  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Post laminectomy syndrome  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Post procedural complication  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Post procedural haemorrhage  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Procedural pain  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Rib fracture  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 2/957 (0.21%)  2 0/487 (0.00%)  0
Road traffic accident  1  0/1524 (0.00%)  0 2/755 (0.26%)  2 0/957 (0.00%)  0 0/487 (0.00%)  0
Stab wound  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Tendon injury  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Tendon rupture  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Tibia fracture  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Upper limb fracture  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Ureteric injury  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Wound  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Wrong drug administered  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Investigations         
Alanine aminotransferase increased  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Amylase increased  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Blood creatine phosphokinase increased  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Catheterisation cardiac  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Lipase increased  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Weight decreased  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Weight increased  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Metabolism and nutrition disorders         
Central obesity  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Dehydration  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Hypocalcaemia  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Hypovolaemia  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Obesity  1  1/1524 (0.07%)  1 3/755 (0.40%)  3 0/957 (0.00%)  0 0/487 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/1524 (0.00%)  0 2/755 (0.26%)  2 2/957 (0.21%)  2 0/487 (0.00%)  0
Arthritis  1  1/1524 (0.07%)  1 2/755 (0.26%)  3 0/957 (0.00%)  0 0/487 (0.00%)  0
Back pain  1  4/1524 (0.26%)  4 3/755 (0.40%)  3 0/957 (0.00%)  0 1/487 (0.21%)  1
Bursitis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Cervical spinal stenosis  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Chondromalacia  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Chondropathy  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Dupuytren  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Intervertebral disc disorder  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Intervertebral disc protrusion  1  6/1524 (0.39%)  6 1/755 (0.13%)  1 1/957 (0.10%)  1 0/487 (0.00%)  0
Joint laxity  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Lumbar spinal stenosis  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Myalgia  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Neck pain  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 0/957 (0.00%)  0 1/487 (0.21%)  1
Osteoarthritis  1  12/1524 (0.79%)  14 5/755 (0.66%)  6 0/957 (0.00%)  0 0/487 (0.00%)  0
Osteonecrosis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Pain in jaw  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 0/957 (0.00%)  0 1/487 (0.21%)  1
Rheumatoid arthritis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Spinal osteoarthritis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Synovial cyst  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Adrenal adenoma  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Benign salivary gland neoplasm  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Bile duct cancer  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Breast cancer  1  5/1524 (0.33%)  5 0/755 (0.00%)  0 1/957 (0.10%)  1 2/487 (0.41%)  2
Breast cancer in situ  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Breast cancer metastatic  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Breast cancer stage III  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Carcinoid tumour of the small bowel  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Cholesteatoma  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Chronic myeloid leukaemia  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Colon adenoma  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Colon cancer  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Colon cancer metastatic  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Colon cancer stage 0  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Diffuse large B-cell lymphoma  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Dysplastic naevus  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Fibroadenoma of breast  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Haemangioma of bone  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Hepatic adenoma  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Laryngeal cancer  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Lentigo maligna  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Lipoma  1  1/1524 (0.07%)  4 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Lymphoma  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Mantle cell lymphoma stage I  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Melanocytic naevus  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Neoplasm skin  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Pancreatic carcinoma metastatic  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Prostate cancer  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Rectal cancer  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Seborrhoeic keratosis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Thyroid cancer  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Uterine leiomyoma  1  3/1524 (0.20%)  3 2/755 (0.26%)  2 0/957 (0.00%)  0 0/487 (0.00%)  0
Vaginal cancer  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Nervous system disorders         
Brain stem infarction  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Carotid artery aneurysm  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 0/957 (0.00%)  0 1/487 (0.21%)  1
Cerebrovascular accident  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Cervicobrachial syndrome  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Convulsion  1  1/1524 (0.07%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Dizziness  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Headache  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Hypoaesthesia  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 0/957 (0.00%)  0 1/487 (0.21%)  1
Intercostal neuralgia  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Intracranial pressure increased  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Ischaemic stroke  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Migraine  1  2/1524 (0.13%)  2 1/755 (0.13%)  1 2/957 (0.21%)  2 0/487 (0.00%)  0
Presyncope  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Spinal cord herniation  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Syncope  1  3/1524 (0.20%)  3 1/755 (0.13%)  1 1/957 (0.10%)  1 0/487 (0.00%)  0
Transient ischaemic attack  1  1/1524 (0.07%)  1 2/755 (0.26%)  3 0/957 (0.00%)  0 0/487 (0.00%)  0
VIIth nerve paralysis  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Pregnancy, puerperium and perinatal conditions         
Abortion missed  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Abortion spontaneous  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Abortion threatened  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Ectopic pregnancy  1  1/1524 (0.07%)  1 1/755 (0.13%)  1 0/957 (0.00%)  0 1/487 (0.21%)  1
Psychiatric disorders         
Anxiety  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 0/957 (0.00%)  0 1/487 (0.21%)  1
Depression  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 1/957 (0.10%)  1 0/487 (0.00%)  0
Suicidal ideation  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Suicide attempt  1  1/1524 (0.07%)  1 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Renal and urinary disorders         
Bladder prolapse  1  1/1524 (0.07%)  1 1/755 (0.13%)  1 0/957 (0.00%)  0 1/487 (0.21%)  1
Calculus ureteric  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
IgA nephropathy  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Nephrolithiasis  1  4/1524 (0.26%)  4 1/755 (0.13%)  1 1/957 (0.10%)  1 0/487 (0.00%)  0
Oliguria  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Renal colic  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Renal cyst  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Renal failure acute  1  2/1524 (0.13%)  2 2/755 (0.26%)  2 0/957 (0.00%)  0 0/487 (0.00%)  0
Renal impairment  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Renal infarct  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Stress urinary incontinence  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Urinary incontinence  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Reproductive system and breast disorders         
Adnexa uteri cyst  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Cervical dysplasia  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 1/487 (0.21%)  1
Dysmenorrhoea  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Endometrial disorder  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Endometrial hyperplasia  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Endometriosis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Menometrorrhagia  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Menorrhagia  1  3/1524 (0.20%)  3 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Metrorrhagia  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Ovarian cyst  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Pelvic adhesions  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Polymenorrhoea  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Rectocele  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 0/957 (0.00%)  0 1/487 (0.21%)  1
Uterine polyp  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Uterine prolapse  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Asthma  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Chronic obstructive pulmonary disease  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Dyspnoea  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Haemoptysis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Lung disorder  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Nasal septum deviation  1  3/1524 (0.20%)  3 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Nasal turbinate hypertrophy  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Pulmonary embolism  1  2/1524 (0.13%)  2 1/755 (0.13%)  1 1/957 (0.10%)  1 0/487 (0.00%)  0
Pulmonary fibrosis  1  0/1524 (0.00%)  0 0/755 (0.00%)  0 0/957 (0.00%)  0 1/487 (0.21%)  1
Sleep apnoea syndrome  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Skin and subcutaneous tissue disorders         
Angioedema  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Cutis laxa  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Eczema  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Excessive skin  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Panniculitis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Skin ulcer  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Social circumstances         
Miscarriage of partner  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Surgical and medical procedures         
Abdominoplasty  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Abortion induced  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Coronary arterial stent insertion  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Coronary revascularisation  1  3/1524 (0.20%)  4 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Gastrectomy  1  1/1524 (0.07%)  1 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Gastric bypass  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Heart transplant  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Hip arthroplasty  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Ligament operation  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Lipectomy  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Mammoplasty  1  1/1524 (0.07%)  1 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Obesity surgery  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Rectocele repair  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Vascular disorders         
Circulatory collapse  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Deep vein thrombosis  1  1/1524 (0.07%)  1 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Embolism venous  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Hypertension  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Hypotension  1  0/1524 (0.00%)  0 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Orthostatic hypotension  1  2/1524 (0.13%)  2 0/755 (0.00%)  0 0/957 (0.00%)  0 0/487 (0.00%)  0
Varicophlebitis  1  1/1524 (0.07%)  1 0/755 (0.00%)  0 1/957 (0.10%)  1 0/487 (0.00%)  0
Varicose vein  1  1/1524 (0.07%)  1 1/755 (0.13%)  1 0/957 (0.00%)  0 0/487 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Liraglutide 3.0 mg, Pre-diabetes Liraglutide Placebo, Pre-diabetes Liraglutide 3.0 mg, no Pre-diabetes Liraglutide Placebo, no Pre-diabetes
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1342/1524 (88.06%)      586/755 (77.62%)      843/957 (88.09%)      345/487 (70.84%)    
Gastrointestinal disorders         
Abdominal pain  1  112/1524 (7.35%)  150 37/755 (4.90%)  49 62/957 (6.48%)  79 19/487 (3.90%)  22
Abdominal pain upper  1  110/1524 (7.22%)  137 40/755 (5.30%)  49 63/957 (6.58%)  84 18/487 (3.70%)  20
Constipation  1  333/1524 (21.85%)  422 85/755 (11.26%)  100 203/957 (21.21%)  255 44/487 (9.03%)  52
Diarrhoea  1  388/1524 (25.46%)  626 107/755 (14.17%)  144 201/957 (21.00%)  308 46/487 (9.45%)  58
Dyspepsia  1  156/1524 (10.24%)  196 35/755 (4.64%)  40 102/957 (10.66%)  121 14/487 (2.87%)  16
Eructation  1  86/1524 (5.64%)  96 4/755 (0.53%)  4 38/957 (3.97%)  52 2/487 (0.41%)  2
Flatulence  1  81/1524 (5.31%)  94 22/755 (2.91%)  25 29/957 (3.03%)  35 15/487 (3.08%)  17
Gastrooesophageal reflux disease  1  101/1524 (6.63%)  112 18/755 (2.38%)  19 47/957 (4.91%)  50 8/487 (1.64%)  8
Nausea  1  622/1524 (40.81%)  974 128/755 (16.95%)  170 418/957 (43.68%)  616 78/487 (16.02%)  96
Vomiting  1  300/1524 (19.69%)  476 42/755 (5.56%)  55 172/957 (17.97%)  267 25/487 (5.13%)  29
General disorders         
Fatigue  1  154/1524 (10.10%)  190 58/755 (7.68%)  67 79/957 (8.25%)  89 27/487 (5.54%)  31
Injection site haematoma  1  91/1524 (5.97%)  102 61/755 (8.08%)  69 64/957 (6.69%)  68 42/487 (8.62%)  45
Oedema peripheral  1  53/1524 (3.48%)  60 47/755 (6.23%)  58 22/957 (2.30%)  25 6/487 (1.23%)  7
Infections and infestations         
Bronchitis  1  114/1524 (7.48%)  139 62/755 (8.21%)  80 35/957 (3.66%)  41 26/487 (5.34%)  27
Gastroenteritis  1  138/1524 (9.06%)  171 46/755 (6.09%)  53 48/957 (5.02%)  53 24/487 (4.93%)  32
Influenza  1  181/1524 (11.88%)  249 80/755 (10.60%)  123 65/957 (6.79%)  84 26/487 (5.34%)  37
Nasopharyngitis  1  404/1524 (26.51%)  764 210/755 (27.81%)  408 193/957 (20.17%)  290 110/487 (22.59%)  166
Sinusitis  1  129/1524 (8.46%)  174 65/755 (8.61%)  111 84/957 (8.78%)  99 35/487 (7.19%)  47
Upper respiratory tract infection  1  236/1524 (15.49%)  389 120/755 (15.89%)  213 101/957 (10.55%)  122 54/487 (11.09%)  68
Urinary tract infection  1  123/1524 (8.07%)  176 43/755 (5.70%)  62 48/957 (5.02%)  60 15/487 (3.08%)  19
Investigations         
Lipase increased  1  145/1524 (9.51%)  207 24/755 (3.18%)  26 35/957 (3.66%)  41 10/487 (2.05%)  10
Metabolism and nutrition disorders         
Decreased appetite  1  169/1524 (11.09%)  181 27/755 (3.58%)  28 102/957 (10.66%)  111 16/487 (3.29%)  17
Hypoglycaemia  1  295/1524 (19.36%)  637 35/755 (4.64%)  52 176/957 (18.39%)  302 29/487 (5.95%)  37
Musculoskeletal and connective tissue disorders         
Arthralgia  1  186/1524 (12.20%)  231 97/755 (12.85%)  134 38/957 (3.97%)  41 23/487 (4.72%)  29
Back pain  1  198/1524 (12.99%)  283 118/755 (15.63%)  159 77/957 (8.05%)  97 41/487 (8.42%)  50
Pain in extremity  1  108/1524 (7.09%)  127 54/755 (7.15%)  64 25/957 (2.61%)  27 22/487 (4.52%)  24
Nervous system disorders         
Dizziness  1  149/1524 (9.78%)  197 55/755 (7.28%)  73 67/957 (7.00%)  81 19/487 (3.90%)  20
Headache  1  273/1524 (17.91%)  432 124/755 (16.42%)  223 127/957 (13.27%)  178 58/487 (11.91%)  80
Respiratory, thoracic and mediastinal disorders         
Cough  1  112/1524 (7.35%)  133 60/755 (7.95%)  87 34/957 (3.55%)  35 22/487 (4.52%)  23
Oropharyngeal pain  1  74/1524 (4.86%)  81 44/755 (5.83%)  52 31/957 (3.24%)  34 21/487 (4.31%)  22
Vascular disorders         
Hypertension  1  74/1524 (4.86%)  86 48/755 (6.36%)  58 22/957 (2.30%)  23 13/487 (2.67%)  13
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 15.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
When the primary results are available, Novo Nordisk plans to discuss the interpretation of these with the principal Investigator, but reserves the right to release results that may impact Novo Nordisk financial expectations (e.g. a press release directly to the public or similar) without prior consultation with the remaining participating Investigators. Novo Nordisk reserves the right not to release data until specified milestones, e.g. a clinical trial report is available.
Results Point of Contact
Name/Title: Public Access to Clinical Trials
Organization: Novo Nordisk A/S
Publications of Results:
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01272219     History of Changes
Other Study ID Numbers: NN8022-1839
2008-001049-24 ( EudraCT Number )
U1111-1118-7871 ( Other Identifier: WHO )
First Submitted: January 6, 2011
First Posted: January 7, 2011
Results First Submitted: January 22, 2015
Results First Posted: February 9, 2015
Last Update Posted: January 19, 2018