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Effect of Albiglutide, When Added to Standard Blood Glucose Lowering Therapies, on Major Cardiovascular Events in Subjects With Type 2 Diabetes Mellitus

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ClinicalTrials.gov Identifier: NCT02465515
Recruitment Status : Completed
First Posted : June 8, 2015
Results First Posted : March 6, 2019
Last Update Posted : March 6, 2019
Sponsor:
Collaborator:
Duke Clinical Research Institute
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Diabetes Mellitus
Interventions Biological: Albiglutide 30 mg
Biological: Albiglutide 50 mg
Biological: Albiglutide matching placebo
Enrollment 9463
Recruitment Details This was a randomized, double-blind, parallel group, placebo-controlled study in participants with Type 2 diabetes having a previous history of cardiovascular disease and not having optimal glycemic control.
Pre-assignment Details A total of 10793 participants were screened of which 1330 failed screening and 9463 participants were randomized in a 1:1 ratio to receive either once weekly albiglutide or matching placebo subcutaneous injections. The study was conducted in 28 countries
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Period Title: Overall Study
Started 4732 4731
Completed 4578 4620
Not Completed 154 111
Reason Not Completed
Investigator site closed             4             5
Withdrawal by Subject             74             43
Physician Decision             8             12
Lost to Follow-up             68             51
Arm/Group Title Placebo Albiglutide Total
Hide Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.. Total of all reporting groups
Overall Number of Baseline Participants 4732 4731 9463
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4732 participants 4731 participants 9463 participants
64.2  (8.65) 64.1  (8.71) 64.1  (8.68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4732 participants 4731 participants 9463 participants
Female
1467
  31.0%
1427
  30.2%
2894
  30.6%
Male
3265
  69.0%
3304
  69.8%
6569
  69.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race, customized Number Analyzed 4732 participants 4731 participants 9463 participants
American Indian (Amer. Ind.) or Alaska Native
238
   5.0%
280
   5.9%
518
   5.5%
Central/South Asian Heritage (Her.)
27
   0.6%
25
   0.5%
52
   0.5%
Japanese Her./East Asian Her/South East Asian Her.
215
   4.5%
204
   4.3%
419
   4.4%
Black or African American (Amer.)
118
   2.5%
121
   2.6%
239
   2.5%
Native Hawaiian or Other Pacific Islander
2
   0.0%
3
   0.1%
5
   0.1%
White
4024
  85.0%
4006
  84.7%
8030
  84.9%
Amer Ind. or Alaska Native & Black or African Amer
1
   0.0%
3
   0.1%
4
   0.0%
Asian & Black or African Amer.
1
   0.0%
0
   0.0%
1
   0.0%
Asian & White
0
   0.0%
1
   0.0%
1
   0.0%
Black or African Amer. & White
81
   1.7%
67
   1.4%
148
   1.6%
Unknown
1
   0.0%
1
   0.0%
2
   0.0%
Amer. Ind. or Alaska Native & White
24
   0.5%
20
   0.4%
44
   0.5%
1.Primary Outcome
Title Time to First Occurrence of Major Adverse Cardiovascular Events (MACE) During Cardiovascular (CV) Follow-up Time Period
Hide Description Time to MACE defined as the time to first occurrence of Cardiovascular Endpoint Committee (CEC)-adjudicated MACE (CV death, myocardial infarction [MI] or stroke) was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. The analysis was performed on the Intent to Treat (ITT) Population which comprised of all randomized participants excluding participants who did not provide consent.
Time Frame Median of 1.65 person years for CV follow-up time period
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4732 4731
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 person years
5.87
(5.33 to 6.45)
4.57
(4.10 to 5.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was determined by testing the hypothesis that the observed hazard ratio is significantly different from the null margin of 1.3 (a one-sided p <0.025 for such a test with result in appropriate direction being equivalent to the upper 95% confidence limit for the hazard ratio being less than 1.3)
Statistical Test of Hypothesis P-Value <0.0001
Comments One-sided p-value based on Wald test of hazard ratio (HR) >=1.3 versus HR <1.3.
Method Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.68 to 0.90
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Two-sided p-value based on Wald test of HR=1 versus HR not equal to 1
Method Wald test
Comments [Not Specified]
2.Secondary Outcome
Title Time to First Occurrence of MACE or Urgent Revascularization for Unstable Angina
Hide Description Time to first occurrence of CEC-adjudicated MACE (CV death, MI or stroke) or urgent revascularization for unstable angina was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time Frame Median of 1.65 person years for CV follow-up time period
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4732 4731
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 person years
6.45
(5.88 to 7.06)
5.06
(4.56 to 5.60)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Two-sided p-value based on the Wald statistic.
Method Wald statistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.69 to 0.90
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
3.Secondary Outcome
Title Time to Adjudicated CV Death
Hide Description Time to adjudicated CV death was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time Frame Median of 1.65 person years for the CV follow-up time period
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4732 4731
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 person years
1.72
(1.44 to 2.04)
1.61
(1.33 to 1.92)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.578
Comments Two-sided p-value based on the Wald statistic
Method Wald statistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.73 to 1.19
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate
4.Secondary Outcome
Title Time to First Occurrence of Adjudicated MI
Hide Description Time to first occurrence of adjudicated MI was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time Frame Median of 1.65 person years for CV follow-up time period
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4732 4731
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 person years
3.26
(2.86 to 3.70)
2.43
(2.09 to 2.81)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments Two-sided p-value based on the Wald statistic.
Method Wald statistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.61 to 0.90
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
5.Secondary Outcome
Title Time to First Occurrence of Adjudicated Stroke
Hide Description Time to first occurrence of adjudicated stroke was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time Frame Median of 1.65 person years for CV follow-up time period
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4732 4731
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 person years
1.45
(1.19 to 1.74)
1.25
(1.01 to 1.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.300
Comments Two-sided p-value based on the Wald statistic.
Method Wald statistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.66 to 1.14
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
6.Secondary Outcome
Title Time to First Occurrence of Adjudicated CV Death or Hospitalization for Heart Failure (HF)
Hide Description Time to first occurrence of adjudicated CV death or hospitalization for HF was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time Frame Median of 1.65 person years for CV follow-up time period
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4732 4731
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 person years
2.92
(2.55 to 3.34)
2.49
(2.15 to 2.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.113
Comments Two-sided p-value based on the Wald statistic.
Method Wald statistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.70 to 1.04
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
7.Secondary Outcome
Title Time to Initiation of Insulin of More Than 3 Months Duration for Those Participants Not Treated With Insulin at Study Start
Hide Description Time to initiation of insulin of more than 3 months duration in participants not treated with insulin at study start was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the on-therapy and post-therapy AE time period. The analysis was performed on Non-Insulin Population which comprised of participants in the ITT Population who were not on insulin at Baseline.
Time Frame Up to 2.7 years
Hide Outcome Measure Data
Hide Analysis Population Description
Non-Insulin Population
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 1995 1871
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 person years
8.58
(7.56 to 9.70)
3.56
(2.92 to 4.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Two-sided p-value based on Wald test of HR=1 versus HR not equal to 1.
Method Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.33 to 0.53
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
8.Secondary Outcome
Title Time to Initiation of Prandial Insulin in Those Participants on Basal Insulin at Study Start
Hide Description Time to initiation of prandial insulin in those participants on basal insulin at study start was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the on-therapy and post-therapy AE time period. The analysis was performed on Basal Insulin Population which comprised of participants in the ITT Population who were on basal insulin but not on other insulin at Baseline (i.e., will not include a participant on a mixed insulin or on a prandial-only insulin).
Time Frame Up to 2.7 years
Hide Outcome Measure Data
Hide Analysis Population Description
Basal Insulin Population
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 1040 1028
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 person years
5.09
(4.06 to 6.31)
3.59
(2.73 to 4.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.043
Comments Two-sided p-value based on Wald test of HR=1 versus HR not equal to 1.
Method Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.51 to 0.99
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
9.Secondary Outcome
Title Percentage of Participants Achieving Composite Metabolic Endpoint
Hide Description Percentage of participants achieving composite metabolic endpoint defined as the percentage of participants achieving glycemic control (glycated hemoglobin [HbA1c] <=7% ) with no severe hypoglycemic incidents and weight gain < 5%. Final Assessment is the latest post-Baseline assessment of both HbA1c and weight.
Time Frame Months 8, 16, 24 and final assessment (up to 2.7 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with HbA1c and weight values at Baseline and at the specified visits were analyzed (represented by n=X in category titles)
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4732 4731
Measure Type: Number
Unit of Measure: Percentage of participants
Month 8, n=4127, 4195 Number Analyzed 4127 participants 4195 participants
15.4 32.2
Month 16, n=3026, 3118 Number Analyzed 3026 participants 3118 participants
16.5 28.7
Month 24, n=1119, 1173 Number Analyzed 1119 participants 1173 participants
17.8 28.6
Final assessment, n=4401, 4455 Number Analyzed 4401 participants 4455 participants
15.1 26.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value based on the covariate-adjusted extended Mantel-Haenszel test. Covariates include Baseline HbA1c (<8.0% versus >= 8.0%) and Baseline diabetes therapy (diet and exercise alone versus all other therapies).
Method Mantel Haenszel
Comments Month 8
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value based on the covariate-adjusted extended Mantel-Haenszel test. Covariates include Baseline HbA1c (<8.0% versus >= 8.0%) and Baseline diabetes therapy (diet and exercise alone versus all other therapies).
Method Mantel Haenszel
Comments Month 16
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value based on the covariate-adjusted extended Mantel-Haenszel test. Covariates include Baseline HbA1c (<8.0% versus >= 8.0%) and Baseline diabetes therapy (diet and exercise alone versus all other therapies).
Method Mantel Haenszel
Comments Month 24
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value based on the covariate-adjusted extended Mantel-Haenszel test. Covariates include Baseline HbA1c (<8.0% versus >= 8.0%) and Baseline diabetes therapy (diet and exercise alone versus all other therapies).
Method Mantel Haenszel
Comments Final assessment
10.Secondary Outcome
Title Time to First Occurrence of a Clinically Important Microvascular Event
Hide Description Clinically important microvascular events were defined as the following: need for renal transplant or dialysis, new diabetes-related blindness, and procedures (laser photocoagulation or anti-vascular endothelial growth factor treatment or vitrectomy for diabetic retinopathy/eye disease). Time to first occurrence of a clinically important microvascular event was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the on-therapy and post-therapy AE time period.
Time Frame Up to 2.7 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4732 4731
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 person years
0.69
(0.52 to 0.90)
0.46
(0.32 to 0.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.055
Comments Two-sided p-value based on Wald test of HR=1 versus HR not equal to 1
Method Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.43 to 1.01
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
11.Secondary Outcome
Title Change From Baseline in HbA1c
Hide Description Change from Baseline in HbA1c was analyzed using mixed model repeated measures (MMRM) including observed case data (does not impute any missing data). Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value. Change from Baseline in HbA1c using Baseline data from Local or Central Laboratory, and post-Baseline Central Laboratory data is presented.
Time Frame Baseline and Months 8 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with value at Baseline and at the specified visit is presented (represented by n=X in category titles)
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4732 4731
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of HbA1c
Month 8, n=4211, 4289 Number Analyzed 4211 participants 4289 participants
-0.28  (0.020) -0.92  (0.019)
Month 16, n=3066, 3163 Number Analyzed 3066 participants 3163 participants
-0.31  (0.023) -0.83  (0.022)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide - Placebo) is equal to zero
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.63
Confidence Interval (2-Sided) 95%
-0.69 to -0.58
Estimation Comments Based on MMRM model: Change=Baseline HbA1c+Treatment+Visit+Treatment-by-Visit Interaction+Baseline HbA1c-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 8
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide - Placebo) is equal to zero
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-0.58 to -0.45
Estimation Comments Based on MMRM model: Change=Baseline HbA1c+Treatment+Visit+Treatment-by-Visit Interaction+Baseline HbA1c-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 16
12.Secondary Outcome
Title Change From Baseline in Body Weight
Hide Description Change from Baseline in body weight was analyzed using mixed model repeated measures including observed case data (does not impute any missing data). Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.
Time Frame Baseline and Months 8 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with value at Baseline and at the specified visit is presented (represented by n=X in category titles)
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4732 4731
Least Squares Mean (Standard Error)
Unit of Measure: Kilograms
Month 8, n=4217, 4286 Number Analyzed 4217 participants 4286 participants
-0.36  (0.062) -1.02  (0.061)
Month 16, n=3068, 3173 Number Analyzed 3068 participants 3173 participants
-0.53  (0.084) -1.36  (0.083)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide-Placebo) is equal to zero
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.66
Confidence Interval (2-Sided) 95%
-0.83 to -0.49
Estimation Comments Based on MMRM model: Change=Baseline Body Weight+Treatment+Visit+Treatment-by-Visit Interaction+Baseline Body Weight-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 8
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide - Placebo) is equal to zero
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.83
Confidence Interval (2-Sided) 95%
-1.06 to -0.60
Estimation Comments Based on MMRM model: Change=Baseline Body Weight+Treatment+Visit+Treatment-by-Visit Interaction+Baseline Body weight-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 16
13.Secondary Outcome
Title Change From Baseline in Treatment Related Impact Measures-Diabetes (TRIM-D) Total Score
Hide Description The TRIM-D is a 28 item treatment satisfaction measure with 5 domains assessing Treatment Burden, Daily Life, Diabetes Management, Compliance and Psychological Health. The raw score ranges for each subscale were: treatment burden (6 to 30), daily life (5 to 25), diabetes management (5 to 25), compliance (4 to 20) and psychological health (8 to 40), higher scores indicating better health state. Total raw score was determined by summing the raw scores for each of the subscales and the total score (transformed) was determined as [(raw score minus lowest possible raw score)/possible raw score range] x100. The possible total (transformed) score range is 0−100, where higher scores indicated better health state. Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.
Time Frame Baseline and Months 8 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with value at Baseline and at the specified visit is presented (represented by n=X in category titles)
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4732 4731
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Month 8, n=3013, 3041 Number Analyzed 3013 participants 3041 participants
4.53  (0.194) 6.92  (0.193)
Month 16, n=1738, 1840 Number Analyzed 1738 participants 1840 participants
4.80  (0.247) 7.13  (0.241)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide - Placebo) is equal to zero.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.39
Confidence Interval (2-Sided) 95%
1.85 to 2.93
Estimation Comments Based on MMRM model: Change=Baseline Total Score+Treatment+Visit+Treatment-by-Visit Interaction+Baseline Total Score-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 8
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide-Placebo) is equal to zero
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.33
Confidence Interval (2-Sided) 95%
1.66 to 3.01
Estimation Comments Based on MMRM model: Change=Baseline Total Score+Treatment+Visit+Treatment-by-Visit Interaction+Baseline Total Score-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 16
14.Secondary Outcome
Title Change From Baseline in EuroQol- 5 Dimension (EQ-5D) Visual Analogue Scale (VAS) Score
Hide Description The EQ-5D is a standardized instrument used to evaluate generic health-related quality of life, comprising 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. It provides a simple descriptive profile and a single index value for health status. The EQ-5D self-reported questionnaire includes a visual analog scale (VAS), which records the respondent's self-rated health status on a graduated (0–100) scale, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.
Time Frame Baseline and Months 8 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with value at Baseline and at the specified visit is presented (represented by n=X in category titles)
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4732 4731
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Month 8, n=3982, 4014 Number Analyzed 3982 participants 4014 participants
1.36  (0.217) 2.83  (0.216)
Month 16, n=2347, 2481 Number Analyzed 2347 participants 2481 participants
1.87  (0.287) 2.39  (0.279)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide-Placebo) is equal to zero.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.47
Confidence Interval (2-Sided) 95%
0.87 to 2.07
Estimation Comments Based on MMRM model: Change=Baseline Score+Treatment+Visit+Treatment-by-Visit Interaction+Baseline Score-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 8.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.192
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide - Placebo) is equal to zero
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
-0.26 to 1.31
Estimation Comments Based on MMRM model: Change=Baseline Score+Treatment+Visit+Treatment-by-Visit Interaction+Baseline Score-by-Visit Interaction. Difference of least squares means (Albiglutide - Placebo) is from MMRM model for Month 16
15.Secondary Outcome
Title Time to Death
Hide Description Time to death was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants who died/endpoint person-years) is presented along with 95% confidence interval. Endpoint person-years=(cumulative total time to event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the Vital Status follow-up time period.
Time Frame Median of 1.73 years for the Vital Status follow-up time period
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4732 4731
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Events per 100 person years
2.56
(2.22 to 2.93)
2.44
(2.11 to 2.81)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.644
Comments Two-sided p-value based on Wald test of HR=1 versus HR not equal to 1.
Method Wald test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.79 to 1.16
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
16.Secondary Outcome
Title Number of Participants With Non-fatal Serious Adverse Events (SAEs)
Hide Description SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before; is associated with liver injury and impaired liver function. Number of participants with on-therapy non-fatal SAEs are presented. Safety Population comprised of all randomized participants who received at least one dose of study treatment.
Time Frame Up to 2.7 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4715 4717
Measure Type: Count of Participants
Unit of Measure: Participants
974
  20.7%
891
  18.9%
17.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) Leading to Discontinuation of Investigational Product (AELD)
Hide Description The number of participants with on-therapy AEs leading to discontinuation of investigational product is reported.
Time Frame Up to 2.7 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4715 4717
Measure Type: Count of Participants
Unit of Measure: Participants
334
   7.1%
427
   9.1%
18.Secondary Outcome
Title Number of Participants With AEs of Special Interest
Hide Description The protocol defined AEs of special interest included: development of thyroid cancer; hematologic malignancy; pancreatic cancer; pancreatitis (investigator reported and pancreatitis positively adjudicated by the Pancreatic Adjudication Committee [PAC]); investigational product injection site reactions; immunological reactions; severe hypoglycemic events; hepatic events; hepatic enzyme elevations (including gamma glutamyl transferase [GGT]); serious gastrointestinal (GI) events; appendicitis; atrial fibrillation/flutter; pneumonia; worsening renal function and diabetic retinopathy. The number of participants with on-therapy AEs of special interest is reported.
Time Frame Up to 2.7 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4715 4717
Measure Type: Count of Participants
Unit of Measure: Participants
Thyroid cancer diagnosis
0
   0.0%
0
   0.0%
Hematologic malignancy
5
   0.1%
9
   0.2%
Pancreatic cancer
5
   0.1%
6
   0.1%
Investigational product injection site reaction
29
   0.6%
86
   1.8%
Hypersensitivity
48
   1.0%
45
   1.0%
Severe hypoglycemic events
55
   1.2%
31
   0.7%
Hepatic events
74
   1.6%
98
   2.1%
Hepatic enzyme elevations (including GGT)
34
   0.7%
51
   1.1%
Serious GI Events
87
   1.8%
92
   2.0%
Appendicitis
8
   0.2%
3
   0.1%
Atrial fibrillation/atrial flutter
131
   2.8%
108
   2.3%
Pneumonia
138
   2.9%
131
   2.8%
Renal impairment
319
   6.8%
279
   5.9%
Diabetic retinopathy
89
   1.9%
78
   1.7%
Investigator-reported pancreatitis
13
   0.3%
14
   0.3%
Pancreatitis positively adjudicated by PAC
7
   0.1%
10
   0.2%
19.Secondary Outcome
Title Change in Estimated Glomerular Filtration Rate (eGFR) Calculated Using Modification of Diet in Renal Disease (MDRD) Formula
Hide Description Blood samples were collected for the measurement of serum creatinine. Serum creatinine values were used to calculate eGFR using the MDRD formula, eGFR=175 x (serum creatinine)^-1.154 x (Age)^-0.203 x (0.742 if female) x (1.212 if African American). Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value. Change from Baseline in eGFR using Baseline data from Local or Central Laboratory, and post-Baseline Central Laboratory data for the on-treatment time period is presented.
Time Frame Baseline and Months 8 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with a value at Baseline and specified visit were analyzed (represented by n=X in category titles)
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4715 4717
Least Squares Mean (Standard Error)
Unit of Measure: Milliliter/minute/1.73 meter square
Month 8; n=3977,4008 Number Analyzed 3977 participants 4008 participants
1.22  (0.264) 0.10  (0.262)
Month 16; n=2354,2496 Number Analyzed 2354 participants 2496 participants
-0.90  (0.303) -1.33  (0.296)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide-Placebo) is equal to zero.
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.11
Confidence Interval (2-Sided) 95%
-1.84 to -0.39
Estimation Comments Based on MMRM model: Change=Baseline eGFR+Treatment+Visit+Treatment-by-Visit Interaction+Baseline eGFR-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 8.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.315
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide-Placebo) is equal to zero
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.43
Confidence Interval (2-Sided) 95%
-1.26 to 0.41
Estimation Comments Based on MMRM model: Change=Baseline eGFR+Treatment+Visit+Treatment-by-Visit Interaction+Baseline eGFR-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 16.
20.Secondary Outcome
Title Change From Baseline in Blood Pressure
Hide Description Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were taken with the participant in a semi-recumbent or seated position after at least a 5-minute rest period. Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.
Time Frame Baseline and Months 8,16,24 and end of study (up to 2.7 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with a value at Baseline and specified visit were analyzed (represented n=X in category titles)
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4715 4717
Mean (Standard Deviation)
Unit of Measure: Millimeter of mercury
SBP, Month 8; n=4241, 4319 Number Analyzed 4241 participants 4319 participants
-0.5  (17.33) -1.0  (16.80)
SBP, Month 16; n=3082, 3187 Number Analyzed 3082 participants 3187 participants
-0.5  (17.45) -0.9  (17.58)
SBP, Month 24; n=1133, 1198 Number Analyzed 1133 participants 1198 participants
-0.9  (18.62) -1.2  (17.51)
SBP, End of study; n=3897, 4015 Number Analyzed 3897 participants 4015 participants
0.0  (17.68) -0.4  (17.58)
DBP, Month 8; n=4241, 4319 Number Analyzed 4241 participants 4319 participants
-0.5  (10.26) -0.4  (10.12)
DBP, Month 16; n=3082, 3187 Number Analyzed 3082 participants 3187 participants
-0.9  (10.74) -0.5  (10.39)
DBP, Month 24; n=1133, 1198 Number Analyzed 1133 participants 1198 participants
-1.1  (10.87) -1.0  (10.29)
DBP, End of study; n=3897, 4015 Number Analyzed 3897 participants 4015 participants
-0.7  (10.66) -0.6  (10.57)
21.Secondary Outcome
Title Change From Baseline in Heart Rate
Hide Description Heart rate was measured with the participant in a semi-recumbent or seated position after at least a 5-minute rest period. Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.
Time Frame Baseline and Months 8, 16, 24 and end of study (up to 2.7 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants with a value at Baseline and specified visit were analyzed (represented n=X in category titles)
Arm/Group Title Placebo Albiglutide
Hide Arm/Group Description:
Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Overall Number of Participants Analyzed 4715 4717
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Month 8; n=4239, 4312 Number Analyzed 4239 participants 4312 participants
0.2  (9.99) 1.6  (10.07)
Month 16; n=3078, 3181 Number Analyzed 3078 participants 3181 participants
0.3  (10.19) 1.6  (10.16)
Month 24; n=1131, 1195 Number Analyzed 1131 participants 1195 participants
0.6  (10.84) 1.7  (10.32)
End of study; n=3892, 4005 Number Analyzed 3892 participants 4005 participants
0.8  (10.64) 1.8  (10.50)
Time Frame On-therapy non-SAEs and SAEs were reported on or after treatment start date and within 56 days after treatment stop date (Up to 2.7 years)
Adverse Event Reporting Description SAEs, non-SAELDs and non-SAEs of pre-specified interest were reported systematically in the Safety Population. Some investigators collected other non-SAEs for some participants (i.e. non-systematically). CV events referred for adjudication as study endpoints were not duplicate reported as AEs. Deaths were reported for ITT Population.
 
Arm/Group Title Albiglutide Placebo
Hide Arm/Group Description Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.. Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
All-Cause Mortality
Albiglutide Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   196/4731 (4.14%)      205/4732 (4.33%)    
Show Serious Adverse Events Hide Serious Adverse Events
Albiglutide Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   932/4717 (19.76%)      1022/4715 (21.68%)    
Blood and lymphatic system disorders     
Anaemia * 1  7/4717 (0.15%)  8 10/4715 (0.21%)  10
Iron deficiency anaemia * 1  5/4717 (0.11%)  5 3/4715 (0.06%)  3
Haemorrhagic anaemia * 1  5/4717 (0.11%)  5 1/4715 (0.02%)  1
Lymphadenopathy mediastinal * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Microcytic anaemia * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Anaemia of chronic disease * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Coagulopathy * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Haemolysis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Lymph node fibrosis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Normochromic anaemia * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Normocytic anaemia * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Pancytopenia * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Thrombocytopenia * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Cardiac disorders     
Atrial fibrillation * 1  45/4717 (0.95%)  48 41/4715 (0.87%)  47
Angina pectoris * 1  37/4717 (0.78%)  38 36/4715 (0.76%)  39
Coronary artery disease * 1  24/4717 (0.51%)  24 31/4715 (0.66%)  31
Atrial flutter * 1  6/4717 (0.13%)  6 14/4715 (0.30%)  15
Atrioventricular block complete * 1  11/4717 (0.23%)  11 5/4715 (0.11%)  5
Ventricular tachycardia * 1  6/4717 (0.13%)  7 9/4715 (0.19%)  10
Cardiac failure * 1  10/4717 (0.21%)  10 4/4715 (0.08%)  4
Cardiogenic shock * 1  9/4717 (0.19%)  9 4/4715 (0.08%)  4
Myocardial ischaemia * 1  6/4717 (0.13%)  6 7/4715 (0.15%)  7
Bradycardia * 1  8/4717 (0.17%)  8 4/4715 (0.08%)  4
Cardiac failure congestive * 1  3/4717 (0.06%)  3 9/4715 (0.19%)  10
Cardio-respiratory arrest * 1  5/4717 (0.11%)  5 5/4715 (0.11%)  6
Arteriosclerosis coronary artery * 1  4/4717 (0.08%)  4 5/4715 (0.11%)  5
Cardiac arrest * 1  4/4717 (0.08%)  4 5/4715 (0.11%)  5
Coronary artery stenosis * 1  3/4717 (0.06%)  3 6/4715 (0.13%)  6
Sinus node dysfunction * 1  2/4717 (0.04%)  2 6/4715 (0.13%)  6
Atrioventricular block second degree * 1  3/4717 (0.06%)  3 4/4715 (0.08%)  4
Ventricular fibrillation * 1  4/4717 (0.08%)  4 3/4715 (0.06%)  3
Aortic valve stenosis * 1  3/4717 (0.06%)  3 3/4715 (0.06%)  3
Acute coronary syndrome * 1  4/4717 (0.08%)  4 1/4715 (0.02%)  1
Pericarditis * 1  1/4717 (0.02%)  1 4/4715 (0.08%)  5
Supraventricular tachycardia * 1  3/4717 (0.06%)  3 2/4715 (0.04%)  2
Angina unstable * 1  2/4717 (0.04%)  2 2/4715 (0.04%)  2
Atrioventricular block * 1  1/4717 (0.02%)  1 3/4715 (0.06%)  3
Ventricular arrhythmia * 1  1/4717 (0.02%)  1 3/4715 (0.06%)  3
Arrhythmia * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  2
Bundle branch block left * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  2
Cardiopulmonary failure * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  2
Ischaemic cardiomyopathy * 1  0/4717 (0.00%)  0 3/4715 (0.06%)  3
Aortic valve disease * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Aortic valve incompetence * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Arrhythmia supraventricular * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Cardiac asthma * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Cardiac failure chronic * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Cardiomegaly * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Cardiomyopathy * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Cardiovascular disorder * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Coronary artery occlusion * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Left ventricular failure * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Myocardial fibrosis * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Sinus tachycardia * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Acute left ventricular failure * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Acute myocardial infarction * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Atrial thrombosis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Brugada syndrome * 1  1/4717 (0.02%)  2 0/4715 (0.00%)  0
Cardiorenal syndrome * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Coronary artery dissection * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Coronary no-reflow phenomenon * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Coronary ostial stenosis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Hypertensive heart disease * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Intracardiac thrombus * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Mitral valve incompetence * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Myocarditis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Palpitations * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Pericardial effusion * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Right ventricular failure * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Sinoatrial block * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Sinus arrest * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Sinus bradycardia * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Tachycardia * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Torsade de pointes * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Ventricular extrasystoles * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Congenital, familial and genetic disorders     
Adenomatous polyposis coli * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Haemorrhagic arteriovenous malformation * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Hypertrophic cardiomyopathy * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Phimosis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Ear and labyrinth disorders     
Vertigo * 1  2/4717 (0.04%)  2 5/4715 (0.11%)  6
Deafness * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Deafness unilateral * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Vertigo positional * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Endocrine disorders     
Adrenal mass * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Goitre * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Hyperparathyroidism * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Eye disorders     
Cataract * 1  7/4717 (0.15%)  7 5/4715 (0.11%)  6
Glaucoma * 1  1/4717 (0.02%)  1 6/4715 (0.13%)  6
Vitreous haemorrhage * 1  5/4717 (0.11%)  5 2/4715 (0.04%)  2
Diabetic retinopathy * 1  1/4717 (0.02%)  1 3/4715 (0.06%)  3
Eyelid ptosis * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Macular degeneration * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Blindness * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Choroidal detachment * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Diplopia * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Eye pain * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Hypotony of eye * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Posterior capsule rupture * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Retinal artery occlusion * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Retinal detachment * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Retinopathy * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Retinopathy proliferative * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Gastrointestinal disorders     
Gastrointestinal haemorrhage * 1  8/4717 (0.17%)  12 10/4715 (0.21%)  10
Gastritis * 1  5/4717 (0.11%)  5 8/4715 (0.17%)  8
Small intestinal obstruction * 1  5/4717 (0.11%)  5 5/4715 (0.11%)  6
Pancreatitis acute * 1  6/4717 (0.13%)  7 3/4715 (0.06%)  3
Inguinal hernia * 1  6/4717 (0.13%)  6 2/4715 (0.04%)  2
Colitis * 1  3/4717 (0.06%)  3 4/4715 (0.08%)  4
Upper gastrointestinal haemorrhage * 1  4/4717 (0.08%)  4 3/4715 (0.06%)  4
Abdominal pain * 1  2/4717 (0.04%)  2 4/4715 (0.08%)  4
Abdominal pain upper * 1  3/4717 (0.06%)  3 3/4715 (0.06%)  4
Diarrhoea * 1  4/4717 (0.08%)  4 2/4715 (0.04%)  2
Vomiting * 1  5/4717 (0.11%)  5 1/4715 (0.02%)  1
Duodenal ulcer * 1  1/4717 (0.02%)  1 4/4715 (0.08%)  4
Gastric ulcer * 1  3/4717 (0.06%)  3 2/4715 (0.04%)  2
Large intestine polyp * 1  2/4717 (0.04%)  2 3/4715 (0.06%)  3
Abdominal hernia * 1  3/4717 (0.06%)  3 1/4715 (0.02%)  1
Constipation * 1  3/4717 (0.06%)  3 1/4715 (0.02%)  1
Dyspepsia * 1  2/4717 (0.04%)  2 2/4715 (0.04%)  2
Impaired gastric emptying * 1  1/4717 (0.02%)  1 3/4715 (0.06%)  3
Gastric ulcer haemorrhage * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  2
Gastritis erosive * 1  2/4717 (0.04%)  2 1/4715 (0.02%)  1
Gastrooesophageal reflux disease * 1  2/4717 (0.04%)  2 1/4715 (0.02%)  1
Lower gastrointestinal haemorrhage * 1  2/4717 (0.04%)  5 1/4715 (0.02%)  1
Oesophagitis * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  2
Pancreatitis * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  2
Chronic gastritis * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Diverticulum intestinal * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Duodenal ulcer haemorrhage * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Enteritis * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Haemorrhoidal haemorrhage * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Hiatus hernia * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Intestinal obstruction * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Melaena * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Nausea * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Oesophageal varices haemorrhage * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Pancreatitis chronic * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Peptic ulcer * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Rectal haemorrhage * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Strangulated umbilical hernia * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Abdominal discomfort * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Alcoholic pancreatitis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Anal fistula * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Aortoenteric fistula * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Ascites * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Biliary ascites * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Colitis ischaemic * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Colitis ulcerative * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Crohn's disease * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Diabetic gastroparesis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Duodenal ulcer perforation * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Duodenitis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Dysphagia * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Epiploic appendagitis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Erosive oesophagitis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Faecaloma * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Gastric antral vascular ectasia * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Gastric haemorrhage * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Gastroenteritis eosinophilic * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Gastrointestinal disorder * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Gastrointestinal necrosis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Haematemesis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Haemorrhoids * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Hypoaesthesia oral * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Ileus * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Intestinal perforation * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Intestinal polyp * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Irritable bowel syndrome * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Lip oedema * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Oesophageal stenosis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Oesophageal ulcer * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Palatal ulcer * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Pancreatic duct stenosis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Peptic ulcer perforation * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Proctalgia * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Rectal polyp * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Retroperitoneal haematoma * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Umbilical hernia * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Uvulitis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Varices oesophageal * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
General disorders     
Non-cardiac chest pain * 1  15/4717 (0.32%)  19 22/4715 (0.47%)  23
Death * 1  10/4717 (0.21%)  10 14/4715 (0.30%)  14
Chest pain * 1  8/4717 (0.17%)  8 10/4715 (0.21%)  10
Multiple organ dysfunction syndrome * 1  6/4717 (0.13%)  6 6/4715 (0.13%)  6
Asthenia * 1  4/4717 (0.08%)  4 4/4715 (0.08%)  4
Sudden death * 1  2/4717 (0.04%)  2 3/4715 (0.06%)  3
Vascular stent stenosis * 1  3/4717 (0.06%)  3 2/4715 (0.04%)  2
Impaired healing * 1  1/4717 (0.02%)  1 3/4715 (0.06%)  4
Catheter site haemorrhage * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Generalised oedema * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Pyrexia * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Sudden cardiac death * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Systemic inflammatory response syndrome * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Accidental death * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Cardiac complication associated with device * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Complication associated with device * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Condition aggravated * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Discomfort * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Drug withdrawal syndrome * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Fatigue * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Incarcerated hernia * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Inflammation * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Mass * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Necrobiosis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Necrosis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Pain * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Soft tissue inflammation * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Treatment noncompliance * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Vascular stent occlusion * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Vascular stent thrombosis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Hepatobiliary disorders     
Cholelithiasis * 1  12/4717 (0.25%)  12 7/4715 (0.15%)  7
Cholecystitis * 1  7/4717 (0.15%)  7 5/4715 (0.11%)  5
Cholecystitis acute * 1  7/4717 (0.15%)  7 4/4715 (0.08%)  4
Bile duct stone * 1  2/4717 (0.04%)  2 1/4715 (0.02%)  1
Hepatic cirrhosis * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  2
Hepatic failure * 1  0/4717 (0.00%)  0 3/4715 (0.06%)  3
Biliary colic * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Cholecystitis chronic * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Hepatitis acute * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Ischaemic hepatitis * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Acute hepatic failure * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Drug-induced liver injury * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Hepatic steatosis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Hepatotoxicity * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Jaundice cholestatic * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Liver disorder * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Liver injury * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Non-alcoholic steatohepatitis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Immune system disorders     
Anaphylactic reaction * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Contrast media reaction * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Drug hypersensitivity * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Hypersensitivity * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Infections and infestations     
Pneumonia * 1  74/4717 (1.57%)  79 77/4715 (1.63%)  81
Sepsis * 1  23/4717 (0.49%)  23 28/4715 (0.59%)  29
Urinary tract infection * 1  26/4717 (0.55%)  27 23/4715 (0.49%)  27
Cellulitis * 1  20/4717 (0.42%)  22 20/4715 (0.42%)  20
Bronchitis * 1  10/4717 (0.21%)  10 11/4715 (0.23%)  12
Erysipelas * 1  9/4717 (0.19%)  9 12/4715 (0.25%)  14
Osteomyelitis * 1  6/4717 (0.13%)  6 14/4715 (0.30%)  14
Gangrene * 1  6/4717 (0.13%)  6 13/4715 (0.28%)  14
Gastroenteritis * 1  8/4717 (0.17%)  8 8/4715 (0.17%)  8
Urosepsis * 1  6/4717 (0.13%)  6 8/4715 (0.17%)  8
Diabetic foot infection * 1  4/4717 (0.08%)  6 9/4715 (0.19%)  9
Septic shock * 1  4/4717 (0.08%)  4 7/4715 (0.15%)  7
Postoperative wound infection * 1  6/4717 (0.13%)  6 4/4715 (0.08%)  4
Respiratory tract infection * 1  5/4717 (0.11%)  5 5/4715 (0.11%)  5
Appendicitis * 1  2/4717 (0.04%)  2 7/4715 (0.15%)  7
Influenza * 1  3/4717 (0.06%)  3 5/4715 (0.11%)  5
Localised infection * 1  3/4717 (0.06%)  3 4/4715 (0.08%)  4
Endocarditis * 1  1/4717 (0.02%)  1 5/4715 (0.11%)  5
Infected skin ulcer * 1  5/4717 (0.11%)  5 1/4715 (0.02%)  1
Pyelonephritis * 1  2/4717 (0.04%)  2 4/4715 (0.08%)  4
Staphylococcal infection * 1  2/4717 (0.04%)  2 4/4715 (0.08%)  4
Subcutaneous abscess * 1  2/4717 (0.04%)  2 4/4715 (0.08%)  4
Upper respiratory tract infection * 1  2/4717 (0.04%)  2 4/4715 (0.08%)  4
Abscess limb * 1  2/4717 (0.04%)  2 3/4715 (0.06%)  3
Anal abscess * 1  0/4717 (0.00%)  0 5/4715 (0.11%)  5
Bacteraemia * 1  3/4717 (0.06%)  4 2/4715 (0.04%)  2
Cystitis * 1  3/4717 (0.06%)  3 2/4715 (0.04%)  2
Infective exacerbation of chronic obstructive airways disease * 1  2/4717 (0.04%)  2 3/4715 (0.06%)  3
Lower respiratory tract infection * 1  1/4717 (0.02%)  1 4/4715 (0.08%)  5
Escherichia urinary tract infection * 1  3/4717 (0.06%)  3 1/4715 (0.02%)  1
Gastroenteritis viral * 1  3/4717 (0.06%)  3 1/4715 (0.02%)  1
Osteomyelitis acute * 1  2/4717 (0.04%)  2 2/4715 (0.04%)  2
Wound infection * 1  1/4717 (0.02%)  1 3/4715 (0.06%)  3
Arthritis bacterial * 1  3/4717 (0.06%)  3 0/4715 (0.00%)  0
Diabetic gangrene * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  2
Diverticulitis * 1  1/4717 (0.02%)  2 2/4715 (0.04%)  3
Epididymitis * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  2
Groin abscess * 1  2/4717 (0.04%)  2 1/4715 (0.02%)  1
Staphylococcal sepsis * 1  0/4717 (0.00%)  0 3/4715 (0.06%)  3
Viral infection * 1  2/4717 (0.04%)  2 1/4715 (0.02%)  1
Abscess soft tissue * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Acute sinusitis * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Bronchitis bacterial * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Clostridium difficile infection * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Device related infection * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Graft infection * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Hepatitis C * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Infection * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Intervertebral discitis * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Liver abscess * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Perirectal abscess * 1  2/4717 (0.04%)  3 0/4715 (0.00%)  0
Pneumonia viral * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Post procedural sepsis * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Pulmonary sepsis * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Sinusitis * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Staphylococcal bacteraemia * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Wound sepsis * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Abdominal abscess * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Abdominal sepsis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Abdominal wall abscess * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Abscess neck * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Abscess oral * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Arthritis infective * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  2
Beta haemolytic streptococcal infection * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Brain abscess * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Campylobacter gastroenteritis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Candiduria * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Cellulitis gangrenous * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Cellulitis of male external genital organ * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Cholecystitis infective * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Chronic sinusitis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Citrobacter infection * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Citrobacter sepsis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Clostridial infection * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Clostridium difficile colitis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Cystitis klebsiella * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Dacryocystitis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Dengue fever * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Dengue haemorrhagic fever * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Emphysematous pyelonephritis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Empyema * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Enterobacter sepsis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Enterococcal bacteraemia * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Enterocolitis infectious * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Extradural abscess * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Gas gangrene * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Gastroenteritis salmonella * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
H1N1 influenza * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Haematoma infection * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Helicobacter gastritis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Helicobacter infection * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Hepatitis E * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Herpes zoster * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Herpes zoster infection neurological * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Infected bite * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Infectious pleural effusion * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Lower respiratory tract infection bacterial * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Medical device site infection * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Meningitis pneumococcal * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Meningitis viral * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Nasopharyngitis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Oesophageal candidiasis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Oral candidiasis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Osteomyelitis chronic * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Otitis externa * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Otitis media * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Parotitis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Pharyngeal abscess * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Pneumonia bacterial * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Pneumonia haemophilus * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Pneumonia influenzal * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Pneumonia moraxella * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Post procedural cellulitis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Post procedural infection * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Prostatic abscess * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Psoas abscess * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Pyelonephritis acute * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Pyonephrosis * 1  1/4717 (0.02%)  2 0/4715 (0.00%)  0
Renal abscess * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Respiratory syncytial virus infection * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Retroperitoneal abscess * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Septic embolus * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Soft tissue infection * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Sternitis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Streptococcal bacteraemia * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Streptococcal endocarditis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Streptococcal sepsis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Systemic candida * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Systemic infection * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Tongue abscess * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Tonsillitis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Tuberculosis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Viral diarrhoea * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Viral upper respiratory tract infection * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Vulval abscess * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Injury, poisoning and procedural complications     
Fall * 1  7/4717 (0.15%)  8 6/4715 (0.13%)  7
Hip fracture * 1  6/4717 (0.13%)  6 2/4715 (0.04%)  2
Road traffic accident * 1  3/4717 (0.06%)  3 4/4715 (0.08%)  4
Upper limb fracture * 1  4/4717 (0.08%)  4 3/4715 (0.06%)  3
Rib fracture * 1  2/4717 (0.04%)  2 4/4715 (0.08%)  4
Ankle fracture * 1  2/4717 (0.04%)  2 3/4715 (0.06%)  3
Contusion * 1  2/4717 (0.04%)  2 3/4715 (0.06%)  4
Humerus fracture * 1  3/4717 (0.06%)  3 2/4715 (0.04%)  2
Joint dislocation * 1  2/4717 (0.04%)  2 3/4715 (0.06%)  3
Tibia fracture * 1  3/4717 (0.06%)  3 2/4715 (0.04%)  2
Craniocerebral injury * 1  4/4717 (0.08%)  4 0/4715 (0.00%)  0
Femur fracture * 1  1/4717 (0.02%)  1 3/4715 (0.06%)  3
Meniscus injury * 1  2/4717 (0.04%)  2 2/4715 (0.04%)  2
Peripheral artery restenosis * 1  0/4717 (0.00%)  0 4/4715 (0.08%)  4
Tendon rupture * 1  2/4717 (0.04%)  2 2/4715 (0.04%)  2
Coronary artery restenosis * 1  0/4717 (0.00%)  0 3/4715 (0.06%)  4
Fibula fracture * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  2
Incisional hernia * 1  3/4717 (0.06%)  3 0/4715 (0.00%)  0
Limb injury * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  2
Post procedural haematoma * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  2
Post procedural haemorrhage * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  3
Spinal fracture * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  2
Wound dehiscence * 1  0/4717 (0.00%)  0 3/4715 (0.06%)  3
Cardiac procedure complication * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Concussion * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Femoral neck fracture * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Hand fracture * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Head injury * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Lower limb fracture * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Lumbar vertebral fracture * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Postoperative thoracic procedure complication * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Postoperative wound complication * 1  1/4717 (0.02%)  2 1/4715 (0.02%)  1
Spinal compression fracture * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Subdural haematoma * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Vascular pseudoaneurysm * 1  2/4717 (0.04%)  2 0/4715 (0.00%)  0
Accidental overdose * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Adjacent segment degeneration * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Anastomotic stenosis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Animal bite * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Arterial restenosis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Carbon monoxide poisoning * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Cartilage injury * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Chest injury * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Fractured coccyx * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Fractured sacrum * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Gastrointestinal disorder postoperative * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Graft thrombosis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Gun shot wound * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Intentional overdose * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Joint injury * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Kidney contusion * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Ligament injury * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Ligament sprain * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Limb traumatic amputation * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Lip injury * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Multiple injuries * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Muscle rupture * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Open globe injury * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Overdose * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Patella fracture * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Perirenal haematoma * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Post procedural haematuria * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Post-traumatic pain * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Postoperative delirium * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Procedural pneumothorax * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Radius fracture * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Shunt stenosis * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Sternal fracture * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Subarachnoid haemorrhage * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Suture related complication * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Suture rupture * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Thoracic vertebral fracture * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Traumatic haematoma * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Traumatic intracranial haemorrhage * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Ulnar nerve injury * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Vascular graft occlusion * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Vascular graft thrombosis * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Wound evisceration * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Investigations     
Electrocardiogram QT prolonged * 1  4/4717 (0.08%)  4 0/4715 (0.00%)  0
Blood creatinine increased * 1  1/4717 (0.02%)  1 2/4715 (0.04%)  2
Hepatic enzyme increased * 1  3/4717 (0.06%)  3 0/4715 (0.00%)  0
Liver function test increased * 1  2/4717 (0.04%)  2 1/4715 (0.02%)  1
Glomerular filtration rate decreased * 1  0/4717 (0.00%)  0 2/4715 (0.04%)  2
Troponin increased * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Alanine aminotransferase increased * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Anticoagulation drug level above therapeutic * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Aspiration bronchial * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Blood alkaline phosphatase increased * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Blood glucose abnormal * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Blood ketone body increased * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Gamma-glutamyltransferase increased * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Myocardial necrosis marker increased * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Thyroid function test normal * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Weight decreased * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Weight increased * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Metabolism and nutrition disorders     
Hyperglycaemia * 1  16/4717 (0.34%)  16 30/4715 (0.64%)  42
Hypoglycaemia * 1  12/4717 (0.25%)  12 30/4715 (0.64%)  34
Diabetes mellitus inadequate control * 1  4/4717 (0.08%)  4 13/4715 (0.28%)  13
Dehydration * 1  3/4717 (0.06%)  3 9/4715 (0.19%)  9
Diabetic ketoacidosis * 1  5/4717 (0.11%)  5 6/4715 (0.13%)  6
Diabetic metabolic decompensation * 1  2/4717 (0.04%)  2 8/4715 (0.17%)  9
Hyperkalaemia * 1  5/4717 (0.11%)  5 5/4715 (0.11%)  5
Type 2 diabetes mellitus * 1  4/4717 (0.08%)  4 6/4715 (0.13%)  6
Diabetes mellitus * 1  2/4717 (0.04%)  2 6/4715 (0.13%)  6
Hypokalaemia * 1  1/4717 (0.02%)  1 4/4715 (0.08%)  4
Metabolic acidosis * 1  1/4717 (0.02%)  1 4/4715 (0.08%)  4
Obesity * 1  2/4717 (0.04%)  2 3/4715 (0.06%)  3
Hyperglycaemic hyperosmolar nonketotic syndrome * 1  2/4717 (0.04%)  2 2/4715 (0.04%)  3
Lactic acidosis * 1  0/4717 (0.00%)  0 3/4715 (0.06%)  3
Hypocalcaemia * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Hypomagnesaemia * 1  1/4717 (0.02%)  1 1/4715 (0.02%)  1
Decreased appetite * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Failure to thrive * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Fluid overload * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Food intolerance * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Gout * 1  0/4717 (0.00%)  0 1/4715 (0.02%)  1
Hypercalcaemia * 1  1/4717 (0.02%)  1 0/4715 (0.00%)  0
Hyperosmolar state * 1