Trial Outcomes & Findings for Effect of Albiglutide, When Added to Standard Blood Glucose Lowering Therapies, on Major Cardiovascular Events in Subjects With Type 2 Diabetes Mellitus (NCT NCT02465515)

Last Updated: 2019-03-06

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

9463 participants

Primary outcome timeframe

Median of 1.65 person years for CV follow-up time period

Results posted on

2019-03-06

Participant Flow

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.

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

Participant milestones

Participant milestones
Measure	Placebo 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 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 Study STARTED	4732	4731
Overall Study COMPLETED	4578	4620
Overall Study NOT COMPLETED	154	111

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 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 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 Study Investigator site closed	4	5
Overall Study Withdrawal by Subject	74	43
Overall Study Physician Decision	8	12
Overall Study Lost to Follow-up	68	51

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=4732 Participants 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 n=4731 Participants 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 n=9463 Participants Total of all reporting groups
Sex: Female, Male Female	1467 Participants n=5 Participants	1427 Participants n=7 Participants	2894 Participants n=5 Participants
Sex: Female, Male Male	3265 Participants n=5 Participants	3304 Participants n=7 Participants	6569 Participants n=5 Participants
Race/Ethnicity, Customized Race, customized · American Indian (Amer. Ind.) or Alaska Native	238 Participants n=5 Participants	280 Participants n=7 Participants	518 Participants n=5 Participants
Race/Ethnicity, Customized Race, customized · Central/South Asian Heritage (Her.)	27 Participants n=5 Participants	25 Participants n=7 Participants	52 Participants n=5 Participants
Race/Ethnicity, Customized Race, customized · Japanese Her./East Asian Her/South East Asian Her.	215 Participants n=5 Participants	204 Participants n=7 Participants	419 Participants n=5 Participants
Race/Ethnicity, Customized Race, customized · Black or African American (Amer.)	118 Participants n=5 Participants	121 Participants n=7 Participants	239 Participants n=5 Participants
Race/Ethnicity, Customized Race, customized · Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Race, customized · White	4024 Participants n=5 Participants	4006 Participants n=7 Participants	8030 Participants n=5 Participants
Race/Ethnicity, Customized Race, customized · Amer Ind. or Alaska Native & Black or African Amer	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race, customized · Asian & Black or African Amer.	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race, customized · Asian & White	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race, customized · Black or African Amer. & White	81 Participants n=5 Participants	67 Participants n=7 Participants	148 Participants n=5 Participants
Race/Ethnicity, Customized Race, customized · Unknown	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race, customized · Amer. Ind. or Alaska Native & White	24 Participants n=5 Participants	20 Participants n=7 Participants	44 Participants n=5 Participants
Age, Continuous	64.2 Years STANDARD_DEVIATION 8.65 • n=5 Participants	64.1 Years STANDARD_DEVIATION 8.71 • n=7 Participants	64.1 Years STANDARD_DEVIATION 8.68 • n=5 Participants

PRIMARY outcome

Timeframe: Median of 1.65 person years for CV follow-up time period

Population: ITT Population

Outcome measures

Outcome measures
Measure	Albiglutide n=4731 Participants 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.	Placebo n=4732 Participants 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.
Time to First Occurrence of Major Adverse Cardiovascular Events (MACE) During Cardiovascular (CV) Follow-up Time Period	4.57 Events per 100 person years Interval 4.1 to 5.08	5.87 Events per 100 person years Interval 5.33 to 6.45

SECONDARY outcome

Timeframe: Median of 1.65 person years for CV follow-up time period

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4731 Participants 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.	Placebo n=4732 Participants 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.
Time to First Occurrence of MACE or Urgent Revascularization for Unstable Angina	5.06 Events per 100 person years Interval 4.56 to 5.6	6.45 Events per 100 person years Interval 5.88 to 7.06

SECONDARY outcome

Timeframe: Median of 1.65 person years for the CV follow-up time period

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4731 Participants 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.	Placebo n=4732 Participants 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.
Time to Adjudicated CV Death	1.61 Events per 100 person years Interval 1.33 to 1.92	1.72 Events per 100 person years Interval 1.44 to 2.04

SECONDARY outcome

Timeframe: Median of 1.65 person years for CV follow-up time period

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4731 Participants 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.	Placebo n=4732 Participants 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.
Time to First Occurrence of Adjudicated MI	2.43 Events per 100 person years Interval 2.09 to 2.81	3.26 Events per 100 person years Interval 2.86 to 3.7

SECONDARY outcome

Timeframe: Median of 1.65 person years for CV follow-up time period

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4731 Participants 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.	Placebo n=4732 Participants 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.
Time to First Occurrence of Adjudicated Stroke	1.25 Events per 100 person years Interval 1.01 to 1.53	1.45 Events per 100 person years Interval 1.19 to 1.74

SECONDARY outcome

Timeframe: Median of 1.65 person years for CV follow-up time period

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4731 Participants 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.	Placebo n=4732 Participants 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.
Time to First Occurrence of Adjudicated CV Death or Hospitalization for Heart Failure (HF)	2.49 Events per 100 person years Interval 2.15 to 2.88	2.92 Events per 100 person years Interval 2.55 to 3.34

SECONDARY outcome

Timeframe: Up to 2.7 years

Population: Non-Insulin Population

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=1871 Participants 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.	Placebo n=1995 Participants 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.
Time to Initiation of Insulin of More Than 3 Months Duration for Those Participants Not Treated With Insulin at Study Start	3.56 Events per 100 person years Interval 2.92 to 4.31	8.58 Events per 100 person years Interval 7.56 to 9.7

SECONDARY outcome

Timeframe: Up to 2.7 years

Population: Basal Insulin Population

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).

Outcome measures

Outcome measures
Measure	Albiglutide n=1028 Participants 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.	Placebo n=1040 Participants 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.
Time to Initiation of Prandial Insulin in Those Participants on Basal Insulin at Study Start	3.59 Events per 100 person years Interval 2.73 to 4.63	5.09 Events per 100 person years Interval 4.06 to 6.31

SECONDARY outcome

Timeframe: Months 8, 16, 24 and final assessment (up to 2.7 years)

Population: 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)

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4731 Participants 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.	Placebo n=4732 Participants 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.
Percentage of Participants Achieving Composite Metabolic Endpoint Month 8, n=4127, 4195	32.2 Percentage of participants	15.4 Percentage of participants
Percentage of Participants Achieving Composite Metabolic Endpoint Month 16, n=3026, 3118	28.7 Percentage of participants	16.5 Percentage of participants
Percentage of Participants Achieving Composite Metabolic Endpoint Month 24, n=1119, 1173	28.6 Percentage of participants	17.8 Percentage of participants
Percentage of Participants Achieving Composite Metabolic Endpoint Final assessment, n=4401, 4455	26.0 Percentage of participants	15.1 Percentage of participants

SECONDARY outcome

Timeframe: Up to 2.7 years

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4731 Participants 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.	Placebo n=4732 Participants 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.
Time to First Occurrence of a Clinically Important Microvascular Event	0.46 Events per 100 person years Interval 0.32 to 0.63	0.69 Events per 100 person years Interval 0.52 to 0.9

SECONDARY outcome

Timeframe: Baseline and Months 8 and 16

Population: ITT Population. Only those participants with value at Baseline and at the specified visit is presented (represented by n=X in category titles)

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4731 Participants 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.	Placebo n=4732 Participants 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.
Change From Baseline in HbA1c Month 8, n=4211, 4289	-0.92 Percentage of HbA1c Standard Error 0.019	-0.28 Percentage of HbA1c Standard Error 0.020
Change From Baseline in HbA1c Month 16, n=3066, 3163	-0.83 Percentage of HbA1c Standard Error 0.022	-0.31 Percentage of HbA1c Standard Error 0.023

SECONDARY outcome

Timeframe: Baseline and Months 8 and 16

Population: ITT Population. Only those participants with value at Baseline and at the specified visit is presented (represented by n=X in category titles)

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4731 Participants 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.	Placebo n=4732 Participants 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.
Change From Baseline in Body Weight Month 8, n=4217, 4286	-1.02 Kilograms Standard Error 0.061	-0.36 Kilograms Standard Error 0.062
Change From Baseline in Body Weight Month 16, n=3068, 3173	-1.36 Kilograms Standard Error 0.083	-0.53 Kilograms Standard Error 0.084

SECONDARY outcome

Timeframe: Baseline and Months 8 and 16

Population: ITT Population. Only those participants with value at Baseline and at the specified visit is presented (represented by n=X in category titles)

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4731 Participants 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.	Placebo n=4732 Participants 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.
Change From Baseline in Treatment Related Impact Measures-Diabetes (TRIM-D) Total Score Month 8, n=3013, 3041	6.92 Scores on a scale Standard Error 0.193	4.53 Scores on a scale Standard Error 0.194
Change From Baseline in Treatment Related Impact Measures-Diabetes (TRIM-D) Total Score Month 16, n=1738, 1840	7.13 Scores on a scale Standard Error 0.241	4.80 Scores on a scale Standard Error 0.247

SECONDARY outcome

Timeframe: Baseline and Months 8 and 16

Population: ITT Population. Only those participants with value at Baseline and at the specified visit is presented (represented by n=X in category titles)

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4731 Participants 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.	Placebo n=4732 Participants 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.
Change From Baseline in EuroQol- 5 Dimension (EQ-5D) Visual Analogue Scale (VAS) Score Month 8, n=3982, 4014	2.83 Scores on a scale Standard Error 0.216	1.36 Scores on a scale Standard Error 0.217
Change From Baseline in EuroQol- 5 Dimension (EQ-5D) Visual Analogue Scale (VAS) Score Month 16, n=2347, 2481	2.39 Scores on a scale Standard Error 0.279	1.87 Scores on a scale Standard Error 0.287

SECONDARY outcome

Timeframe: Median of 1.73 years for the Vital Status follow-up time period

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4731 Participants 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.	Placebo n=4732 Participants 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.
Time to Death	2.44 Events per 100 person years Interval 2.11 to 2.81	2.56 Events per 100 person years Interval 2.22 to 2.93

SECONDARY outcome

Timeframe: Up to 2.7 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4717 Participants 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.	Placebo n=4715 Participants 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.
Number of Participants With Non-fatal Serious Adverse Events (SAEs)	891 Participants	974 Participants

SECONDARY outcome

Timeframe: Up to 2.7 years

Population: Safety Population

The number of participants with on-therapy AEs leading to discontinuation of investigational product is reported.

Outcome measures

Outcome measures
Measure	Albiglutide n=4717 Participants 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.	Placebo n=4715 Participants 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.
Number of Participants With Adverse Events (AEs) Leading to Discontinuation of Investigational Product (AELD)	427 Participants	334 Participants

SECONDARY outcome

Timeframe: Up to 2.7 years

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4717 Participants 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.	Placebo n=4715 Participants 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.
Number of Participants With AEs of Special Interest Atrial fibrillation/atrial flutter	108 Participants	131 Participants
Number of Participants With AEs of Special Interest Pneumonia	131 Participants	138 Participants
Number of Participants With AEs of Special Interest Renal impairment	279 Participants	319 Participants
Number of Participants With AEs of Special Interest Diabetic retinopathy	78 Participants	89 Participants
Number of Participants With AEs of Special Interest Investigator-reported pancreatitis	14 Participants	13 Participants
Number of Participants With AEs of Special Interest Pancreatitis positively adjudicated by PAC	10 Participants	7 Participants
Number of Participants With AEs of Special Interest Thyroid cancer diagnosis	0 Participants	0 Participants
Number of Participants With AEs of Special Interest Hematologic malignancy	9 Participants	5 Participants
Number of Participants With AEs of Special Interest Pancreatic cancer	6 Participants	5 Participants
Number of Participants With AEs of Special Interest Investigational product injection site reaction	86 Participants	29 Participants
Number of Participants With AEs of Special Interest Hypersensitivity	45 Participants	48 Participants
Number of Participants With AEs of Special Interest Severe hypoglycemic events	31 Participants	55 Participants
Number of Participants With AEs of Special Interest Hepatic events	98 Participants	74 Participants
Number of Participants With AEs of Special Interest Hepatic enzyme elevations (including GGT)	51 Participants	34 Participants
Number of Participants With AEs of Special Interest Serious GI Events	92 Participants	87 Participants
Number of Participants With AEs of Special Interest Appendicitis	3 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline and Months 8 and 16

Population: Safety Population. Only those participants with a value at Baseline and specified visit were analyzed (represented by n=X in category titles)

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4717 Participants 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.	Placebo n=4715 Participants 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.
Change in Estimated Glomerular Filtration Rate (eGFR) Calculated Using Modification of Diet in Renal Disease (MDRD) Formula Month 8; n=3977,4008	0.10 Milliliter/minute/1.73 meter square Standard Error 0.262	1.22 Milliliter/minute/1.73 meter square Standard Error 0.264
Change in Estimated Glomerular Filtration Rate (eGFR) Calculated Using Modification of Diet in Renal Disease (MDRD) Formula Month 16; n=2354,2496	-1.33 Milliliter/minute/1.73 meter square Standard Error 0.296	-0.90 Milliliter/minute/1.73 meter square Standard Error 0.303

SECONDARY outcome

Timeframe: Baseline and Months 8,16,24 and end of study (up to 2.7 years)

Population: Safety Population. Only those participants with a value at Baseline and specified visit were analyzed (represented n=X in category titles)

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4717 Participants 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.	Placebo n=4715 Participants 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.
Change From Baseline in Blood Pressure SBP, Month 8; n=4241, 4319	-1.0 Millimeter of mercury Standard Deviation 16.80	-0.5 Millimeter of mercury Standard Deviation 17.33
Change From Baseline in Blood Pressure SBP, Month 16; n=3082, 3187	-0.9 Millimeter of mercury Standard Deviation 17.58	-0.5 Millimeter of mercury Standard Deviation 17.45
Change From Baseline in Blood Pressure SBP, Month 24; n=1133, 1198	-1.2 Millimeter of mercury Standard Deviation 17.51	-0.9 Millimeter of mercury Standard Deviation 18.62
Change From Baseline in Blood Pressure SBP, End of study; n=3897, 4015	-0.4 Millimeter of mercury Standard Deviation 17.58	0.0 Millimeter of mercury Standard Deviation 17.68
Change From Baseline in Blood Pressure DBP, Month 8; n=4241, 4319	-0.4 Millimeter of mercury Standard Deviation 10.12	-0.5 Millimeter of mercury Standard Deviation 10.26
Change From Baseline in Blood Pressure DBP, Month 16; n=3082, 3187	-0.5 Millimeter of mercury Standard Deviation 10.39	-0.9 Millimeter of mercury Standard Deviation 10.74
Change From Baseline in Blood Pressure DBP, Month 24; n=1133, 1198	-1.0 Millimeter of mercury Standard Deviation 10.29	-1.1 Millimeter of mercury Standard Deviation 10.87
Change From Baseline in Blood Pressure DBP, End of study; n=3897, 4015	-0.6 Millimeter of mercury Standard Deviation 10.57	-0.7 Millimeter of mercury Standard Deviation 10.66

SECONDARY outcome

Timeframe: Baseline and Months 8, 16, 24 and end of study (up to 2.7 years)

Population: Safety Population. Only those participants with a value at Baseline and specified visit were analyzed (represented n=X in category titles)

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.

Outcome measures

Outcome measures
Measure	Albiglutide n=4717 Participants 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.	Placebo n=4715 Participants 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.
Change From Baseline in Heart Rate End of study; n=3892, 4005	1.8 Beats per minute Standard Deviation 10.50	0.8 Beats per minute Standard Deviation 10.64
Change From Baseline in Heart Rate Month 8; n=4239, 4312	1.6 Beats per minute Standard Deviation 10.07	0.2 Beats per minute Standard Deviation 9.99
Change From Baseline in Heart Rate Month 16; n=3078, 3181	1.6 Beats per minute Standard Deviation 10.16	0.3 Beats per minute Standard Deviation 10.19
Change From Baseline in Heart Rate Month 24; n=1131, 1195	1.7 Beats per minute Standard Deviation 10.32	0.6 Beats per minute Standard Deviation 10.84

Adverse Events

Albiglutide

Serious events: 932 serious events

Other events: 0 other events

Deaths: 196 deaths

Placebo

Serious events: 1022 serious events

Other events: 0 other events

Deaths: 205 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER