Trial Outcomes & Findings for A Comparative Effectiveness Study of Major Glycemia-lowering Medications for Treatment of Type 2 Diabetes (NCT NCT01794143)

Last Updated: 2026-02-10

Results Overview

The primary metabolic outcome is the time to primary failure defined as an HbA1c\>=7% (53mmol/mol), subsequently confirmed, after addition of randomly assigned glucose-lowering medication at baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

7850 participants

Primary outcome timeframe

Quarterly for 4 to 7 years

Results posted on

2026-02-10

Participant Flow

During a run-in period of 6 to 14 weeks before randomization, the metformin dose was increased to a minimum of 1000 mg per day, with a target maximal dose (one that could be taken without unacceptable side effects) of 2000 mg per day. Of the 7,850 participants consented for study run-in, 5,047 were randomized into the trial.

Participant milestones

Participant milestones
Measure	Glargine Insulin U-100 Glargine Insulin U-100 was administered daily at an initial dose of up to 20 U and adjusted according to glucose levels monitored by the participant and to avoid hypoglycemia.	Glimepiride Sulfonylurea glimepiride was increased from 1 to 2 mg to a maximum of 8 mg per day, administered in divided doses and adjusted according to glucose levels monitored by the participant and to avoid hypoglycemia.	Liraglutide GLP-1 analog liraglutide was initiated at a dose of 0.6 mg, with escalation to a maximum dose of 1.8 mg daily, depending on gastrointestinal side effects.	Sitagliptin DPP-4 inhibitor sitagliptin was initiated at a dose of 100 mg, with the dose adjusted according to kidney function.
Overall Study STARTED	1263	1254	1262	1268
Overall Study COMPLETED	1138	1142	1156	1144
Overall Study NOT COMPLETED	125	112	106	124

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Comparative Effectiveness Study of Major Glycemia-lowering Medications for Treatment of Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glargine Insulin U-100 n=1263 Participants Glargine Insulin U-100 was administered daily at an initial dose of up to 20 U and adjusted according to glucose levels monitored by the participant and to avoid hypoglycemia.	Glimepiride n=1254 Participants Sulfonylurea glimepiride was increased from 1 to 2 mg to a maximum of 8 mg per day, administered in divided doses and adjusted according to glucose levels monitored by the participant and to avoid hypoglycemia.	Liraglutide n=1262 Participants GLP-1 analog liraglutide was initiated at a dose of 0.6 mg, with escalation to a maximum dose of 1.8 mg daily, depending on gastrointestinal side effects.	Sitagliptin n=1268 Participants DPP-4 inhibitor sitagliptin was initiated at a dose of 100 mg, with the dose adjusted according to kidney function.	Total n=5047 Participants Total of all reporting groups
Age, Continuous	57.0 years STANDARD_DEVIATION 9.9 • n=41 Participants	57.1 years STANDARD_DEVIATION 10.1 • n=1581 Participants	57.4 years STANDARD_DEVIATION 9.9 • n=4626 Participants	57.2 years STANDARD_DEVIATION 10.1 • n=72 Participants	57.2 years STANDARD_DEVIATION 10.0
Sex: Female, Male Female	452 Participants n=41 Participants	476 Participants n=1581 Participants	439 Participants n=4626 Participants	470 Participants n=72 Participants	1837 Participants
Sex: Female, Male Male	811 Participants n=41 Participants	778 Participants n=1581 Participants	823 Participants n=4626 Participants	798 Participants n=72 Participants	3210 Participants
Race (NIH/OMB) American Indian or Alaska Native	33 Participants n=41 Participants	30 Participants n=1581 Participants	40 Participants n=4626 Participants	34 Participants n=72 Participants	137 Participants
Race (NIH/OMB) Asian	34 Participants n=41 Participants	47 Participants n=1581 Participants	47 Participants n=4626 Participants	54 Participants n=72 Participants	182 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	5 Participants n=41 Participants	7 Participants n=1581 Participants	8 Participants n=4626 Participants	8 Participants n=72 Participants	28 Participants
Race (NIH/OMB) Black or African American	253 Participants n=41 Participants	271 Participants n=1581 Participants	251 Participants n=4626 Participants	225 Participants n=72 Participants	1000 Participants
Race (NIH/OMB) White	837 Participants n=41 Participants	808 Participants n=1581 Participants	815 Participants n=4626 Participants	854 Participants n=72 Participants	3314 Participants
Race (NIH/OMB) More than one race	82 Participants n=41 Participants	71 Participants n=1581 Participants	82 Participants n=4626 Participants	84 Participants n=72 Participants	319 Participants
Race (NIH/OMB) Unknown or Not Reported	19 Participants n=41 Participants	20 Participants n=1581 Participants	19 Participants n=4626 Participants	9 Participants n=72 Participants	67 Participants
HbA1c	7.5 % STANDARD_DEVIATION 0.5 • n=41 Participants	7.5 % STANDARD_DEVIATION 0.5 • n=1581 Participants	7.5 % STANDARD_DEVIATION 0.5 • n=4626 Participants	7.5 % STANDARD_DEVIATION 0.5 • n=72 Participants	7.5 % STANDARD_DEVIATION 0.5

PRIMARY outcome

Timeframe: Quarterly for 4 to 7 years

Outcome measures

Outcome measures
Measure	Glargine Insulin U-100 n=1263 Participants Glargine Insulin U-100 was administered daily at an initial dose of up to 20 U and adjusted according to glucose levels monitored by the participant and to avoid hypoglycemia.	Glimepiride n=1254 Participants Sulfonylurea glimepiride was increased from 1 to 2 mg to a maximum of 8 mg per day, administered in divided doses and adjusted according to glucose levels monitored by the participant and to avoid hypoglycemia.	Liraglutide n=1262 Participants GLP-1 analog liraglutide was initiated at a dose of 0.6 mg, with escalation to a maximum dose of 1.8 mg daily, depending on gastrointestinal side effects.	Sitagliptin n=1268 Participants DPP-4 inhibitor
Time to HbA1c>=7%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication	1.3 years Interval 0.6 to 2.5	1.3 years Interval 0.6 to 2.3	1.5 years Interval 0.6 to 2.7	0.8 years Interval 0.5 to 2.0

PRIMARY outcome

Timeframe: Quarterly, 4-7 years

Number of participants who reached primary failure defined as an HbA1c\>=7% (53mmol/mol), subsequently confirmed, after addition of randomly assigned glucose-lowering medication at baseline.

Outcome measures

Outcome measures
Measure	Glargine Insulin U-100 n=1263 Participants Glargine Insulin U-100 was administered daily at an initial dose of up to 20 U and adjusted according to glucose levels monitored by the participant and to avoid hypoglycemia.	Glimepiride n=1254 Participants Sulfonylurea glimepiride was increased from 1 to 2 mg to a maximum of 8 mg per day, administered in divided doses and adjusted according to glucose levels monitored by the participant and to avoid hypoglycemia.	Liraglutide n=1262 Participants GLP-1 analog liraglutide was initiated at a dose of 0.6 mg, with escalation to a maximum dose of 1.8 mg daily, depending on gastrointestinal side effects.	Sitagliptin n=1268 Participants DPP-4 inhibitor
HbA1c>=7%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication	852 Participants	908 Participants	860 Participants	981 Participants

SECONDARY outcome

Timeframe: Quarterly, 4-6 years

The secondary metabolic outcome is time to HbA1c\>7.5% (58 mmol/mol), confirmed, after addition of randomly assigned glucose-lowering medication at baseline.

Outcome measures

Outcome measures
Measure	Glargine Insulin U-100 n=1263 Participants Glargine Insulin U-100 was administered daily at an initial dose of up to 20 U and adjusted according to glucose levels monitored by the participant and to avoid hypoglycemia.	Glimepiride n=1254 Participants Sulfonylurea glimepiride was increased from 1 to 2 mg to a maximum of 8 mg per day, administered in divided doses and adjusted according to glucose levels monitored by the participant and to avoid hypoglycemia.	Liraglutide n=1262 Participants GLP-1 analog liraglutide was initiated at a dose of 0.6 mg, with escalation to a maximum dose of 1.8 mg daily, depending on gastrointestinal side effects.	Sitagliptin n=1268 Participants DPP-4 inhibitor
Time to HbA1c>7.5%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication.	2.1 years Interval 1.0 to 3.5	2.0 years Interval 1.1 to 3.3	2.2 years Interval 1.0 to 3.5	1.7 years Interval 0.8 to 3.0

SECONDARY outcome

Timeframe: Quarterly for 4 to 7 years

Number of participants who reached primary failure defined as an HbA1c\>7.5% (58 mmol/mol), confirmed, after addition of randomly assigned glucose-lowering medication at baseline.

Outcome measures

Outcome measures
Measure	Glargine Insulin U-100 n=1263 Participants Glargine Insulin U-100 was administered daily at an initial dose of up to 20 U and adjusted according to glucose levels monitored by the participant and to avoid hypoglycemia.	Glimepiride n=1254 Participants Sulfonylurea glimepiride was increased from 1 to 2 mg to a maximum of 8 mg per day, administered in divided doses and adjusted according to glucose levels monitored by the participant and to avoid hypoglycemia.	Liraglutide n=1262 Participants GLP-1 analog liraglutide was initiated at a dose of 0.6 mg, with escalation to a maximum dose of 1.8 mg daily, depending on gastrointestinal side effects.	Sitagliptin n=1268 Participants DPP-4 inhibitor
HbA1c>7.5%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication.	498 Participants	633 Participants	583 Participants	697 Participants

Adverse Events

Glargine Insulin U-100

Serious events: 259 serious events

Other events: 0 other events

Deaths: 42 deaths

Glimepiride

Serious events: 315 serious events

Other events: 0 other events

Deaths: 43 deaths

Liraglutide

Serious events: 204 serious events

Other events: 0 other events

Deaths: 27 deaths

Sitagliptin

Serious events: 272 serious events

Other events: 0 other events

Deaths: 41 deaths

Study Run-In (Metformin Only)

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Glargine Insulin U-100 n=1263 participants at risk Glargine Insulin U-100 was administered daily at an initial dose of up to 20 U and adjusted according to glucose levels monitored by the participant and to avoid hypoglycemia.	Glimepiride n=1254 participants at risk Sulfonylurea glimepiride was increased from 1 to 2 mg to a maximum of 8 mg per day, administered in divided doses and adjusted according to glucose levels monitored by the participant and to avoid hypoglycemia.	Liraglutide n=1262 participants at risk GLP-1 analog liraglutide was initiated at a dose of 0.6 mg, with escalation to a maximum dose of 1.8 mg daily, depending on gastrointestinal side effects.	Sitagliptin n=1268 participants at risk DPP-4 inhibitor sitagliptin was initiated at a dose of 100 mg, with the dose adjusted according to kidney function.	Study Run-In (Metformin Only) n=7850 participants at risk During a run-in period of 6 to 14 weeks before randomization, the metformin dose was increased to a minimum of 1000 mg per day, with a target maximal dose (one that could be taken without unacceptable side effects) of 2000 mg per day.
Cardiac disorders Myocardial infarction	2.4% 30/1263 • Number of events 41 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	2.4% 30/1254 • Number of events 33 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	1.7% 21/1262 • Number of events 22 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	2.8% 35/1268 • Number of events 37 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Metabolism and nutrition disorders Severe Hypoglycemia	1.3% 17/1263 • Number of events 21 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	2.2% 28/1254 • Number of events 38 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.95% 12/1262 • Number of events 13 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.71% 9/1268 • Number of events 10 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Cardiac disorders Heart failure	2.1% 26/1263 • Number of events 35 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	2.4% 30/1254 • Number of events 49 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	1.1% 14/1262 • Number of events 18 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	2.4% 30/1268 • Number of events 56 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Cardiac disorders Unstable angina	0.71% 9/1263 • Number of events 10 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.96% 12/1254 • Number of events 14 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.55% 7/1262 • Number of events 7 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	1.2% 15/1268 • Number of events 17 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Gastrointestinal disorders Pancreatitis	0.79% 10/1263 • Number of events 12 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	1.3% 16/1254 • Number of events 18 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.87% 11/1262 • Number of events 13 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.47% 6/1268 • Number of events 6 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
General disorders Stent thrombosis	0.00% 0/1263 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1254 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.16% 2/1262 • Number of events 6 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.16% 2/1268 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Metabolism and nutrition disorders Lactic Acidosis	0.48% 6/1263 • Number of events 6 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.40% 5/1254 • Number of events 5 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.48% 6/1262 • Number of events 7 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.71% 9/1268 • Number of events 11 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.48% 6/1263 • Number of events 6 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.56% 7/1254 • Number of events 7 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.24% 3/1262 • Number of events 3 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.32% 4/1268 • Number of events 4 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Blood cancer other than leukemia	0.08% 1/1263 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.24% 3/1254 • Number of events 3 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.16% 2/1262 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/1268 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.40% 5/1263 • Number of events 5 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.40% 5/1254 • Number of events 5 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.32% 4/1262 • Number of events 4 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.39% 5/1268 • Number of events 5 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer, Unknown primary	0.24% 3/1263 • Number of events 3 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1254 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1262 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1268 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) CNS/brain cancer	0.00% 0/1263 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1254 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/1262 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1268 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.16% 2/1263 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.40% 5/1254 • Number of events 5 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.16% 2/1262 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.32% 4/1268 • Number of events 4 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Esophageal cancer	0.08% 1/1263 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.16% 2/1254 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1262 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1268 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gall Bladder cancer	0.00% 0/1263 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1254 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/1262 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/1268 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Head/neck cancer	0.24% 3/1263 • Number of events 3 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.32% 4/1254 • Number of events 4 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1262 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.24% 3/1268 • Number of events 3 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Kidney cancer	0.08% 1/1263 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.40% 5/1254 • Number of events 5 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.40% 5/1262 • Number of events 5 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.71% 9/1268 • Number of events 9 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukemia	0.16% 2/1263 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.16% 2/1254 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.16% 2/1262 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.16% 2/1268 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Liver cancer	0.08% 1/1263 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.16% 2/1254 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.16% 2/1262 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/1268 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer	0.55% 7/1263 • Number of events 7 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.88% 11/1254 • Number of events 11 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.55% 7/1262 • Number of events 8 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.39% 5/1268 • Number of events 5 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.16% 2/1263 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.24% 3/1254 • Number of events 3 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.40% 5/1262 • Number of events 5 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.39% 5/1268 • Number of events 5 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Other cancer	0.16% 2/1263 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/1254 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1262 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.24% 3/1268 • Number of events 3 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Other GI cancer	0.00% 0/1263 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1254 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/1262 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1268 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.08% 1/1263 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/1254 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/1262 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/1268 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic cancer	0.48% 6/1263 • Number of events 6 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.40% 5/1254 • Number of events 5 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.24% 3/1262 • Number of events 3 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.24% 3/1268 • Number of events 3 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.01% 1/7850 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	1.0% 13/1263 • Number of events 13 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	1.8% 22/1254 • Number of events 22 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	1.0% 13/1262 • Number of events 13 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	1.1% 14/1268 • Number of events 14 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin (melanoma) cancer	0.24% 3/1263 • Number of events 3 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.40% 5/1254 • Number of events 6 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.48% 6/1262 • Number of events 6 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.39% 5/1268 • Number of events 5 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Stomach cancer	0.08% 1/1263 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1254 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1262 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/1268 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.08% 1/1263 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.16% 2/1254 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.16% 2/1262 • Number of events 2 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.08% 1/1268 • Number of events 1 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.32% 4/1263 • Number of events 4 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.24% 3/1254 • Number of events 3 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.32% 4/1262 • Number of events 4 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.39% 5/1268 • Number of events 5 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Nervous system disorders Stroke	1.8% 23/1263 • Number of events 24 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	1.3% 16/1254 • Number of events 18 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	1.5% 19/1262 • Number of events 25 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	1.4% 18/1268 • Number of events 22 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Nervous system disorders Transient ischemic attack	0.32% 4/1263 • Number of events 4 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.64% 8/1254 • Number of events 8 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.40% 5/1262 • Number of events 6 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.39% 5/1268 • Number of events 5 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Surgical and medical procedures Coronary artery bypass graft (CABG)	1.3% 16/1263 • Number of events 16 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	1.6% 20/1254 • Number of events 21 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.87% 11/1262 • Number of events 11 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	2.0% 25/1268 • Number of events 25 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Surgical and medical procedures Interventional cardiology procedure	3.2% 40/1263 • Number of events 57 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	3.5% 44/1254 • Number of events 58 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	1.8% 23/1262 • Number of events 27 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	3.1% 39/1268 • Number of events 46 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.
Surgical and medical procedures Vascular/peripheral vascular intervention	1.0% 13/1263 • Number of events 14 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	1.1% 14/1254 • Number of events 17 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.63% 8/1262 • Number of events 16 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.55% 7/1268 • Number of events 9 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.	0.00% 0/7850 • Quarterly for 4 to 7 years During the 6 to 14 weeks before randomization, a run-in period was used to determine eligibility into the study. Randomization occurred after successful completion of the run-in period. Adverse events prior to randomization were not considered part of the study and are not reported here.

Other adverse events

Adverse event data not reported

Additional Information

GRADE Project Director

George Washington University

Phone: (301) 881-9260

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place