Trial Outcomes & Findings for Action to Control Cardiovascular Risk in Diabetes (ACCORD) (NCT NCT00000620)

Last Updated: 2016-11-22

Results Overview

Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. This was the primary outcome measure in all three trials: Glycemia (all participants), Blood Pressure (subgroup of participants not in Lipid Trial), and Lipid (subgroup of participants not in Blood Pressure Trial). In the Glycemia Trial, a finding of higher mortality in the intensive arm group led to an early discontinuation of therapy after a mean of 3.5 years of follow-up. Intensive arm participants were transitioned to standard arm strategy over a period of 0.2 year and followed for an additional 1.2 years to the planned end of the Glycemia Trial while participating in one of the other sub-trials (BP or Lipid) to their planned completion.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

10251 participants

Primary outcome timeframe

4.9 years

Results posted on

2016-11-22

Participant Flow

All participants had established type 2 diabetes and were recruited from 77 clinical centers in the United States (64 sites) and Canada (13 sites). Recruitment occurred in two phases, from January to June 2001 and from February 2003 to October 2005.

Eligible participants provided evidence of ability to routinely monitor capillary blood sugars from written records or electronic downloads from a self-monitoring blood glucose device (SMBG), or (in cases where such records could not be provided) underwent a 2 to 4-week pre-randomization run-in period to evaluate compliance with SMBG monitoring.

Participant milestones

Participant milestones
Measure	Glycemia Trial: Intensive Control/BP Trial: Intensive Control Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. BP Trial - Open label administration of anti-hypertensive agents to reduce and maintain systolic blood pressure (SBP) level to \<120 mmHg. Anti-hypertensive agents include multiple anti-hypertensive medications as needed to reach Blood Pressure Trial arm-specific goals.	Glycemia Trial: Intensive Control/BP Trial: Standard Control Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. BP Trial - Open label administration of multiple anti-hypertensive agents to maintain SBP level \<140 mm Hg. Anti-hypertensive agents include multiple anti-hypertensive medications as needed to reach Blood Pressure Trial arm-specific goals.	Glycemia Trial: Intensive Control/Lipid Trial: Fenofibrate Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. Lipid Trial - Double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m\^2 or 54 mg/day in patients with eGFR \<50 mL/min/1.73m\^2 in combination with open label simvastatin. Blinded fenofibrate or placebo plus simvastatin includes double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m\^2 or 54 mg/day in patients with eGFR \<50 mL/min/1.73m\^2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day.	Glycemia Trial: Intensive Control/Lipid Trial: Placebo Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. Double blind administration of placebo matching either 160 mg/day in participants with eGFR ≥50 mL/min/1.73m2 or 54 mg/day in participants with eGFR \<50 mL/min/1.73m\^2 in combination with open label simvastatin. Blinded fenofibrate or placebo plus simvastatin includes double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m\^2 or 54 mg/day in patients with eGFR \<50 mL/min/1.73m\^2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day.	Glycemia Trial: Standard Control/BP Trial: Intensive Control Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. BP Trial - Open label administration of anti-hypertensive agents to reduce and maintain systolic blood pressure (SBP) level to \<120 mmHg. Anti-hypertensive agents include multiple anti-hypertensive medications as needed to reach Blood Pressure Trial arm-specific goals.	Glycemia Trial: Standard Control/BP Trial: Standard Control Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. BP Trial - Open label administration of multiple anti-hypertensive agents to maintain SBP level \<140 mm Hg. Anti-hypertensive agents include multiple anti-hypertensive medications as needed to reach Blood Pressure Trial arm-specific goals (intensive control \<120 mm Hg; standard control \<140 mm Hg).	Glycemia Trial: Standard Control/Lipid Trial: Fenofibrate Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. Lipid Trial - Double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m\^2 or 54 mg/day in patients with eGFR \<50 mL/min/1.73m\^2 in combination with open label simvastatin. Blinded fenofibrate or placebo plus simvastatin includes double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m\^2 or 54 mg/day in patients with eGFR \<50 mL/min/1.73m\^2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day.	Glycemia Trial: Standard Control/Lipid Trial: Placebo Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. Double blind administration of placebo matching either 160 mg/day in participants with eGFR ≥50 mL/min/1.73m2 or 54 mg/day in participants with eGFR \<50 mL/min/1.73m\^2 in combination with open label simvastatin. Blinded fenofibrate or placebo plus simvastatin includes double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m\^2 or 54 mg/day in patients with eGFR \<50 mL/min/1.73m\^2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day.
Overall Study STARTED	1178	1193	1374	1383	1184	1178	1391	1370
Overall Study COMPLETED	1016	1057	1204	1205	1049	1026	1242	1224
Overall Study NOT COMPLETED	162	136	170	178	135	152	149	146

Reasons for withdrawal

Reasons for withdrawal
Measure	Glycemia Trial: Intensive Control/BP Trial: Intensive Control Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. BP Trial - Open label administration of anti-hypertensive agents to reduce and maintain systolic blood pressure (SBP) level to \<120 mmHg. Anti-hypertensive agents include multiple anti-hypertensive medications as needed to reach Blood Pressure Trial arm-specific goals.	Glycemia Trial: Intensive Control/BP Trial: Standard Control Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. BP Trial - Open label administration of multiple anti-hypertensive agents to maintain SBP level \<140 mm Hg. Anti-hypertensive agents include multiple anti-hypertensive medications as needed to reach Blood Pressure Trial arm-specific goals.	Glycemia Trial: Intensive Control/Lipid Trial: Fenofibrate Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. Lipid Trial - Double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m\^2 or 54 mg/day in patients with eGFR \<50 mL/min/1.73m\^2 in combination with open label simvastatin. Blinded fenofibrate or placebo plus simvastatin includes double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m\^2 or 54 mg/day in patients with eGFR \<50 mL/min/1.73m\^2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day.	Glycemia Trial: Intensive Control/Lipid Trial: Placebo Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. Double blind administration of placebo matching either 160 mg/day in participants with eGFR ≥50 mL/min/1.73m2 or 54 mg/day in participants with eGFR \<50 mL/min/1.73m\^2 in combination with open label simvastatin. Blinded fenofibrate or placebo plus simvastatin includes double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m\^2 or 54 mg/day in patients with eGFR \<50 mL/min/1.73m\^2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day.	Glycemia Trial: Standard Control/BP Trial: Intensive Control Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. BP Trial - Open label administration of anti-hypertensive agents to reduce and maintain systolic blood pressure (SBP) level to \<120 mmHg. Anti-hypertensive agents include multiple anti-hypertensive medications as needed to reach Blood Pressure Trial arm-specific goals.	Glycemia Trial: Standard Control/BP Trial: Standard Control Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. BP Trial - Open label administration of multiple anti-hypertensive agents to maintain SBP level \<140 mm Hg. Anti-hypertensive agents include multiple anti-hypertensive medications as needed to reach Blood Pressure Trial arm-specific goals (intensive control \<120 mm Hg; standard control \<140 mm Hg).	Glycemia Trial: Standard Control/Lipid Trial: Fenofibrate Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. Lipid Trial - Double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m\^2 or 54 mg/day in patients with eGFR \<50 mL/min/1.73m\^2 in combination with open label simvastatin. Blinded fenofibrate or placebo plus simvastatin includes double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m\^2 or 54 mg/day in patients with eGFR \<50 mL/min/1.73m\^2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day.	Glycemia Trial: Standard Control/Lipid Trial: Placebo Glycemia Trial - Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. Double blind administration of placebo matching either 160 mg/day in participants with eGFR ≥50 mL/min/1.73m2 or 54 mg/day in participants with eGFR \<50 mL/min/1.73m\^2 in combination with open label simvastatin. Blinded fenofibrate or placebo plus simvastatin includes double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m\^2 or 54 mg/day in patients with eGFR \<50 mL/min/1.73m\^2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day.
Overall Study Death	86	67	112	126	64	77	91	95
Overall Study Lost to Follow-up	14	14	14	14	15	15	13	14
Overall Study Withdrawal by Subject	40	27	28	27	30	32	32	21
Overall Study missed closeout visit	22	28	16	11	26	28	13	16

Baseline Characteristics

Action to Control Cardiovascular Risk in Diabetes (ACCORD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glycemia Trial: Intensive Control n=5128 Participants Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.	Glycemia Trial: Standard Control n=5123 Participants Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.	Total n=10251 Participants Total of all reporting groups
Age, Continuous	62.2 years STANDARD_DEVIATION 6.8 • n=5 Participants	62.2 years STANDARD_DEVIATION 6.8 • n=7 Participants	62.2 years STANDARD_DEVIATION 6.8 • n=5 Participants
Gender Female	1983 Participants n=5 Participants	1969 Participants n=7 Participants	3952 Participants n=5 Participants
Gender Male	3145 Participants n=5 Participants	3154 Participants n=7 Participants	6299 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	358 Participants n=5 Participants	379 Participants n=7 Participants	737 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4770 Participants n=5 Participants	4744 Participants n=7 Participants	9514 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Nonwhite	1828 participants n=5 Participants	1819 participants n=7 Participants	3647 participants n=5 Participants
Race/Ethnicity, Customized White	3300 participants n=5 Participants	3304 participants n=7 Participants	6604 participants n=5 Participants
Region of Enrollment United States	4376 participants n=5 Participants	4367 participants n=7 Participants	8743 participants n=5 Participants
Region of Enrollment Canada	752 participants n=5 Participants	756 participants n=7 Participants	1508 participants n=5 Participants
Previous cardiovascular disease (CVD) event History of CVD event	1827 participants n=5 Participants	1782 participants n=7 Participants	3609 participants n=5 Participants
Previous cardiovascular disease (CVD) event No history of CVD event	3301 participants n=5 Participants	3341 participants n=7 Participants	6642 participants n=5 Participants
Glycated hemoglobin	8.3 percent STANDARD_DEVIATION 1.1 • n=5 Participants	8.3 percent STANDARD_DEVIATION 1.1 • n=7 Participants	8.3 percent STANDARD_DEVIATION 1.1 • n=5 Participants
Blood pressure Systolic	136.2 mm Hg STANDARD_DEVIATION 17.0 • n=5 Participants	136.5 mm Hg STANDARD_DEVIATION 17.2 • n=7 Participants	136.4 mm Hg STANDARD_DEVIATION 17.1 • n=5 Participants
Blood pressure Diastolic	74.8 mm Hg STANDARD_DEVIATION 10.6 • n=5 Participants	75.0 mm Hg STANDARD_DEVIATION 10.7 • n=7 Participants	74.9 mm Hg STANDARD_DEVIATION 10.7 • n=5 Participants
Cholesterol LDL	104.9 mg/dL STANDARD_DEVIATION 34.0 • n=5 Participants	104.9 mg/dL STANDARD_DEVIATION 33.8 • n=7 Participants	104.9 mg/dL STANDARD_DEVIATION 33.9 • n=5 Participants
Cholesterol HDL	41.8 mg/dL STANDARD_DEVIATION 11.8 • n=5 Participants	41.9 mg/dL STANDARD_DEVIATION 11.5 • n=7 Participants	41.9 mg/dL STANDARD_DEVIATION 11.6 • n=5 Participants
Triglycerides	156 mg/dL n=5 Participants	154 mg/dL n=7 Participants	155 mg/dL n=5 Participants
Diabetes duration	10 years n=5 Participants	10 years n=7 Participants	10 years n=5 Participants

PRIMARY outcome

Timeframe: 4.9 years

Population: The population analyzed included all participants randomized and was performed by intention to treat with right-censoring of participants who did not complete follow-up prior to occurrence of MCE.

Outcome measures

Outcome measures
Measure	Glycemia Trial: Intensive Control n=5128 Participants Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.	Glycemia Trial: Standard Control n=5123 Participants Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.
First Occurrence of a Major Cardiovascular Event (MCE); Specifically Nonfatal Heart Attack, Nonfatal Stroke, or Cardiovascular Death (Measured Throughout the Study) in the Glycemia Trial.	503 participants	543 participants

PRIMARY outcome

Timeframe: 4.7 years

Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Primary outcome for Blood Pressure Trial.

Outcome measures

Outcome measures
Measure	Glycemia Trial: Intensive Control n=2363 Participants Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.	Glycemia Trial: Standard Control n=2371 Participants Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.
First Occurrence of Major Cardiovascular Event (MCE) in the Blood Pressure Trial.	208 participants	237 participants

PRIMARY outcome

Timeframe: 4.7 years

Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death in Lipid Trial participants.

Outcome measures

Outcome measures
Measure	Glycemia Trial: Intensive Control n=2765 Participants Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.	Glycemia Trial: Standard Control n=2753 Participants Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.
First Occurrence of Major Cardiovascular Event (MCE) in the Lipid Trial.	291 participants	310 participants

SECONDARY outcome

Timeframe: 4.9 years

Population: The population analyzed included all participants randomized and was performed by intention to treat with right-censoring of participants who did not complete follow-up prior to death.

Time to death from any cause. Secondary measure for Glycemia Trial. A finding of higher mortality in the intensive-therapy group led to an early discontinuation of therapy after a mean of 3.5 years of follow-up. Intensive arm participants were transitioned to standard arm strategy over a period of 0.2 year and followed for an additional 1.2 years to the planned end of the Glycemia Trial while participating in one of the other sub-trials (BP or Lipid).

Outcome measures

Outcome measures
Measure	Glycemia Trial: Intensive Control n=5128 Participants Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.	Glycemia Trial: Standard Control n=5123 Participants Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.
Death From Any Cause in the Glycemia Trial.	391 participants	327 participants

SECONDARY outcome

Timeframe: 4.7 years

Time to first occurrence of nonfatal or fatal stroke among participants in the BP Trial.

Outcome measures

Outcome measures
Measure	Glycemia Trial: Intensive Control n=2363 Participants Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.	Glycemia Trial: Standard Control n=2371 Participants Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.
Stroke in the Blood Pressure Trial.	36 participants	62 participants

SECONDARY outcome

Timeframe: 4.7 years

Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, cardiovascular death, revascularization procedure or hospitalization for CHF in Lipid Trial participants.

Outcome measures

Outcome measures
Measure	Glycemia Trial: Intensive Control n=2765 Participants Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.	Glycemia Trial: Standard Control n=2753 Participants Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.
First Occurrence of MCE or Revascularization or Hospitalization for Congestive Heart Failure (CHF) in Lipid Trial.	641 participants	667 participants

Adverse Events

Glycemia Trial: Intensive Control

Serious events: 137 serious events

Other events: 0 other events

Deaths: 0 deaths

Glycemia Trial: Standard Control

Serious events: 107 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Tim Craven / Senior Biostatistician

Wake Forest School of Medicine

Phone: 336-716-6109

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Glycemia Trial: Intensive Control n=5128 participants at risk Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels \<6.0%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.	Glycemia Trial: Standard Control n=5123 participants at risk Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.
Cardiac disorders Congestive heart failure	0.66% 34/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.23% 12/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Cardiac disorders Bradycardia, tachycardia, atrial fibrillation	0.25% 13/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.08% 4/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Cardiac disorders Angina/chest pain	0.08% 4/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.10% 5/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Cardiac disorders Myocardial infarction	0.08% 4/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.10% 5/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Vascular disorders Dizziness, hypotension, syncope	0.37% 19/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.33% 17/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Vascular disorders Edema	0.06% 3/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.02% 1/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Vascular disorders Cerebrovacular accident	0.02% 1/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.02% 1/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Gastrointestinal disorders Cholecystitis	0.10% 5/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.21% 11/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Gastrointestinal disorders Hepatitis/liver failure	0.04% 2/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.06% 3/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Gastrointestinal disorders Elevated creatinine, hyponatremia	0.04% 2/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.02% 1/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Gastrointestinal disorders Gastrointestinal bleeding	0.02% 1/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.02% 1/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Endocrine disorders Pancreatitis	0.10% 5/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.16% 8/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Endocrine disorders Ketoacidosis	0.02% 1/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.00% 0/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Endocrine disorders Hypoglycemia (fatal)	0.00% 0/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.02% 1/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Renal and urinary disorders Acute or chronic renal failure	0.16% 8/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.12% 6/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Immune system disorders Angioedema	0.18% 9/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.08% 4/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Immune system disorders Thrombocytopenia	0.04% 2/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.00% 0/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Immune system disorders Blood dyscrasia	0.02% 1/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.00% 0/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Immune system disorders Felodipine toxicity	0.02% 1/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.00% 0/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Musculoskeletal and connective tissue disorders Myositis	0.04% 2/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.06% 3/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Musculoskeletal and connective tissue disorders Rhabdomyolisis	0.02% 1/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.04% 2/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Musculoskeletal and connective tissue disorders Fractures	0.02% 1/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.04% 2/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Musculoskeletal and connective tissue disorders Weakness	0.00% 0/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.02% 1/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Eye disorders Macular edema	0.02% 1/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.02% 1/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Eye disorders Blurred vision	0.02% 1/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.02% 1/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Respiratory, thoracic and mediastinal disorders Shortness of breath	0.02% 1/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.00% 0/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
Injury, poisoning and procedural complications Motor vehicle accident (fatal)	0.06% 3/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.04% 2/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
General disorders Hyperkalemia	0.12% 6/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.10% 5/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
General disorders Hyponatremia	0.00% 0/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.08% 4/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
General disorders Severe fluid retention	0.06% 3/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.02% 1/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
General disorders Dehydration	0.02% 1/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.04% 2/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
General disorders Vertigo	0.00% 0/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.02% 1/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
General disorders Anemia	0.00% 0/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.02% 1/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
General disorders Hypomagnesemia	0.00% 0/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.02% 1/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
General disorders Hyperosmolar nonketotic coma	0.02% 1/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.00% 0/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
General disorders Toxic metabolic enecphalopathy	0.02% 1/5128 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.	0.00% 0/5123 • Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected. SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.