Trial Outcomes & Findings for CANVAS - CANagliflozin cardioVascular Assessment Study (NCT NCT01032629)

Last Updated: 2018-12-07

Results Overview

MACE, defined as a composite of CV death, non-fatal MI, and nonfatal stroke. Adjudication of these events by the Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of MACE are presented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

4330 participants

Primary outcome timeframe

Up to approximately 8 years

Results posted on

2018-12-07

Participant Flow

No Text enterred

Participant milestones

Participant milestones
Measure	Placebo Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 300 mg Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Overall Study STARTED	1442	1445	1443
Overall Study Treated	1441	1445	1441
Overall Study COMPLETED	1297	1344	1355
Overall Study NOT COMPLETED	145	101	88

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 300 mg Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Overall Study Closed Site	21	18	16
Overall Study Withdrawal by Subject	50	36	35
Overall Study Lost to Follow-up	74	47	37

Baseline Characteristics

CANVAS - CANagliflozin cardioVascular Assessment Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=1442 Participants Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg n=1445 Participants Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 300 mg n=1443 Participants Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.	Total n=4330 Participants Total of all reporting groups
Age, Continuous	62.3 Years STANDARD_DEVIATION 7.94 • n=93 Participants	62.2 Years STANDARD_DEVIATION 8 • n=4 Participants	62.8 Years STANDARD_DEVIATION 8.13 • n=27 Participants	62.4 Years STANDARD_DEVIATION 8.02 • n=483 Participants
Sex: Female, Male Female	486 Participants n=93 Participants	484 Participants n=4 Participants	499 Participants n=27 Participants	1469 Participants n=483 Participants
Sex: Female, Male Male	956 Participants n=93 Participants	961 Participants n=4 Participants	944 Participants n=27 Participants	2861 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	149 Participants n=93 Participants	142 Participants n=4 Participants	125 Participants n=27 Participants	416 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1288 Participants n=93 Participants	1300 Participants n=4 Participants	1317 Participants n=27 Participants	3905 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=93 Participants	3 Participants n=4 Participants	1 Participants n=27 Participants	9 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	5 Participants n=483 Participants
Race (NIH/OMB) Asian	262 Participants n=93 Participants	270 Participants n=4 Participants	263 Participants n=27 Participants	795 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants	6 Participants n=483 Participants
Race (NIH/OMB) Black or African American	35 Participants n=93 Participants	32 Participants n=4 Participants	38 Participants n=27 Participants	105 Participants n=483 Participants
Race (NIH/OMB) White	1064 Participants n=93 Participants	1060 Participants n=4 Participants	1055 Participants n=27 Participants	3179 Participants n=483 Participants
Race (NIH/OMB) More than one race	10 Participants n=93 Participants	8 Participants n=4 Participants	13 Participants n=27 Participants	31 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	67 Participants n=93 Participants	72 Participants n=4 Participants	70 Participants n=27 Participants	209 Participants n=483 Participants
Race/Ethnicity, Customized Asian	262 Participants n=93 Participants	270 Participants n=4 Participants	263 Participants n=27 Participants	795 Participants n=483 Participants
Race/Ethnicity, Customized Black or African American	35 Participants n=93 Participants	32 Participants n=4 Participants	38 Participants n=27 Participants	105 Participants n=483 Participants
Race/Ethnicity, Customized Hispanic or Latino	134 Participants n=93 Participants	123 Participants n=4 Participants	106 Participants n=27 Participants	363 Participants n=483 Participants
Race/Ethnicity, Customized Other	82 Participants n=93 Participants	86 Participants n=4 Participants	88 Participants n=27 Participants	256 Participants n=483 Participants
Race/Ethnicity, Customized White Non- Hispanic	929 Participants n=93 Participants	934 Participants n=4 Participants	948 Participants n=27 Participants	2811 Participants n=483 Participants
Region of Enrollment Argentina	57 Participants n=93 Participants	48 Participants n=4 Participants	55 Participants n=27 Participants	160 Participants n=483 Participants
Region of Enrollment Australia	57 Participants n=93 Participants	60 Participants n=4 Participants	60 Participants n=27 Participants	177 Participants n=483 Participants
Region of Enrollment Belgium	3 Participants n=93 Participants	10 Participants n=4 Participants	8 Participants n=27 Participants	21 Participants n=483 Participants
Region of Enrollment Canada	134 Participants n=93 Participants	139 Participants n=4 Participants	123 Participants n=27 Participants	396 Participants n=483 Participants
Region of Enrollment Colombia	4 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants	7 Participants n=483 Participants
Region of Enrollment Czech Republic	37 Participants n=93 Participants	37 Participants n=4 Participants	43 Participants n=27 Participants	117 Participants n=483 Participants
Region of Enrollment Estonia	19 Participants n=93 Participants	13 Participants n=4 Participants	12 Participants n=27 Participants	44 Participants n=483 Participants
Region of Enrollment Germany	47 Participants n=93 Participants	62 Participants n=4 Participants	66 Participants n=27 Participants	175 Participants n=483 Participants
Region of Enrollment Hungary	38 Participants n=93 Participants	50 Participants n=4 Participants	37 Participants n=27 Participants	125 Participants n=483 Participants
Region of Enrollment India	229 Participants n=93 Participants	232 Participants n=4 Participants	234 Participants n=27 Participants	695 Participants n=483 Participants
Region of Enrollment Israel	5 Participants n=93 Participants	11 Participants n=4 Participants	9 Participants n=27 Participants	25 Participants n=483 Participants
Region of Enrollment Luxembourg	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Region of Enrollment Malaysia	32 Participants n=93 Participants	24 Participants n=4 Participants	17 Participants n=27 Participants	73 Participants n=483 Participants
Region of Enrollment Mexico	40 Participants n=93 Participants	48 Participants n=4 Participants	36 Participants n=27 Participants	124 Participants n=483 Participants
Region of Enrollment Netherlands	70 Participants n=93 Participants	77 Participants n=4 Participants	81 Participants n=27 Participants	228 Participants n=483 Participants
Region of Enrollment New Zealand	27 Participants n=93 Participants	22 Participants n=4 Participants	25 Participants n=27 Participants	74 Participants n=483 Participants
Region of Enrollment Norway	41 Participants n=93 Participants	33 Participants n=4 Participants	35 Participants n=27 Participants	109 Participants n=483 Participants
Region of Enrollment Poland	47 Participants n=93 Participants	54 Participants n=4 Participants	43 Participants n=27 Participants	144 Participants n=483 Participants
Region of Enrollment Russia	146 Participants n=93 Participants	118 Participants n=4 Participants	125 Participants n=27 Participants	389 Participants n=483 Participants
Region of Enrollment Spain	64 Participants n=93 Participants	74 Participants n=4 Participants	71 Participants n=27 Participants	209 Participants n=483 Participants
Region of Enrollment Sweden	23 Participants n=93 Participants	26 Participants n=4 Participants	22 Participants n=27 Participants	71 Participants n=483 Participants
Region of Enrollment Ukraine	50 Participants n=93 Participants	39 Participants n=4 Participants	58 Participants n=27 Participants	147 Participants n=483 Participants
Region of Enrollment United Kingdom	31 Participants n=93 Participants	29 Participants n=4 Participants	32 Participants n=27 Participants	92 Participants n=483 Participants
Region of Enrollment United States	240 Participants n=93 Participants	238 Participants n=4 Participants	249 Participants n=27 Participants	727 Participants n=483 Participants

PRIMARY outcome

Timeframe: Up to approximately 8 years

Population: The primary analysis was based on the intent-to-treat (ITT) analysis set for adjudicated MACE, and included all randomized participants. As per planned analysis, the results were reported separately and combined for both doses.

Outcome measures

Outcome measures
Measure	Canagliflozin 300 mg n=1443 Participants Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.	Placebo n=1442 Participants Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg n=1445 Participants Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin (Total) n=2888 Participants Participants received one canagliflozin 100 mg or 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Major Adverse Cardiovascular Events (MACE) Composite of Cardiovascular (CV) Death, Non-Fatal Myocardial Infarction (MI), and Non-Fatal Stroke	25.37 Events per 1000 patient-year	30.36 Events per 1000 patient-year	28.41 Events per 1000 patient-year	26.89 Events per 1000 patient-year

SECONDARY outcome

Timeframe: Baseline and end of treatment (approximately 338 weeks)

Population: On-treatment analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) included subset of participants who were not receiving insulin at baseline and had at least one post-baseline HOMA2-%B measurement on-treatment prior to initiation of insulin.

The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-cell function. HOMA2-%B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady-state beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100 percent.

Outcome measures

Outcome measures
Measure	Canagliflozin 300 mg n=477 Participants Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.	Placebo n=463 Participants Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg n=511 Participants Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin (Total) Participants received one canagliflozin 100 mg or 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Change From Baseline in Homeostasis Model Assessment 2 Steady-State Beta-Cell Function (HOMA2-%B) at the End-of-Treatment (EOT)	8.09 Percentage of HOMA2 Standard Error 1.587	4.02 Percentage of HOMA2 Standard Error 1.611	6.82 Percentage of HOMA2 Standard Error 1.533	—

SECONDARY outcome

Timeframe: End of treatment (approximately 338 weeks)

Population: On-treatment analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies number of participants who were treated, had both baseline and post-baseline ACR measurements, and baseline ACR\<=300 mg/g.

Progression defined as the development of micro-albuminuria (albumin/creatinine ratio (ACR) greater than or equal to \[\>=\] 30 milligram per gram (mg/g) and less than or equal to \<= 300 mg/g) or macroalbuminuria (ACR of \>300 mg/g) in a participant with baseline normoalbuminuria or the development of macro-albuminuria in a participant with baseline microalbuminuria. Percentage of participants with progression of albuminuria at the end-of-treatment were assessed.

Outcome measures

Outcome measures
Measure	Canagliflozin 300 mg n=1298 Participants Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.	Placebo n=1286 Participants Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg n=1334 Participants Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin (Total) Participants received one canagliflozin 100 mg or 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Percentage of Participants With Progression of Albuminuria at the End-of-Treatment	18.3 Percentage of participants	24.0 Percentage of participants	20.2 Percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and end of treatment (approximately 338 weeks)

Population: On-treatment analysis set: all randomized participants who received at least 1 dose of study drug. 'N' (number of participants analyzed): number of participants evaluable for this outcome measure, had both baseline and any post-baseline PI/I ratio measurements on-treatment prior to initiation of insulin and didn't receive insulin through baseline.

A raised proinsulin-to-insulin ratio due to impaired processing of proinsulin is an early marker of beta cell dysfunction. Beta-cell dysfunction was evaluated by calculating the PI/I ratio, which estimates the capacity of beta cells to convert proinsulin to insulin and may represent an acceptable method to indicate the degree of beta-cell secretion.

Outcome measures

Outcome measures
Measure	Canagliflozin 300 mg n=412 Participants Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.	Placebo n=370 Participants Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg n=426 Participants Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin (Total) Participants received one canagliflozin 100 mg or 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Change From Baseline in Proinsulin/Insulin (PI/I) Ratio at the End-of-Treatment	1.03 Picomole per milli international units Standard Error 0.142	0.70 Picomole per milli international units Standard Error 0.150	0.67 Picomole per milli international units Standard Error 0.140	—

SECONDARY outcome

Timeframe: Baseline and End of treatment (approximately 338 weeks)

Population: On-treatment analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and had both baseline and post-baseline ACR measurements.

Urinary Albumin/Creatinine Ratio is a potential marker of chronic kidney disease, calculated as a ratio of Urinary Albumin and Urinary Creatinine.

Outcome measures

Outcome measures
Measure	Canagliflozin 300 mg n=1384 Participants Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.	Placebo n=1377 Participants Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg n=1398 Participants Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin (Total) Participants received one canagliflozin 100 mg or 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Change From Baseline in Urinary Albumin/Creatinine Ratio at End-of-Treatment	24.47 Milligram per gram (mg/g) Interval 23.11 to 25.91	29.30 Milligram per gram (mg/g) Interval 27.66 to 31.03	25.50 Milligram per gram (mg/g) Interval 24.09 to 27.0	—

SECONDARY outcome

Timeframe: Baseline and end of treatment (approximately 338 weeks)

Population: On-treatment analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure who had both baseline and post-baseline eGFR measurements.

Change from baseline in Estimated Glomerular Filtration Rate (eGFR) was assessed at end of treatment. GFR is a measure of the rate at which blood is filtered by the kidney. Modification of Diet in Renal Disease (MDRD) is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine, age, race, and sex. eGFR milliliters/minute/1.73 meters square (mL/min/1.73 m\^2) = 175 \* (serum creatinine) \^ 1.154 \* (Age) \^-0.203 \*(0.742 if female) \* (1.21 if Black).

Outcome measures

Outcome measures
Measure	Canagliflozin 300 mg n=1383 Participants Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.	Placebo n=1394 Participants Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg n=1412 Participants Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin (Total) Participants received one canagliflozin 100 mg or 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at End-of-Treatment	-3.98 mL/min/1.73 m^2 Standard Error 0.392	-5.23 mL/min/1.73 m^2 Standard Error 0.390	-3.55 mL/min/1.73 m^2 Standard Error 0.388	—

SECONDARY outcome

Timeframe: Baseline and end of treatment (approximately 338 weeks)

Population: On-treatment analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure who had both baseline and any post-baseline HbA1C measurements.

Change from baseline in glycated hemoglobin (HbA1c) percentage (%) was assessed at end of treatment. Glycated hemoglobin is a form of hemoglobin that is measured primarily to identify the average glucose concentration in the blood.

Outcome measures

Outcome measures
Measure	Canagliflozin 300 mg n=1352 Participants Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.	Placebo n=1366 Participants Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg n=1392 Participants Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin (Total) Participants received one canagliflozin 100 mg or 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Change From Baseline in Glycated Hemoglobin (HbA1c) at End-of-Treatment	-0.31 HbA1c (%) Standard Error 0.032	0.01 HbA1c (%) Standard Error 0.032	-0.26 HbA1c (%) Standard Error 0.032	—

SECONDARY outcome

Timeframe: Baseline and end of treatment (approximately 338 weeks)

Population: On-treatment analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and had both baseline and post-baseline fasting plasma glucose measurements.

Change from baseline in the fasting plasma glucose levels at end-of-treatment was assessed.

Outcome measures

Outcome measures
Measure	Canagliflozin 300 mg n=1377 Participants Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.	Placebo n=1392 Participants Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg n=1410 Participants Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin (Total) Participants received one canagliflozin 100 mg or 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Change From Baseline in Fasting Plasma Glucose (FPG) Levels at End-of-Treatment	-0.57 Millimoles per liter (mmol/L) Standard Error 0.076	0.16 Millimoles per liter (mmol/L) Standard Error 0.076	-0.42 Millimoles per liter (mmol/L) Standard Error 0.075	—

SECONDARY outcome

Timeframe: Baseline and end of treatment (approximately 338 weeks)

Population: On-treatment analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and who had both baseline and post-baseline body weight.

Percent change from baseline in body weight was assessed at the end of treatment.

Outcome measures

Outcome measures
Measure	Canagliflozin 300 mg n=1388 Participants Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.	Placebo n=1398 Participants Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg n=1415 Participants Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin (Total) Participants received one canagliflozin 100 mg or 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Percent Change From Baseline in Body Weight at End-of-Treatment	-4.12 Percent change Standard Error 0.185	-0.50 Percent change Standard Error 0.184	-3.47 Percent change Standard Error 0.183	—

SECONDARY outcome

Timeframe: Baseline and end of treatment (approximately 338 weeks)

Population: On-treatment analysis set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure who and had both baseline and post-baseline blood pressure measurements.

Change from baseline in systolic blood pressure and diastolic blood pressure was assessed.

Outcome measures

Outcome measures
Measure	Canagliflozin 300 mg n=1388 Participants Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.	Placebo n=1398 Participants Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg n=1415 Participants Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin (Total) Participants received one canagliflozin 100 mg or 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at End-of-Treatment SBP(Change at end of treatment)	-6.49 Millimeter of mercury (mmHg) Standard Error 0.378	-1.96 Millimeter of mercury (mmHg) Standard Error 0.377	-4.91 Millimeter of mercury (mmHg) Standard Error 0.375	—
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at End-of-Treatment DBP (Change at end of treatment)	-4.51 Millimeter of mercury (mmHg) Standard Error 0.223	-2.88 Millimeter of mercury (mmHg) Standard Error 0.223	-3.70 Millimeter of mercury (mmHg) Standard Error 0.221	—

SECONDARY outcome

Timeframe: Baseline and end of treatment (approximately 338 weeks)

Population: On-treatment set included all randomized participants who received at least 1 dose of study drug. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and who had both baseline and post-baseline lipid measurements.

Change from baseline in triglycerides levels was assessed.

Outcome measures

Outcome measures
Measure	Canagliflozin 300 mg n=1321 Participants Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.	Placebo n=1325 Participants Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg n=1371 Participants Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin (Total) Participants received one canagliflozin 100 mg or 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Change From Baseline in Triglycerides Levels at End-of-Treatment	0.09 mmol/L Standard Deviation 1.238	0.05 mmol/L Standard Deviation 1.597	0.13 mmol/L Standard Deviation 1.679	—

SECONDARY outcome

Timeframe: Baseline and end of treatment (approximately 338 weeks)

Change from baseline in cholesterol, high-density lipoprotein cholesterol and low density lipoprotein cholesterol levels were assessed.

Outcome measures

Outcome measures
Measure	Canagliflozin 300 mg n=1321 Participants Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.	Placebo n=1325 Participants Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg n=1371 Participants Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin (Total) Participants received one canagliflozin 100 mg or 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Change From Baseline in Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) Levels at End-of-Treatment Cholesterol (change at EOT)	0.16 mmol/L Standard Error 0.028	-0.07 mmol/L Standard Error 0.028	0.11 mmol/L Standard Error 0.027	—
Change From Baseline in Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) Levels at End-of-Treatment HDL-C (change at EOT)	0.05 mmol/L Standard Error 0.006	-0.01 mmol/L Standard Error 0.006	0.04 mmol/L Standard Error 0.006	—
Change From Baseline in Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) Levels at End-of-Treatment LDL-C (change at EOT)	0.10 mmol/L Standard Error 0.023	-0.07 mmol/L Standard Error 0.022	0.04 mmol/L Standard Error 0.022	—

SECONDARY outcome

Timeframe: Baseline and end of treatment (approximately 338 weeks)

Change from baseline in LDL-C to HDL-C ratio was assessed.

Outcome measures

Outcome measures
Measure	Canagliflozin 300 mg n=1321 Participants Participants received one canagliflozin 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.	Placebo n=1325 Participants Participants received one placebo capsule orally once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin 100 mg n=1371 Participants Participants received one canagliflozin 100 milligram (mg) capsule once daily for the duration of the study or until early discontinuation from treatment.	Canagliflozin (Total) Participants received one canagliflozin 100 mg or 300 mg capsule once daily for the duration of the study or until early discontinuation from treatment.
Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) to High-Density Lipoprotein-Cholesterol (HDL-C) Ratio at End-of-Treatment	0.00 Ratio Standard Error 0.021	-0.04 Ratio Standard Error 0.021	-0.02 Ratio Standard Error 0.021	—

Adverse Events

Placebo

Serious events: 584 serious events

Other events: 1137 other events

Deaths: 74 deaths

Canagliflozin 100 mg

Serious events: 601 serious events

Other events: 1146 other events

Deaths: 68 deaths

Canagliflozin 300 mg

Serious events: 606 serious events

Other events: 1167 other events

Deaths: 66 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Director Clinical Leader

Janssen- Cilag International NV

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER