Trial Outcomes & Findings for The CANTATA-D2 Trial (CANagliflozin Treatment And Trial Analysis - DPP-4 Inhibitor Second Comparator Trial) (NCT NCT01137812)

NCT ID: NCT01137812

Last Updated: 2015-01-15

Results Overview

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 756 participants
• Primary outcome timeframe: Day 1 (Baseline) and Week 52
• Results posted on: 2015-01-15

Participant Flow

This study evaluated the efficacy and safety of canagliflozin compared with sitaglitin in patients with type 2 diabetes mellitus with inadequate control, despite treatment with metformin and sulphonylureas. The study was conducted between 30 June 2010 and 09 March 2012 and recruited patients from 140 study centers located in 17 countries worldwide.

A total of 756 patients were randomly allocated to the 2 treatment arms in the study. 755 patients received at least 1 dose of study drug and were included in the modified intent-to-treat (mITT) analysis set and the safety analysis set.

Participant milestones

Measure	Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.	Sitagliptin 100 mg Each patient received 100 mg of sitagliptin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Overall Study STARTED	377	378
Overall Study COMPLETED	254	210
Overall Study NOT COMPLETED	123	168

Reasons for withdrawal

Measure	Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.	Sitagliptin 100 mg Each patient received 100 mg of sitagliptin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Overall Study Adverse Event	21	14
Overall Study Lost to Follow-up	6	8
Overall Study Physician Decision	25	17
Overall Study Protocol Violation	5	4
Overall Study Withdrawal by Subject	5	13
Overall Study Death	2	0
Overall Study Patient met glycemic withdrawal criteria	40	85
Overall Study Other	19	27

Baseline Characteristics

The CANTATA-D2 Trial (CANagliflozin Treatment And Trial Analysis - DPP-4 Inhibitor Second Comparator Trial)

Baseline characteristics by cohort

Measure	Canagliflozin 300 mg n=377 Participants Each patient received 300 mg of canagliflozin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.	Sitagliptin 100 mg n=378 Participants Each patient received 100 mg of sitagliptin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.	Total n=755 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	304 Participants n=5 Participants	307 Participants n=7 Participants	611 Participants n=5 Participants
Age, Categorical >=65 years	73 Participants n=5 Participants	71 Participants n=7 Participants	144 Participants n=5 Participants
Age, Continuous	56.5 years STANDARD_DEVIATION 9.62 • n=5 Participants	56.6 years STANDARD_DEVIATION 9.33 • n=7 Participants	56.5 years STANDARD_DEVIATION 9.47 • n=5 Participants
Sex: Female, Male Female	170 Participants n=5 Participants	163 Participants n=7 Participants	333 Participants n=5 Participants
Sex: Female, Male Male	207 Participants n=5 Participants	215 Participants n=7 Participants	422 Participants n=5 Participants
Region Treated AUSTRIA	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
Region Treated BELGIUM	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region Treated BRAZIL	76 participants n=5 Participants	80 participants n=7 Participants	156 participants n=5 Participants
Region Treated CANADA	41 participants n=5 Participants	45 participants n=7 Participants	86 participants n=5 Participants
Region Treated DENMARK	2 participants n=5 Participants	5 participants n=7 Participants	7 participants n=5 Participants
Region Treated FRANCE	5 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants
Region Treated GERMANY	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Region Treated INDIA	33 participants n=5 Participants	23 participants n=7 Participants	56 participants n=5 Participants
Region Treated ISRAEL	7 participants n=5 Participants	3 participants n=7 Participants	10 participants n=5 Participants
Region Treated MALAYSIA	10 participants n=5 Participants	14 participants n=7 Participants	24 participants n=5 Participants
Region Treated NETHERLANDS	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region Treated NEW ZEALAND	11 participants n=5 Participants	13 participants n=7 Participants	24 participants n=5 Participants
Region Treated POLAND	20 participants n=5 Participants	25 participants n=7 Participants	45 participants n=5 Participants
Region Treated SINGAPORE	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region Treated SOUTH KOREA	7 participants n=5 Participants	12 participants n=7 Participants	19 participants n=5 Participants
Region Treated UKRAINE	27 participants n=5 Participants	19 participants n=7 Participants	46 participants n=5 Participants
Region Treated UNITED STATES	122 participants n=5 Participants	121 participants n=7 Participants	243 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 (Baseline) and Week 52

Population: This analysis used the modified intent-to-treat analysis set (all patients who were randomly assigned to a treatment group and received at least 1 dose of study drug). The last-observation-carried-forward method was applied when the Week 52 values were missing. The table includes only patients with both baseline and post baseline values.

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change.

Outcome measures

Measure	Canagliflozin 300 mg n=374 Participants Each patient received 300 mg of canagliflozin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.	Sitagliptin 100 mg n=365 Participants Each patient received 100 mg of sitagliptin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Change in HbA1c From Baseline to Week 52	-1.03 Percent Standard Error 0.048	-0.66 Percent Standard Error 0.049

SECONDARY outcome

Timeframe: Week 52

Population: This analysis used the modified intent-to-treat analysis set (all patients who were randomly assigned to a treatment group and received at least 1 dose of study drug). The last-observation-carried-forward method was applied when the Week 52 values were missing. The table includes only patients with both baseline and post baseline values.

The table below shows the percentage of patients with HbA1c <7% at Week 52 in each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the percentage.

Outcome measures

Measure	Canagliflozin 300 mg n=374 Participants Each patient received 300 mg of canagliflozin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.	Sitagliptin 100 mg n=365 Participants Each patient received 100 mg of sitagliptin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Percentage of Patients With HbA1c <7% at Week 52	47.6 Percentage of patients	35.3 Percentage of patients

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 52

Population: This analysis used the modified intent-to-treat analysis set (all patients who were randomly assigned to a treatment group and received at least 1 dose of study drug). The last-observation-carried-forward method was applied when the Week 52 values were missing. The table includes only patients with both baseline and post baseline values.

The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change.

Outcome measures

Measure	Canagliflozin 300 mg n=373 Participants Each patient received 300 mg of canagliflozin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.	Sitagliptin 100 mg n=365 Participants Each patient received 100 mg of sitagliptin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52	-29.9 mg/dL Standard Error 2.201	-5.85 mg/dL Standard Error 2.232

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 52

Population: This analysis used the modified intent-to-treat analysis set (all patients who were randomly assigned to a treatment group and received at least 1 dose of study drug). The last-observation-carried-forward method was applied when the Week 52 values were missing. The table includes only patients with both baseline and post baseline values.

The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean percent change.

Outcome measures

Measure	Canagliflozin 300 mg n=375 Participants Each patient received 300 mg of canagliflozin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.	Sitagliptin 100 mg n=367 Participants Each patient received 100 mg of sitagliptin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Percent Change in Body Weight From Baseline to Week 52	-2.5 Percent change Standard Error 0.2	0.3 Percent change Standard Error 0.2

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 52

Population: This analysis used the modified intent-to-treat analysis set (all patients who were randomly assigned to a treatment group and received at least 1 dose of study drug). The last-observation-carried-forward method was applied when the Week 52 values were missing. The table includes only patients with both baseline and post baseline values.

The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change.

Outcome measures

Measure	Canagliflozin 300 mg n=375 Participants Each patient received 300 mg of canagliflozin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.	Sitagliptin 100 mg n=367 Participants Each patient received 100 mg of sitagliptin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Change in Systolic Blood Pressure (SBP) From Baseline to Week 52	-5.06 mmHg Standard Error 0.656	0.85 mmHg Standard Error 0.666

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 52

Population: This analysis used the modified intent-to-treat analysis set (all patients who were randomly assigned to a treatment group and received at least 1 dose of study drug). The last-observation-carried-forward method was applied when the Week 52 values were missing. The table includes only patients with both baseline and post baseline values.

The table below shows the mean percent change in triglycerides from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change.

Outcome measures

Measure	Canagliflozin 300 mg n=365 Participants Each patient received 300 mg of canagliflozin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.	Sitagliptin 100 mg n=353 Participants Each patient received 100 mg of sitagliptin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Percent Change in Triglycerides From Baseline to Week 52	9.6 Percent change Standard Error 2.8	11.9 Percent change Standard Error 2.9

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 52

Population: This analysis used the modified intent-to-treat analysis set (all patients who were randomly assigned to a treatment group and received at least 1 dose of study drug). The last-observation-carried-forward method was applied when the Week 52 values were missing. The table includes only patients with both baseline and post baseline values.

The table below shows the mean percent change in HDL-C from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change.

Outcome measures

Measure	Canagliflozin 300 mg n=364 Participants Each patient received 300 mg of canagliflozin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.	Sitagliptin 100 mg n=353 Participants Each patient received 100 mg of sitagliptin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52	7.6 Percent change Standard Error 0.9	0.6 Percent change Standard Error 0.9

Adverse Events

Canagliflozin 300 mg

Serious events: 24 serious events

Other events: 157 other events

Deaths: 0 deaths

Sitagliptin 100 mg

Serious events: 21 serious events

Other events: 159 other events

Deaths: 0 deaths

Serious adverse events

Measure	Canagliflozin 300 mg n=377 participants at risk Each patient received 300 mg of canagliflozin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.	Sitagliptin 100 mg n=378 participants at risk Each patient received 100 mg of sitagliptin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Cardiac disorders Angina unstable	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Cardiac disorders Arteriosclerosis coronary artery	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Cardiac disorders Cardiac arrest	0.53% 2/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Cardiac disorders Coronary artery disease	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Cardiac disorders Ischaemic cardiomyopathy	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Cardiac disorders Myocardial infarction	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.53% 2/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Pancreatitis	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Hepatobiliary disorders Bile duct obstruction	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Hepatobiliary disorders Cholelithiasis	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Hepatobiliary disorders Gallbladder oedema	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Bronchopneumonia	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Leptospirosis	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Pneumonia	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.53% 2/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Pneumonia bacterial	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Pyelonephritis chronic	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Arthropod bite	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Contusion	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Hand fracture	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Hip fracture	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Incisional hernia, obstructive	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Meniscus lesion	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Splenic rupture	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Toxicity to various agents	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Wound	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Metabolism and nutrition disorders Obesity	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oropharyngeal cancer stage unspecified	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Cerebrovascular accident	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Cervical cord compression	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Convulsion	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Transient ischaemic attack	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Psychiatric disorders Suicide attempt	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Renal and urinary disorders Renal colic	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Reproductive system and breast disorders Vaginal haemorrhage	0.53% 2/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Skin and subcutaneous tissue disorders Leukocytoclastic vasculitis	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Vascular disorders Arterial thrombosis limb	0.27% 1/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Vascular disorders Arteriosclerosis	0.00% 0/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.26% 1/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.

Other adverse events

Measure	Canagliflozin 300 mg n=377 participants at risk Each patient received 300 mg of canagliflozin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.	Sitagliptin 100 mg n=378 participants at risk Each patient received 100 mg of sitagliptin once a day for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Infections and infestations Influenza	5.8% 22/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	4.0% 15/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Nasopharyngitis	8.8% 33/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	10.1% 38/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Upper respiratory tract infection	8.8% 33/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	5.6% 21/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Urinary tract infection	4.0% 15/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	5.0% 19/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Diarrhoea	4.5% 17/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.9% 26/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Metabolism and nutrition disorders Hypoglycaemia	17.5% 66/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	19.8% 75/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Headache	7.7% 29/377 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	7.1% 27/378 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.

Additional Information

Vice President, Franchise Medical Leader, Cardiovascular & Metabolism Franchise

Janssen Research & Development, LLC

Phone: 1-800-526-7736

Results disclosure agreements

• Principal investigator is a sponsor employee 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 in writing, such publication will be withheld for up to an additional 60 days.
• Publication restrictions are in place

Restriction type: OTHER