The CANTATA-D Trial (CANagliflozin Treatment and Trial Analysis - DPP-4 Inhibitor Comparator Trial)

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01106677
• Collaborator: (none)
• Enrollment: 1,284
• Locations: 128
• Arms: 4
• Duration (Months): 24
• Patients Per Site: 10
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of canagliflozin compared with sitagliptin and placebo in patients with type 2 diabetes mellitus who are receiving treatment with metformin monotherapy (i.e., treatment with a single drug) and have inadequate glycemic (blood sugar) control.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Placebo; Drug: Canagliflozin; Drug: Sitagliptin; Drug: Metformin immediate release	Phase 3

Detailed Description

Canagliflozin is a drug that is being tested to see if it may be useful in treating patients diagnosed with type 2 diabetes mellitus (T2DM). This is a randomized (study drug assigned by chance), double-blind (neither the patient nor the study doctor will know the identity of assigned study drug), placebo- and active-controlled, parallel-group, 4-arm (4 treatment groups) multicenter study to determine the efficacy, safety, and tolerability of canagliflozin (100 mg and 300 mg) compared to placebo (a capsule that looks like all the other treatments but has no real medicine) and an active-control (sitagliptin 100 mg, an antihyperglycemic agent) in patients with T2DM who are not achieving an adequate response from current antihyperglycemic therapy with metformin Immediate Release (IR) to control their diabetes. Approximately 1,260 patients with T2DM who are receiving treatment with metformin IR and have inadequate glycemic (blood sugar) will receive once-daily treatment with canagliflozin (100 mg or 300 mg), sitagliptin 100 mg, or placebo capsules for 26 weeks (Period I) followed by another 26-weeks where patients treated with canagliflozin (100 mg or 300 mg) or sitagliptin 100 mg will continue treatment for an additional 26 weeks and patients treated with placebo will be switched to active double-blind treatment with sitagliptin 100 mg capsules administered once-daily for 26 weeks (Period II). In addition, all patients will take protocol specified stable doses of metformin IR along with assigned study drug for the duration of the study. Patients will participate in the study for approximately 59 to 71 weeks. During the study, if a patient's fasting blood sugar remains high despite treatment with study drug, metformin IR, and reinforcement with diet and exercise, the patient will receive treatment with glimepiride (rescue therapy) consistent with local prescribing information. During treatment, patients will be monitored for safety by review of adverse events, results from laboratory tests, 12-lead electrocardiograms (ECGs), vital sign measurements, body weight, physical examinations, and self-monitored blood glucose (SMGB) measurements. The primary outcome measure in the study is to assess the effect of canagliflozin relative to placebo on hemoglobin A1c (HbA1c) after 26 weeks of treatment. Study drug will be taken orally (by mouth) once daily before the first meal each day unless otherwise specified. Patients will take single-blind placebo for 2 weeks before randomization. After randomization, patients in the study will take double-blind canagliflozin (100 mg or 300 mg) or sitagliptin 100 mg for 52 weeks OR placebo for 26 weeks switched to double-blind treatment with sitaliptin 100 mg for 26 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1284 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo and Active-Controlled, 4-Arm, Parallel Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin in the Treatment of Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Canagliflozin 100 mg Each patient will receive 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Drug: Canagliflozin; One 100 mg or 300 mg over-encapsulated tablet orally once daily for 52 weeks with protocol-specified doses of metformin immediate release.; Drug: Metformin immediate release; The patient's stable dose of metformin immediate release background therapy should be continued throughout the study.
Experimental: Canagliflozin 300 mg Each patient will receive 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Drug: Canagliflozin; One 100 mg or 300 mg over-encapsulated tablet orally once daily for 52 weeks with protocol-specified doses of metformin immediate release.; Drug: Metformin immediate release; The patient's stable dose of metformin immediate release background therapy should be continued throughout the study.
Active Comparator: Sitagliptin 100 mg Each patient will receive 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Drug: Sitagliptin; One 100 mg over-encapsulated tablet orally once daily for 52 weeks (sitagliptin 100 mg arm) or once daily beginning at Week 26 until Week 52 (placebo/sitagliptin arm). Sitagliptin will be given with protocol-specified doses of metformin immediate release.; Drug: Metformin immediate release; The patient's stable dose of metformin immediate release background therapy should be continued throughout the study.
Other: Placebo/Sitagliptin Each patient will receive matching placebo once daily for 26 weeks and will then switch from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin will be given with protocol-specified doses of metformin immediate release.	Drug: Placebo; One matching placebo capsule orally (by mouth) once daily for 26 weeks with protocol-specified doses of metformin immediate release.; Drug: Sitagliptin; One 100 mg over-encapsulated tablet orally once daily for 52 weeks (sitagliptin 100 mg arm) or once daily beginning at Week 26 until Week 52 (placebo/sitagliptin arm). Sitagliptin will be given with protocol-specified doses of metformin immediate release.; Drug: Metformin immediate release; The patient's stable dose of metformin immediate release background therapy should be continued throughout the study.

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c From Baseline to Week 26 [Day 1 (Baseline) and Week 26]

   The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change.

Secondary Outcome Measures

1. Percentage of Patients With HbA1c <7% at Week 26 [Week 26]

   The table below shows the percentage of patients with HbA1c <7% at Week 26 in each treatment group. The statistical analyses show the treatment differences between each canagliflozin or sitagliptin group and placebo.

2. Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 [Day 1 (Baseline) and Week 26]

   The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change.

3. Change in 2-hour Post-prandial Glucose From Baseline to Week 26 [Day 1 (Baseline) and Week 26]

   The table below shows the least-squares (LS) mean change in 2-hour post-prandial glucose from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change.

4. Percent Change in Body Weight From Baseline to Week 26 [Day 1 (Baseline) and Week 26]

   The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change.

5. Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 [Day 1 (Baseline) and Week 26]

   The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change.

6. Percent Change in Triglycerides From Baseline to Week 26 [Day 1 (Baseline) and Week 26]

   The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change.

7. Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 [Day 1 (Baseline) and Week 26]

   The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change.

8. Change in HbA1c From Baseline to Week 52 [Day 1 (Baseline) and Week 52]

   The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change.

9. Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52 [Day 1 (Baseline) and Week 52]

   The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change.

10. Percent Change in Body Weight From Baseline to Week 52 [Day 1 (Baseline) and Week 52]

    The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change.

11. Change in Systolic Blood Pressure (SBP) From Baseline to Week 52 [Day 1 (Baseline) and Week 52]

    The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change.

12. Percent Change in Triglycerides From Baseline to Week 52 [Day 1 (Baseline) and Week 52]

    The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change.

13. Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 [Day 1 (Baseline) and Week 52]

    The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All patients must have a diagnosis of T2DM and be currently treated with metformin IR

• Patients in the study must have a HbA1c between >=7 and <=10.5%

• Patients must have a fasting plasma glucose (FPG) <270 mg/dL (15 mmol/L)

Exclusion Criteria:

• History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, diabetes secondary to pancreatitis or pancreatectomy, or a severe hypoglycemic episode within 6 months before screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Little Rock	Arkansas	United States
2		Fountain Valley	California	United States
3		National City	California	United States
4		Northridge	California	United States
5		Colorado Springs	Colorado	United States
6		Denver	Colorado	United States
7		Bradenton	Florida	United States
8		Brooksville	Florida	United States
9		Defuniak Springs	Florida	United States
10		Hialeah	Florida	United States
11		Niceville	Florida	United States
12		Tampa	Florida	United States
13		Atlanta	Georgia	United States
14		Savannah	Georgia	United States
15		Champaign	Illinois	United States
16		Avon	Indiana	United States
17		Fishers	Indiana	United States
18		Franklin	Indiana	United States
19		West Des Moines	Iowa	United States
20		Wichita	Kansas	United States
21		Munfordville	Kentucky	United States
22		Portland	Maine	United States
23		Benzonia	Michigan	United States
24		Interlochen	Michigan	United States
25		Troy	Michigan	United States
26		Picayune	Mississippi	United States
27		Florissant	Missouri	United States
28		Saint Louis	Missouri	United States
29		Las Vegas	Nevada	United States
30		Mansfield	New Jersey	United States
31		New Hyde Park	New York	United States
32		Asheboro	North Carolina	United States
33		Charlotte	North Carolina	United States
34		Kettering	Ohio	United States
35		Oregon City	Oregon	United States
36		Altoona	Pennsylvania	United States
37		Tipton	Pennsylvania	United States
38		East Providence	Rhode Island	United States
39		Greer	South Carolina	United States
40		Mount Pleasant	South Carolina	United States
41		Nashville	Tennessee	United States
42		New Braunfels	Texas	United States
43		San Antonio	Texas	United States
44		Bountiful	Utah	United States
45		Spokane	Washington	United States
46		Buenos Aires		Argentina
47		Mendoza		Argentina
48		San Juan		Argentina
49		Pleven		Bulgaria
50		Plovdiv		Bulgaria
51		Sevlievo		Bulgaria
52		Sofia		Bulgaria
53		Barranquilla		Colombia
54		Bogota		Colombia
55		Medellin		Colombia
56		Beroun		Czech Republic
57		Pardubice		Czech Republic
58		Plzen		Czech Republic
59		Rychnov Nad Kneznou		Czech Republic
60		Tabor		Czech Republic
61		Tallinn		Estonia
62		Piraeus		Greece
63		Thessalonikis		Greece
64		Ahmedabad, Gujarat		India
65		Aurangabad		India
66		Bangalore, Karnataka		India
67		Bangalore		India
68		Belgaum		India
69		Coimbatore		India
70		Mumbai		India
71		Nagpur		India
72		Pune		India
73		Trivandrum		India
74		Daugavpils		Latvia
75		Limbazi		Latvia
76		Riga		Latvia
77		Talsi		Latvia
78		Kelantan		Malaysia
79		Kuala Lumpur N/A		Malaysia
80		Kuala Lumpur		Malaysia
81		Pulau Pinang		Malaysia
82		Selangor		Malaysia
83		Culiacan		Mexico
84		Guadalajara		Mexico
85		Monterrey		Mexico
86		Queretaro		Mexico
87		Tampico		Mexico
88		Lima 1 Lima Lima		Peru
89		Leczyca		Poland
90		Lodz		Poland
91		Lublin		Poland
92		Wroclaw		Poland
93		Zgierz		Poland
94		Aveiro		Portugal
95		Leiria		Portugal
96		Lisboa		Portugal
97		Portalegre		Portugal
98		San Juan		Puerto Rico
99		Chelyabinsk		Russian Federation
100		Dzerzhinsky Moscow Region		Russian Federation
101		Ekaterinburg		Russian Federation
102		Kemerovo		Russian Federation
103		Penza		Russian Federation
104		Saint Petersburg		Russian Federation
105		St Petersburg		Russian Federation
106		St-Petersburg		Russian Federation
107		Singapore		Singapore
108		Banska Bystrica		Slovakia
109		Bratislava		Slovakia
110		Kosice		Slovakia
111		Sahy		Slovakia
112		Trebisov		Slovakia
113		Göteborg		Sweden
114		Stockholm		Sweden
115		Bangkok		Thailand
116		Chiang Mai		Thailand
117		Khon Kaen		Thailand
118		Ankara		Turkey
119		Antalya		Turkey
120		Istanbul		Turkey
121		Izmir		Turkey
122		Konya		Turkey
123		Donetsk		Ukraine
124		Ivano Frankivsk		Ukraine
125		Kiev		Ukraine
126		Sumy		Ukraine
127		Vinnitsa		Ukraine
128		Zaporozhye		Ukraine

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT01106677
• Other Study ID Numbers: CR017023; 28431754DIA3006
• First Posted: Apr 20, 2010
• Last Update Posted: Jul 30, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by Janssen Research & Development, LLC: Type 2 diabetes mellitus; Canagliflozin; Placebo; Sitagliptin; Januvia; Metformin Immediate Release (IR); Hemoglobin A1c
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Metformin; Sitagliptin Phosphate; Canagliflozin

Study Results

Participant Flow

Recruitment Details	This study evaluated the efficacy and safety of canagliflozin compared with sitagliptin and placebo in patients with type 2 diabetes mellitus with inadequate control despite treatment with metformin. The study was conducted between 07 April 2010 and 17 August 2012 and recruited patients from 169 study centers in 22 countries worldwide.
Pre-assignment Detail	1,284 patients were randomly allocated to the 4 treatment arms. All patients received at least 1 dose of study drug and were included in the modified intent-to-treat (mITT) analysis set (used for the Week 26 and week 52 efficacy analyses). All 1,284 patients were included in the Week 26 and Week 52 safety analysis sets.

Arm/Group Title	Placebo/Sitagliptin	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Period Title: Core Period: Baseline to Week 26
STARTED	183	368	367	366
COMPLETED	155	322	323	319
NOT COMPLETED	28	46	44	47
Period Title: Core Period: Baseline to Week 26
STARTED	153	316	321	313
COMPLETED	138	298	299	285
NOT COMPLETED	15	18	22	28

Baseline Characteristics

Arm/Group Title	Placebo/Sitagliptin	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg	Total
Arm/Group Description	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Total of all reporting groups
Overall Participants	183	368	367	366	1284
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	146 79.8%	314 85.3%	309 84.2%	309 84.4%	1078 84%
>=65 years	37 20.2%	54 14.7%	58 15.8%	57 15.6%	206 16%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.3 (9.76)	55.5 (9.38)	55.3 (9.19)	55.5 (9.55)	55.4 (9.42)
Sex: Female, Male (Count of Participants)
Female	89 48.6%	194 52.7%	202 55%	194 53%	679 52.9%
Male	94 51.4%	174 47.3%	165 45%	172 47%	605 47.1%
Region Enroll (participants) [Number]
ARGENTINA	8 4.4%	9 2.4%	15 4.1%	11 3%	43 3.3%
BULGARIA	4 2.2%	2 0.5%	1 0.3%	3 0.8%	10 0.8%
COLOMBIA	4 2.2%	15 4.1%	8 2.2%	15 4.1%	42 3.3%
CZECH REPUBLIC	7 3.8%	8 2.2%	8 2.2%	7 1.9%	30 2.3%
ESTONIA	6 3.3%	6 1.6%	3 0.8%	5 1.4%	20 1.6%
GREECE	1 0.5%	1 0.3%	3 0.8%	4 1.1%	9 0.7%
INDIA	13 7.1%	28 7.6%	31 8.4%	22 6%	94 7.3%
ITALY	2 1.1%	3 0.8%	3 0.8%	1 0.3%	9 0.7%
LATVIA	3 1.6%	7 1.9%	6 1.6%	10 2.7%	26 2%
MALAYSIA	9 4.9%	7 1.9%	11 3%	7 1.9%	34 2.6%
MEXICO	12 6.6%	20 5.4%	26 7.1%	18 4.9%	76 5.9%
PERU	16 8.7%	36 9.8%	30 8.2%	37 10.1%	119 9.3%
POLAND	1 0.5%	18 4.9%	14 3.8%	10 2.7%	43 3.3%
PORTUGAL	1 0.5%	1 0.3%	0 0%	2 0.5%	4 0.3%
RUSSIAN FEDERATION	15 8.2%	34 9.2%	28 7.6%	22 6%	99 7.7%
SINGAPORE	3 1.6%	5 1.4%	3 0.8%	3 0.8%	14 1.1%
SLOVAKIA	12 6.6%	16 4.3%	21 5.7%	17 4.6%	66 5.1%
SWEDEN	3 1.6%	3 0.8%	2 0.5%	4 1.1%	12 0.9%
THAILAND	4 2.2%	9 2.4%	11 3%	8 2.2%	32 2.5%
TURKEY	1 0.5%	5 1.4%	11 3%	9 2.5%	26 2%
UKRAINE	8 4.4%	24 6.5%	29 7.9%	30 8.2%	91 7.1%
UNITED STATES	50 27.3%	111 30.2%	103 28.1%	121 33.1%	385 30%

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c From Baseline to Week 26
Description	The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change.
Time Frame	Day 1 (Baseline) and Week 26

Outcome Measure Data

Analysis Population Description

Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Arm/Group Title	Placebo/Sitagliptin	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Measure Participants	181	365	360	354
Least Squares Mean (Standard Error) [Percent]	-0.17 (0.060)	-0.79 (0.044)	-0.94 (0.044)	-0.82 (0.044)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 100 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculation: assuming a difference between canagliflozin and placebo of 0.5% and a common standard deviation of 1.0%, and using a 2-sample, 1-sided t-test with a Type I error rate of 0.05, it was estimated that 86 subjects per group would provide 90% power to demonstrate superiority of canagliflozin over placebo.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-0.62
	Confidence Interval	(2-Sided) 95%; -0.758 to -0.481
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.071
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Power calculation: assuming a difference between canagliflozin and placebo of 0.5% and a common standard deviation of 1.0%, and using a 2-sample, 1-sided t-test with a Type I error rate of 0.05, it was estimated that 86 subjects per group would provide 90% power to demonstrate superiority of canagliflozin over placebo.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-0.77
	Confidence Interval	(2-Sided) 95%; -0.914 to -0.636
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.071
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Sitagliptin 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-0.66
	Confidence Interval	(2-Sided) 95%; -0.795 to -0.516
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.071
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Patients With HbA1c <7% at Week 26
Description	The table below shows the percentage of patients with HbA1c <7% at Week 26 in each treatment group. The statistical analyses show the treatment differences between each canagliflozin or sitagliptin group and placebo.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Arm/Group Title	Placebo/Sitagliptin	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Measure Participants	181	365	360	354
Number [Percentage of patients]	29.8	45.5	57.8	54.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.29
	Confidence Interval	(2-Sided) 95%; 1.50 to 3.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.39
	Confidence Interval	(2-Sided) 95%; 2.85 to 6.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26
Description	The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change.
Time Frame	Day 1 (Baseline) and Week 26

Outcome Measure Data

Analysis Population Description

Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Arm/Group Title	Placebo/Sitagliptin	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Measure Participants	181	365	360	354
Least Squares Mean (Standard Error) [mg/dL]	2.47 (2.576)	-27.3 (1.873)	-37.8 (1.893)	-20.2 (1.908)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-29.8
	Confidence Interval	(2-Sided) 95%; -35.76 to -23.81
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.044
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-40.3
	Confidence Interval	(2-Sided) 95%; -46.25 to -34.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.055
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Sitagliptin 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-22.7
	Confidence Interval	(2-Sided) 95%; -28.70 to -16.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.060
	Estimation Comments

4. Secondary Outcome

Title	Change in 2-hour Post-prandial Glucose From Baseline to Week 26
Description	The table below shows the least-squares (LS) mean change in 2-hour post-prandial glucose from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change.
Time Frame	Day 1 (Baseline) and Week 26

Outcome Measure Data

Analysis Population Description

Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Arm/Group Title	Placebo/Sitagliptin	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Measure Participants	129	298	288	295
Least Squares Mean (Standard Error) [mg/dL]	-9.79 (4.860)	-47.9 (3.305)	-57.1 (3.356)	-49.3 (3.340)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-38.1
	Confidence Interval	(2-Sided) 95%; -49.14 to -27.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.601
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-47.3
	Confidence Interval	(2-Sided) 95%; -58.40 to -36.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.635
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Sitagliptin 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-39.6
	Confidence Interval	(2-Sided) 95%; -50.56 to -28.55
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.608
	Estimation Comments

5. Secondary Outcome

Title	Percent Change in Body Weight From Baseline to Week 26
Description	The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change.
Time Frame	Day 1 (Baseline) and Week 26

Outcome Measure Data

Analysis Population Description

Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Arm/Group Title	Placebo/Sitagliptin	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Measure Participants	181	365	360	355
Least Squares Mean (Standard Error) [Percent change]	-1.2 (0.3)	-3.7 (0.2)	-4.2 (0.2)	-1.2 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -3.1 to -1.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -3.5 to -2.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Sitagliptin 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

6. Secondary Outcome

Title	Change in Systolic Blood Pressure (SBP) From Baseline to Week 26
Description	The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change.
Time Frame	Day 1 (Baseline) and Week 26

Outcome Measure Data

Analysis Population Description

Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Arm/Group Title	Placebo/Sitagliptin	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Measure Participants	181	365	360	355
Least Squares Mean (Standard Error) [mmHg]	1.52 (0.829)	-3.84 (0.602)	-5.06 (0.605)	-1.83 (0.611)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-5.36
	Confidence Interval	(2-Sided) 95%; -7.280 to -3.439
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.979
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-6.58
	Confidence Interval	(2-Sided) 95%; -8.504 to -4.653
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.981
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Sitagliptin 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-3.34
	Confidence Interval	(2-Sided) 95%; -5.273 to -1.413
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.984
	Estimation Comments

7. Secondary Outcome

Title	Percent Change in Triglycerides From Baseline to Week 26
Description	The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change.
Time Frame	Day 1 (Baseline) and Week 26

Outcome Measure Data

Analysis Population Description

Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Arm/Group Title	Placebo/Sitagliptin	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Measure Participants	171	358	341	338
Least Squares Mean (Standard Error) [Percent change]	3.2 (3.6)	1.6 (2.6)	-1.4 (2.6)	1.0 (2.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.702
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-1.6
	Confidence Interval	() 95%; -9.9 to 6.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.2
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.274
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-4.7
	Confidence Interval	(2-Sided) 95%; -13.0 to 3.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.3
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Sitagliptin 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -10.6 to 6.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.3
	Estimation Comments

8. Secondary Outcome

Title	Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
Description	The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change.
Time Frame	Day 1 (Baseline) and Week 26

Outcome Measure Data

Analysis Population Description

Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Arm/Group Title	Placebo/Sitagliptin	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Measure Participants	171	357	336	336
Least Squares Mean (Standard Error) [Percent change]	3.7 (1.3)	10.4 (0.9)	12.1 (1.0)	5.0 (1.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	6.7
	Confidence Interval	(2-Sided) 95%; 3.6 to 9.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.6
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	8.5
	Confidence Interval	(2-Sided) 95%; 5.4 to 11.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.6
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Sitagliptin 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -1.7 to 4.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.6
	Estimation Comments

9. Secondary Outcome

Title	Change in HbA1c From Baseline to Week 52
Description	The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change.
Time Frame	Day 1 (Baseline) and Week 52

Outcome Measure Data

Analysis Population Description

Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Arm/Group Title	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Measure Participants	365	360	354
Least Squares Mean (Standard Error) [Percent]	-0.73 (0.047)	-0.88 (0.047)	-0.73 (0.047)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assuming a discontinuation rate of 35% at Week 52, with a 2:2:2:1 treatment assignment ratio for canagliflozin 100 mg, canagliflozin 300 mg, sitagliptin 100 mg, or placebo, it was estimated that 360 subjects would need to be randomly assigned to each of the 3 active treatment groups and approximately 180 subjects to the placebo group to demonstrate non-inferiority with a non-inferiority margin of 0.3%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -0.119 to 0.122
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.061
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Canagliflozin 100 mg, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Assuming a discontinuation rate of 35% at Week 52, with a 2:2:2:1 treatment assignment ratio for canagliflozin 100 mg, canagliflozin 300 mg, sitagliptin 100 mg, or placebo, it was estimated that 360 subjects would need to be randomly assigned to each of the 3 active treatment groups and approximately 180 subjects to the placebo group to demonstrate non-inferiority with a non-inferiority margin of 0.3%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.273 to -0.031
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.062
	Estimation Comments

10. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52
Description	The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change.
Time Frame	Day 1 (Baseline) and Week 52

Outcome Measure Data

Analysis Population Description

Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Arm/Group Title	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Measure Participants	365	360	354
Least Squares Mean (Standard Error) [mg/dL]	-26.2 (1.814)	-35.2 (1.833)	-17.7 (1.848)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-8.55
	Confidence Interval	(2-Sided) 95%; -13.25 to -3.857
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.394
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Canagliflozin 100 mg, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-17.5
	Confidence Interval	(2-Sided) 95%; -22.24 to -12.81
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.404
	Estimation Comments

11. Secondary Outcome

Title	Percent Change in Body Weight From Baseline to Week 52
Description	The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change.
Time Frame	Day 1 (Baseline) and Week 52

Outcome Measure Data

Analysis Population Description

Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Arm/Group Title	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Measure Participants	365	360	355
Least Squares Mean (Standard Error) [Percent change]	-3.8 (0.2)	-4.2 (0.2)	-1.3 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -3.0 to -1.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Canagliflozin 100 mg, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -3.4 to -2.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

12. Secondary Outcome

Title	Change in Systolic Blood Pressure (SBP) From Baseline to Week 52
Description	The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change.
Time Frame	Day 1 (Baseline) and Week 52

Outcome Measure Data

Analysis Population Description

Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Arm/Group Title	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Measure Participants	365	360	355
Least Squares Mean (Standard Error) [mmHg]	-3.53 (0.615)	-4.65 (0.618)	-0.66 (0.625)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-2.87
	Confidence Interval	(2-Sided) 95%; -4.464 to -1.276
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.812
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Canagliflozin 100 mg, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-3.99
	Confidence Interval	(2-Sided) 95%; -5.589 to -2.389
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.815
	Estimation Comments

13. Secondary Outcome

Title	Percent Change in Triglycerides From Baseline to Week 52
Description	The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change.
Time Frame	Day 1 (Baseline) and Week 52

Outcome Measure Data

Analysis Population Description

Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Arm/Group Title	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Measure Participants	359	343	339
Least Squares Mean (Standard Error) [Percent change]	1.9 (2.4)	2.7 (2.4)	-0.4 (2.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.466
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	2.3
	Confidence Interval	(2-Sided) 95%; -3.9 to 8.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.2
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Canagliflozin 100 mg, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.323
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	3.2
	Confidence Interval	(2-Sided) 95%; -3.1 to 9.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.2
	Estimation Comments

14. Secondary Outcome

Title	Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52
Description	The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change.
Time Frame	Day 1 (Baseline) and Week 52

Outcome Measure Data

Analysis Population Description

Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

Arm/Group Title	Canagliflozin 100 mg	Canagliflozin 300 mg	Sitagliptin 100 mg
Arm/Group Description	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
Measure Participants	359	343	338
Least Squares Mean (Standard Error) [Percent change]	11.2 (1.0)	13.3 (1.1)	6.0 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Sitagliptin, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	5.2
	Confidence Interval	(2-Sided) 95%; 2.5 to 8.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Canagliflozin 100 mg, Canagliflozin 300 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	7.3
	Confidence Interval	(2-Sided) 95%; 4.5 to 10.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4
	Estimation Comments

Adverse Events

Time Frame	Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks.
Adverse Event Reporting Description	The total number of adverse events listed in the "Other (non-Serious) Adverse Event" 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.
Arm/Group Title	Placebo/Sitagliptin: Baseline to Week 26		Canagliflozin 100 mg: Baseline to Week 26		Canagliflozin 300 mg: Baseline to Week 26		Sitagliptin 100 mg: Baseline to Week 26		Placebo/Sitagliptin: Baseline to Week 52		Canagliflozin 100 mg: Baseline to Week 52		Canagliflozin 300 mg: Baseline to Week 52		Sitagliptin 100mg: Baseline to Week 52
Arm/Group Description	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release. Data are presented for Baseline to Week 26.		Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release. Data are presented for Baseline to Week 26.		Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release. Data are presented for Baseline to Week 26.		Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release. Data are presented for Baseline to Week 26.		Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release. Data are presented for Baseline to Week 52.		Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release. Data are presented for Baseline to Week 52.		Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release. Data are presented for Baseline to Week 52.		Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release. Data are presented for Baseline to Week 52.
All Cause Mortality
	Placebo/Sitagliptin: Baseline to Week 26		Canagliflozin 100 mg: Baseline to Week 26		Canagliflozin 300 mg: Baseline to Week 26		Sitagliptin 100 mg: Baseline to Week 26		Placebo/Sitagliptin: Baseline to Week 52		Canagliflozin 100 mg: Baseline to Week 52		Canagliflozin 300 mg: Baseline to Week 52		Sitagliptin 100mg: Baseline to Week 52
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo/Sitagliptin: Baseline to Week 26		Canagliflozin 100 mg: Baseline to Week 26		Canagliflozin 300 mg: Baseline to Week 26		Sitagliptin 100 mg: Baseline to Week 26		Placebo/Sitagliptin: Baseline to Week 52		Canagliflozin 100 mg: Baseline to Week 52		Canagliflozin 300 mg: Baseline to Week 52		Sitagliptin 100mg: Baseline to Week 52
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/183 (2.2%)		12/368 (3.3%)		10/367 (2.7%)		8/366 (2.2%)		7/183 (3.8%)		15/368 (4.1%)		12/367 (3.3%)		18/366 (4.9%)
Cardiac disorders
Acute coronary syndrome	1/183 (0.5%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		1/183 (0.5%)		0/368 (0%)		0/367 (0%)		0/366 (0%)
Angina unstable	0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Coronary artery disease	0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		1/366 (0.3%)
Stress cardiomyopathy	0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Supraventricular tachycardia	0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)
Acute myocardial infarction	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Atrial fibrillation	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)
Cardiac arrest	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Cardiomyopathy	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)
Myocardial infarction	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Ear and labyrinth disorders
Vertigo	0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)
Eye disorders
Cataract nuclear	0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)
Gastrointestinal disorders
Abdominal pain	0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)
Constipation	0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Inguinal hernia	1/183 (0.5%)		1/368 (0.3%)		1/367 (0.3%)		0/366 (0%)		1/183 (0.5%)		1/368 (0.3%)		1/367 (0.3%)		0/366 (0%)
Umbilical hernia	0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)
Abdominal hernia	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Diverticulum	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
General disorders
Hernia obstructive	0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)
Hepatobiliary disorders
Cholangitis	0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)
Cholecystitis acute	0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Cholecystitis	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)
Infections and infestations
Cellulitis	0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)		1/183 (0.5%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Gastroenteritis	0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		1/366 (0.3%)
Pneumonia	0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)
Pyothorax	0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)
Sepsis	0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)		1/183 (0.5%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)
Subcutaneous abscess	0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)
Urinary tract infection	0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		1/367 (0.3%)		0/366 (0%)
Dengue fever	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Infectious pleural effusion	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)
Lobar pneumonia	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Septic shock	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Injury, poisoning and procedural complications
Burns second degree	0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)
Cervical vertebral fracture	0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)
Incisional hernia	1/183 (0.5%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		1/183 (0.5%)		0/368 (0%)		0/367 (0%)		0/366 (0%)
Incisional hernia, obstructive	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Multiple drug overdose	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Thermal burn	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Musculoskeletal and connective tissue disorders
Plantar fasciitis	0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Spinal column stenosis	0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Intervertebral disc protrusion	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer in situ	0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Gastric cancer	1/183 (0.5%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		1/183 (0.5%)		0/368 (0%)		0/367 (0%)		0/366 (0%)
Malignant mesenchymoma	0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Meningioma	0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Bronchial carcinoma	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Colorectal cancer	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Large cell lung cancer stage III	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Prostate cancer	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Nervous system disorders
Brain oedema	0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Coma	0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Ischaemic stroke	0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Transient ischaemic attack	0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		1/368 (0.3%)		0/367 (0%)		0/366 (0%)
Cerebrovascular accident	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Trigeminal neuralgia	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		1/183 (0.5%)		0/368 (0%)		0/367 (0%)		0/366 (0%)
Pregnancy, puerperium and perinatal conditions
High risk pregnancy	0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Renal and urinary disorders
Renal failure acute	0/183 (0%)		0/368 (0%)		0/367 (0%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Respiratory failure	0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)		0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Vascular disorders
Arterial thrombosis	0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)		0/183 (0%)		0/368 (0%)		1/367 (0.3%)		0/366 (0%)
Hypertensive crisis	0/183 (0%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)		1/183 (0.5%)		0/368 (0%)		0/367 (0%)		1/366 (0.3%)
Other (Not Including Serious) Adverse Events
	Placebo/Sitagliptin: Baseline to Week 26		Canagliflozin 100 mg: Baseline to Week 26		Canagliflozin 300 mg: Baseline to Week 26		Sitagliptin 100 mg: Baseline to Week 26		Placebo/Sitagliptin: Baseline to Week 52		Canagliflozin 100 mg: Baseline to Week 52		Canagliflozin 300 mg: Baseline to Week 52		Sitagliptin 100mg: Baseline to Week 52
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/183 (16.9%)		55/368 (14.9%)		45/367 (12.3%)		42/366 (11.5%)		55/183 (30.1%)		108/368 (29.3%)		101/367 (27.5%)		109/366 (29.8%)
Gastrointestinal disorders
Diarrhoea	12/183 (6.6%)		12/368 (3.3%)		18/367 (4.9%)		16/366 (4.4%)		13/183 (7.1%)		15/368 (4.1%)		23/367 (6.3%)		23/366 (6.3%)
Infections and infestations
Nasopharyngitis	13/183 (7.1%)		15/368 (4.1%)		10/367 (2.7%)		14/366 (3.8%)		13/183 (7.1%)		18/368 (4.9%)		16/367 (4.4%)		22/366 (6%)
Upper respiratory tract infection	6/183 (3.3%)		5/368 (1.4%)		18/367 (4.9%)		18/366 (4.9%)		10/183 (5.5%)		12/368 (3.3%)		23/367 (6.3%)		22/366 (6%)
Urinary tract infection	4/183 (2.2%)		18/368 (4.9%)		13/367 (3.5%)		12/366 (3.3%)		12/183 (6.6%)		27/368 (7.3%)		17/367 (4.6%)		22/366 (6%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/183 (4.9%)		7/368 (1.9%)		4/367 (1.1%)		11/366 (3%)		11/183 (6%)		10/368 (2.7%)		9/367 (2.5%)		17/366 (4.6%)
Back pain	6/183 (3.3%)		8/368 (2.2%)		12/367 (3.3%)		4/366 (1.1%)		10/183 (5.5%)		13/368 (3.5%)		15/367 (4.1%)		10/366 (2.7%)
Nervous system disorders
Headache	12/183 (6.6%)		12/368 (3.3%)		10/367 (2.7%)		16/366 (4.4%)		13/183 (7.1%)		19/368 (5.2%)		13/367 (3.5%)		19/366 (5.2%)
Renal and urinary disorders
Pollakiuria	1/183 (0.5%)		21/368 (5.7%)		10/367 (2.7%)		2/366 (0.5%)		1/183 (0.5%)		21/368 (5.7%)		11/367 (3%)		2/366 (0.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring 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 in writing, such publication will be withheld for up to an additional 60 days.