An Efficacy, Safety, and Tolerability Study of Canagliflozin (JNJ-28431754) in Patients With Type 2 Diabetes

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00642278
• Collaborator: (none)
• Enrollment: 451
• Locations: 85
• Arms: 7
• Duration (Months): 9
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effectiveness, safety, and tolerability of JNJ-28431754 compared with placebo in patients with type 2 diabetes.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type II; Diabetes Mellitus, Non Insulin Dependent	Drug: Canagliflozin (JNJ-28431754); Drug: Sitagliptin; Drug: Placebo	Phase 2

Detailed Description

Type 2 diabetes mellitus is a metabolic disorder that is characterized by decreased secretion of insulin by the pancreas and resistance to the action of insulin in various tissues (muscle, liver, and adipose), which results in impaired glucose uptake. Chronic hyperglycemia leads to progressive impairment of insulin secretion and to insulin resistance of peripheral tissues in diabetes (so-called glucose toxicity), which further worsens control of blood glucose. In addition, chronic hyperglycemia is a major risk factor for complications, including heart disease, retinopathy, nephropathy, and neuropathy. Although numerous treatments have been developed for the treatment of diabetes and individual agents may be highly effective for some patients, it is still difficult to maintain optimal glycemic control in most patients with diabetes. This is a randomized, double-blind, placebo-controlled, parallel group, multicenter, dose-ranging study to determine the efficacy, safety and tolerability of JNJ-28431754 taken orally over 12 weeks, compared with placebo, in the treatment of Type 2 diabetes mellitus. The primary clinical hypothesis is that JNJ-28431754 is superior to placebo as measured by the change in hemoglobin A1c from baseline through Week 12 in the treatment of type 2 diabetes mellitus. Subject safety will be monitored throughout the study using spontaneous adverse event reporting, clinical laboratory tests (hematology, serum chemistry, urinalysis); severe and serious hypoglycemic episodes, assessment of urinary albumin excretion and markers of proximal renal tubular function; pregnancy tests; electrocardiograms (ECGs); vital sign measurements; physical examinations, assessment of calcium and phosphate homeostasis, bone formation and resorption markers, and hormones regulating calcium and phosphorus homeostasis; and vaginal and urine sample collection for fungal and bacterial culture in subjects with symptoms consistent with vulvovaginal candidiasis (VVC) or urinary tract infection (UTI).

Study Design

• Study Type: Interventional
• Actual Enrollment: 451 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Double-Dummy, Parallel Group, Multicenter, Dose-Ranging Study in Subjects With Type 2 Diabetes Mellitus to Evaluate the Efficacy, Safety, and Tolerability of Orally Administered SGLT2 Inhibitor JNJ-28431754 With Sitagliptin as a Reference Arm
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Canagliflozin 50 mg daily Each patient will receive 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Drug: Canagliflozin (JNJ-28431754); One 50 mg, 100 mg, 200 mg, or 300 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks or one 300 mg over-encapsulated tablet orally twice daily for 12 weeks.; Other Names: JNJ-28431754 ; Drug: Placebo; One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.
Experimental: Canagliflozin 100 mg daily Each patient will receive 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Drug: Canagliflozin (JNJ-28431754); One 50 mg, 100 mg, 200 mg, or 300 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks or one 300 mg over-encapsulated tablet orally twice daily for 12 weeks.; Other Names: JNJ-28431754 ; Drug: Placebo; One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.
Experimental: Canagliflozin 200 mg daily Each patient will receive 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Drug: Canagliflozin (JNJ-28431754); One 50 mg, 100 mg, 200 mg, or 300 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks or one 300 mg over-encapsulated tablet orally twice daily for 12 weeks.; Other Names: JNJ-28431754 ; Drug: Placebo; One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.
Experimental: Canagliflozin 300 mg daily Each patient will receive 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo capsule once daily (in the evening).	Drug: Canagliflozin (JNJ-28431754); One 50 mg, 100 mg, 200 mg, or 300 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks or one 300 mg over-encapsulated tablet orally twice daily for 12 weeks.; Other Names: JNJ-28431754 ; Drug: Placebo; One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.
Experimental: Canagliflozin 300 mg twice daily Each patient will receive 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.	Drug: Canagliflozin (JNJ-28431754); One 50 mg, 100 mg, 200 mg, or 300 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks or one 300 mg over-encapsulated tablet orally twice daily for 12 weeks.; Other Names: JNJ-28431754
Active Comparator: Sitagliptin 100 mg daily Each patient will receive 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Drug: Sitagliptin; One 100 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks.; Drug: Placebo; One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.
Placebo Comparator: Placebo Each patient will receive matching placebo twice daily for 12 weeks.	Drug: Placebo; One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c From Baseline to Week 12 [Day 1 (Baseline) and Week 12]

   The table below shows the mean change in HbA1c from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.

Secondary Outcome Measures

1. Change in Fasting Plasma Glucose (FPG) From Baseline to Week 12 [Day 1 (Baseline) and Week 12]

   The table below shows the mean change in FPG from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.

2. Percentage of Patients With Symptoms of Hypoglycemia [Up to Week 12]

   The table below shows the percentage of patients who experienced symptomatic hypoglycemic events between Baseline and Week 12.

3. Change in Overnight Urine Glucose/Creatinine Ratio From Baseline to Week 12 [Day 1 (Baseline) and Week 12]

   The table below shows the mean change in overnight urine glucose/creatinine ratio from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.

4. Absolute Change in Body Weight From Baseline to Week 12 [Day 1 (Baseline) and Week 12]

   The table below shows the mean absolute change in body weight from Baseline to Week 12 for each treatment group.

5. Percent Change in Body Weight From Baseline to Week 12 [Day 1 (Baseline) and Week 12]

   The table below shows the mean percent change in body weight from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have a diagnosis of type 2 diabetes mellitus

• Hemoglobin A1c levels >=7% and <=10.5%

• taking a stable daily dose of metformin

• Body mass index (BMI) 25 to 45 kg/m2 except those of Asian descent who must have a BMI of 24 to 45 kg/m2

• Stable body weight

• Serum creatinine <=1.5 mg/dL (132.6 umol/L) for men and <=1.4 mg/dL (123.76 umol/L) for women

Exclusion Criteria:

• Patients must not have prior exposure or known contraindication or suspected hypersensitivity to canagliflozin (JNJ-28431754)

• Known contraindication or suspected hypersensitivity to sitagliptin or metformin

• A history of diabetic ketoacidosis or type 1 diabetes mellitus

• History of pancreas or beta-cell transplantation

• History of active proliferative diabetic retinopathy

• History of hereditary glucose-galactose malabsorption or primary renal glucosuria

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Mesa	Arizona	United States
3		Tucson	Arizona	United States
4		Encinitas	California	United States
5		Lincoln	California	United States
6		Los Angeles	California	United States
7		Merced	California	United States
8		Roseville	California	United States
9		Denver	Colorado	United States
10		Golden	Colorado	United States
11		Hollywood	Florida	United States
12		Jacksonville	Florida	United States
13		Boise	Idaho	United States
14		Nampa	Idaho	United States
15		Topeka	Kansas	United States
16		Haverhill	Massachusetts	United States
17		Cherry Hill	New Jersey	United States
18		Albuquerque	New Mexico	United States
19		New Hyde Park	New York	United States
20		Salisbury	North Carolina	United States
21		Oklahoma City	Oklahoma	United States
22		Tulsa	Oklahoma	United States
23		Portland	Oregon	United States
24		Greer	South Carolina	United States
25		Dallas	Texas	United States
26		Houston	Texas	United States
27		New Braunfels	Texas	United States
28		Odessa	Texas	United States
29		San Antonio	Texas	United States
30		Milwaukee	Wisconsin	United States
31		Buenos Aires		Argentina
32		Bueos Aires		Argentina
33		Pleven		Bulgaria
34		Sofia N/A		Bulgaria
35		Sofia		Bulgaria
36		Chilliwack	British Columbia	Canada
37		Coquitlam	British Columbia	Canada
38		Brampton	Ontario	Canada
39		Sarnia	Ontario	Canada
40		Toronto	Ontario	Canada
41		Pointe-Claire	Quebec	Canada
42		St Romuald	Quebec	Canada
43		Saskatoon	Saskatchewan	Canada
44		Olomouc 9		Czech Republic
45		Pisek 1		Czech Republic
46		Praha 28		Czech Republic
47		Praha 5		Czech Republic
48		Praha		Czech Republic
49		Bangalore		India
50		Hyderabad		India
51		Nagpur		India
52		Pune		India
53		Kota Bharu		Malaysia
54		Kuala Lumpur N/A		Malaysia
55		Kuala Lumpur		Malaysia
56		Ciudad De Mexico		Mexico
57		Mexico		Mexico
58		Monterrey		Mexico
59		Zapopan		Mexico
60		Bydgoszcz		Poland
61		Gdansk		Poland
62		Kutno 001		Poland
63		Lodz		Poland
64		Lublin N/A		Poland
65		Torun		Poland
66		Warszawa		Poland
67		Wroclaw		Poland
68		Ponce Pr		Puerto Rico
69		San Juan		Puerto Rico
70		Baia Mare		Romania
71		Brasov		Romania
72		Bucharest		Romania
73		Cluj		Romania
74		Galati		Romania
75		Ploiesti		Romania
76		Moscow N/A		Russian Federation
77		Moscow		Russian Federation
78		Saint Petersburg		Russian Federation
79		Samara		Russian Federation
80		St Petersburg N/A		Russian Federation
81		St-Petersburg		Russian Federation
82		Belfast		United Kingdom
83		Bolton		United Kingdom
84		Exeter		United Kingdom
85		Lincoln		United Kingdom

Sponsors and Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• ClinicalTrials.gov Identifier: NCT00642278
• Other Study ID Numbers: CR014587; 28431754DIA2001
• First Posted: Mar 25, 2008
• Last Update Posted: Jul 19, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: Type 2 diabetes mellitus; Metformin; Hemoglobin A1c
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Sitagliptin Phosphate; Canagliflozin

Study Results

Participant Flow

Recruitment Details	This study evaluated the efficacy and safety of canagliflozin (JNJ-28431754) in patients with type 2 diabetes mellitus with sitagliptin as a reference arm. The study was conducted between 27 March 2008 and 28 January 2009 and recruited patients from 85 study centers located in 13 countries worldwide.
Pre-assignment Detail	A total of 451 patients were randomly allocated to the 7 treatment arms in the study and comprised the intent-to-treat analysis set which was used for the efficacy analyses. All 451 patients received at least 1 dose of study drug and were included in the safety analysis set.

Arm/Group Title	Placebo	Canagliflozin 50 mg Daily	Canagliflozin 100 mg Daily	Canagliflozin 200 mg Daily	Canagliflozin 300 mg Daily	Canagliflozin 300 mg Twice Daily	Sitagliptin 100 mg Daily
Arm/Group Description	Each patient received matching placebo twice daily for 12 weeks.	Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.	Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Period Title: Overall Study
STARTED	65	64	64	65	64	64	65
COMPLETED	55	59	59	56	56	57	60
NOT COMPLETED	10	5	5	9	8	7	5

Baseline Characteristics

Arm/Group Title	Placebo	Canagliflozin 50 mg Daily	Canagliflozin 100 mg Daily	Canagliflozin 200 mg Daily	Canagliflozin 300 mg Daily	Canagliflozin 300 mg Twice Daily	Sitagliptin 100 mg Daily	Total
Arm/Group Description	Each patient received matching placebo twice daily for 12 weeks.	Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.	Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Total of all reporting groups
Overall Participants	65	64	64	65	64	64	65	451
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	63 96.9%	61 95.3%	63 98.4%	61 93.8%	63 98.4%	62 96.9%	65 100%	438 97.1%
>=65 years	2 3.1%	3 4.7%	1 1.6%	4 6.2%	1 1.6%	2 3.1%	0 0%	13 2.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.3 (7.82)	53.3 (8.48)	51.7 (7.95)	52.9 (9.56)	52.3 (6.88)	55.2 (7.14)	51.7 (8.09)	52.9 (8.06)
Sex: Female, Male (Count of Participants)
Female	34 52.3%	30 46.9%	28 43.8%	32 49.2%	28 43.8%	36 56.3%	27 41.5%	215 47.7%
Male	31 47.7%	34 53.1%	36 56.3%	33 50.8%	36 56.3%	28 43.8%	38 58.5%	236 52.3%
Region Enroll (participants) [Number]
ARGENTINA	1 1.5%	1 1.6%	3 4.7%	1 1.5%	2 3.1%	0 0%	2 3.1%	10 2.2%
BULGARIA	1 1.5%	1 1.6%	1 1.6%	0 0%	3 4.7%	3 4.7%	1 1.5%	10 2.2%
CANADA	11 16.9%	6 9.4%	9 14.1%	8 12.3%	8 12.5%	4 6.3%	7 10.8%	53 11.8%
CZECH REPUBLIC	2 3.1%	3 4.7%	2 3.1%	6 9.2%	0 0%	2 3.1%	2 3.1%	17 3.8%
INDIA	4 6.2%	6 9.4%	3 4.7%	5 7.7%	2 3.1%	6 9.4%	4 6.2%	30 6.7%
MALAYSIA	3 4.6%	0 0%	6 9.4%	2 3.1%	4 6.3%	1 1.6%	3 4.6%	19 4.2%
MEXICO	4 6.2%	6 9.4%	9 14.1%	9 13.8%	6 9.4%	14 21.9%	2 3.1%	50 11.1%
POLAND	3 4.6%	5 7.8%	4 6.3%	7 10.8%	6 9.4%	5 7.8%	9 13.8%	39 8.6%
ROMANIA	9 13.8%	8 12.5%	4 6.3%	6 9.2%	6 9.4%	5 7.8%	8 12.3%	46 10.2%
RUSSIAN FEDERATION	5 7.7%	7 10.9%	5 7.8%	2 3.1%	6 9.4%	3 4.7%	4 6.2%	32 7.1%
UNITED KINGDOM	1 1.5%	0 0%	2 3.1%	1 1.5%	3 4.7%	1 1.6%	2 3.1%	10 2.2%
UNITED STATES	21 32.3%	21 32.8%	16 25%	18 27.7%	18 28.1%	20 31.3%	21 32.3%	135 29.9%

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c From Baseline to Week 12
Description	The table below shows the mean change in HbA1c from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.
Time Frame	Day 1 (Baseline) and Week 12

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when Week 12 values were missing. The table includes only patients with both baseline and post baseline values.

Arm/Group Title	Placebo	Canagliflozin 50 mg Daily	Canagliflozin 100 mg Daily	Canagliflozin 200 mg Daily	Canagliflozin 300 mg Daily	Canagliflozin 300 mg Twice Daily	Sitagliptin 100 mg Daily
Arm/Group Description	Each patient received matching placebo twice daily for 12 weeks.	Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.	Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Measure Participants	61	62	62	62	60	62	62
Mean (Standard Deviation) [Percent]	-0.22 (0.702)	-0.79 (0.749)	-0.76 (0.992)	-0.70 (0.720)	-0.92 (0.695)	-0.95 (0.704)	-0.74 (0.615)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 50 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Adjusted using Dunnett's procedure.
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-0.45
	Confidence Interval	(2-Sided) 95%; -0.747 to -0.148
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.116
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 100 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Adjusted using Dunnett's procedure.
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-0.51
	Confidence Interval	(2-Sided) 95%; -0.804 to -0.207
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.116
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 200 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Adjusted using Dunnett's procedure.
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-0.54
	Confidence Interval	(2-Sided) 95%; -0.841 to -0.244
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.116
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 300 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Adjusted using Dunnett's procedure.
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95%; -1.006 to -0.405
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.117
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 300 mg Twice Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Adjusted using Dunnett's procedure.
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-0.73
	Confidence Interval	(2-Sided) 95%; -1.029 to -0.432
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.116
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sitagliptin 100 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Adjusted using Dunnett's procedure.
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-0.56
	Confidence Interval	(2-Sided) 95%; -0.862 to -0.265
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.116
	Estimation Comments

2. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG) From Baseline to Week 12
Description	The table below shows the mean change in FPG from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.
Time Frame	Day 1 (Baseline) and Week 12

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when Week 12 values were missing. The table includes only patients with both baseline and post baseline values.

Arm/Group Title	Placebo	Canagliflozin 50 mg Daily	Canagliflozin 100 mg Daily	Canagliflozin 200 mg Daily	Canagliflozin 300 mg Daily	Canagliflozin 300 mg Twice Daily	Sitagliptin 100 mg Daily
Arm/Group Description	Each patient received matching placebo twice daily for 12 weeks.	Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.	Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Measure Participants	62	63	63	62	61	62	64
Mean (Standard Deviation) [mmol/L]	0.2 (1.58)	-0.9 (2.26)	-1.4 (1.70)	-1.5 (2.23)	-1.4 (1.87)	-1.3 (1.54)	-0.7 (1.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 50 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.39 to -0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 100 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -1.98 to -0.92
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 200 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -2.33 to -1.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 300 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -2.32 to -1.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 300 mg Twice Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -2.25 to -1.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sitagliptin 100 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -1.51 to -0.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Patients With Symptoms of Hypoglycemia
Description	The table below shows the percentage of patients who experienced symptomatic hypoglycemic events between Baseline and Week 12.
Time Frame	Up to Week 12

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomiy assigned to a treatment group.

Arm/Group Title	Placebo	Canagliflozin 50 mg Daily	Canagliflozin 100 mg Daily	Canagliflozin 200 mg Daily	Canagliflozin 300 mg Daily	Canagliflozin 300 mg Twice Daily	Sitagliptin 100 mg Daily
Arm/Group Description	Each patient received matching placebo twice daily for 12 weeks.	Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.	Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Measure Participants	65	64	64	65	64	64	65
Number [Percentage of patients]	2	0	2	6	0	3	5

4. Secondary Outcome

Title	Change in Overnight Urine Glucose/Creatinine Ratio From Baseline to Week 12
Description	The table below shows the mean change in overnight urine glucose/creatinine ratio from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.
Time Frame	Day 1 (Baseline) and Week 12

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when Week 12 values were missing. The table includes only patients with both baseline and post baseline values.

Arm/Group Title	Placebo	Canagliflozin 50 mg Daily	Canagliflozin 100 mg Daily	Canagliflozin 200 mg Daily	Canagliflozin 300 mg Daily	Canagliflozin 300 mg Twice Daily	Sitagliptin 100 mg Daily
Arm/Group Description	Each patient received matching placebo twice daily for 12 weeks.	Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.	Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Measure Participants	54	58	56	53	57	56	58
Mean (Standard Deviation) [mg/mg]	1.9 (12.34)	35.4 (28.98)	51.5 (28.83)	50.5 (24.38)	49.4 (38.41)	61.6 (37.85)	-1.9 (14.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 50 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Sqaures Mean Difference
	Estimated Value	36.1
	Confidence Interval	(2-Sided) 95%; 26.07 to 46.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.10
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 100 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Sqaures Mean Difference
	Estimated Value	49.3
	Confidence Interval	(2-Sided) 95%; 39.17 to 59.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.13
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 200 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Sqaures Mean Difference
	Estimated Value	48.2
	Confidence Interval	(2-Sided) 95%; 37.98 to 58.42
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.2
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 300 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	49.0
	Confidence Interval	(2-Sided) 95%; 38.91 to 59.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.11
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 300 mg Twice Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Sqaures Mean Difference
	Estimated Value	60.3
	Confidence Interval	(2-Sided) 95%; 50.17 to 70.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.13
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sitagliptin 100 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.513
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-3.3
	Confidence Interval	(2-Sided) 95%; -13.33 to 6.67
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.09
	Estimation Comments

5. Secondary Outcome

Title	Absolute Change in Body Weight From Baseline to Week 12
Description	The table below shows the mean absolute change in body weight from Baseline to Week 12 for each treatment group.
Time Frame	Day 1 (Baseline) and Week 12

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when Week 12 values were missing. The table includes only patients with both baseline and post baseline values.

Arm/Group Title	Placebo	Canagliflozin 50 mg Daily	Canagliflozin 100 mg Daily	Canagliflozin 200 mg Daily	Canagliflozin 300 mg Daily	Canagliflozin 300 mg Twice Daily	Sitagliptin 100 mg Daily
Arm/Group Description	Each patient received matching placebo twice daily for 12 weeks.	Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.	Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Measure Participants	62	63	64	63	62	62	64
Mean (Standard Deviation) [kg]	-0.78 (2.099)	-1.96 (2.334)	-2.25 (2.145)	-2.32 (2.842)	-2.88 (2.391)	-2.87 (2.344)	-0.43 (2.693)

6. Secondary Outcome

Title	Percent Change in Body Weight From Baseline to Week 12
Description	The table below shows the mean percent change in body weight from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.
Time Frame	Day 1 (Baseline) and Week 12

Outcome Measure Data

Analysis Population Description

This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when Week 12 values were missing. The table includes only patients with both baseline and post baseline values.

Arm/Group Title	Placebo	Canagliflozin 50 mg Daily	Canagliflozin 100 mg Daily	Canagliflozin 200 mg Daily	Canagliflozin 300 mg Daily	Canagliflozin 300 mg Twice Daily	Sitagliptin 100 mg Daily
Arm/Group Description	Each patient received matching placebo twice daily for 12 weeks.	Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).	Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.	Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Measure Participants	62	63	64	63	62	62	64
Mean (Standard Deviation) [Percent change]	-1.1 (2.4)	-2.3 (2.8)	-2.6 (2.3)	-2.7 (3.0)	-3.4 (2.8)	-3.4 (2.6)	-0.6 (3.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 50 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Sqaures Mean Difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.2 to -0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 100 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Sqaures Mean Difference
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -2.5 to -0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 200 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and mixed meal tolerance test.
Method of Estimation	Estimation Parameter	Least-Sqaures Mean Difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.6 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 300 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Sqaures Mean Difference
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -3.3 to -1.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Canagliflozin 300 mg Twice Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Sqaures Mean Difference
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -3.3 to -1.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sitagliptin 100 mg Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.371
	Comments
	Method	ANCOVA
	Comments	ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation	Estimation Parameter	Least-Sqaures Mean Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.5 to 1.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

Adverse Events

Time Frame	Adverse events were reported for the duration of the study; each patient participated in the study for approximately 12 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		Canagliflozin 50 mg Daily		Canagliflozin 100 mg Daily		Canagliflozin 200 mg Daily		Canagliflozin 300 mg Daily		Canagliflozin 300 mg Twice Daily		Sitagliptin 100 mg Daily
Arm/Group Description	Each patient received matching placebo twice daily for 12 weeks.		Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).		Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).		Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).		Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).		Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.		Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
All Cause Mortality
	Placebo		Canagliflozin 50 mg Daily		Canagliflozin 100 mg Daily		Canagliflozin 200 mg Daily		Canagliflozin 300 mg Daily		Canagliflozin 300 mg Twice Daily		Sitagliptin 100 mg Daily
	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)
Serious Adverse Events
	Placebo		Canagliflozin 50 mg Daily		Canagliflozin 100 mg Daily		Canagliflozin 200 mg Daily		Canagliflozin 300 mg Daily		Canagliflozin 300 mg Twice Daily		Sitagliptin 100 mg Daily
	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	1/65 (1.5%)		1/64 (1.6%)		1/64 (1.6%)		1/65 (1.5%)		1/64 (1.6%)		1/64 (1.6%)		0/65 (0%)
Cardiac disorders
Atrial fibrillation	0/65 (0%)		0/64 (0%)		0/64 (0%)		0/65 (0%)		1/64 (1.6%)		0/64 (0%)		0/65 (0%)
Cardiac failure congestive	0/65 (0%)		0/64 (0%)		0/64 (0%)		0/65 (0%)		1/64 (1.6%)		0/64 (0%)		0/65 (0%)
Infections and infestations
Gastroenteritis	0/65 (0%)		0/64 (0%)		0/64 (0%)		0/65 (0%)		0/64 (0%)		1/64 (1.6%)		0/65 (0%)
Otitis externa	0/65 (0%)		1/64 (1.6%)		0/64 (0%)		0/65 (0%)		0/64 (0%)		0/64 (0%)		0/65 (0%)
Pneumonia	1/65 (1.5%)		0/64 (0%)		0/64 (0%)		0/65 (0%)		0/64 (0%)		0/64 (0%)		0/65 (0%)
Investigations
Blood creatine phosphokinase increased	1/65 (1.5%)		0/64 (0%)		0/64 (0%)		0/65 (0%)		0/64 (0%)		0/64 (0%)		0/65 (0%)
Metabolism and nutrition disorders
Gestational diabetes	0/65 (0%)		0/64 (0%)		0/64 (0%)		1/65 (1.5%)		0/64 (0%)		0/64 (0%)		0/65 (0%)
Musculoskeletal and connective tissue disorders
Spondylolisthesis	0/65 (0%)		0/64 (0%)		1/64 (1.6%)		0/65 (0%)		0/64 (0%)		0/64 (0%)		0/65 (0%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/65 (1.5%)		0/64 (0%)		0/64 (0%)		0/65 (0%)		0/64 (0%)		0/64 (0%)		0/65 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Canagliflozin 50 mg Daily		Canagliflozin 100 mg Daily		Canagliflozin 200 mg Daily		Canagliflozin 300 mg Daily		Canagliflozin 300 mg Twice Daily		Sitagliptin 100 mg Daily
	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	9/65 (13.8%)		13/64 (20.3%)		10/64 (15.6%)		10/65 (15.4%)		10/64 (15.6%)		12/64 (18.8%)		7/65 (10.8%)
Gastrointestinal disorders
Abdominal pain upper	1/65 (1.5%)		0/64 (0%)		0/64 (0%)		0/65 (0%)		2/64 (3.1%)		4/64 (6.3%)		0/65 (0%)
Nausea	0/65 (0%)		3/64 (4.7%)		1/64 (1.6%)		1/65 (1.5%)		3/64 (4.7%)		5/64 (7.8%)		1/65 (1.5%)
Infections and infestations
Nasopharyngitis	2/65 (3.1%)		5/64 (7.8%)		0/64 (0%)		0/65 (0%)		1/64 (1.6%)		1/64 (1.6%)		3/65 (4.6%)
Urinary tract infection	4/65 (6.2%)		3/64 (4.7%)		2/64 (3.1%)		6/65 (9.2%)		2/64 (3.1%)		3/64 (4.7%)		1/65 (1.5%)
Vulvovaginal mycotic infection	0/65 (0%)		4/64 (6.3%)		2/64 (3.1%)		4/65 (6.2%)		1/64 (1.6%)		3/64 (4.7%)		1/65 (1.5%)
Nervous system disorders
Headache	2/65 (3.1%)		1/64 (1.6%)		5/64 (7.8%)		2/65 (3.1%)		3/64 (4.7%)		1/64 (1.6%)		1/65 (1.5%)

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.