A Safety and Efficacy Study of Canagliflozin in Older Patients (55 to 80 Years of Age) With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01106651
First received: April 1, 2010
Last updated: August 1, 2014
Last verified: August 2014
Results First Received: April 1, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Canagliflozin 100 mg
Drug: Canagliflozin 300 mg
Drug: Antihyperglycemic agent(s)
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study evaluated the efficacy and safety of canagliflozin in older patients with type 2 diabetes mellitus with inadequate control on their current diabetes treatment regimen. The study began on 07 June 2010 and ended on 23 May 2013. Patients were recruited from 90 study centers located in 17 countries worldwide.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
716 patients were randomly allocated to the 3 treatment arms. 714 patients received at least 1 dose of study drug and were included in the modified intent-to-treat (mITT) analysis set and safety analysis set. Participant flow is presented for Baseline to Week 104 (Overall Study).

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Participant Flow:   Overall Study
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
STARTED     237     241     236  
COMPLETED     158     184     178  
NOT COMPLETED     79     57     58  
Adverse Event                 17                 9                 23  
Lost to Follow-up                 8                 2                 6  
Physician Decision                 4                 3                 1  
Protocol Violation                 1                 2                 1  
Withdrawal by Subject                 14                 7                 4  
Noncompliance with study drug                 1                 0                 2  
Not specified                 34                 31                 21  
Death                 0                 3                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Total Total of all reporting groups

Baseline Measures
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg     Total  
Number of Participants  
[units: participants]
  237     241     236     714  
Age  
[units: participants]
       
<=18 years     0     0     0     0  
Between 18 and 65 years     151     141     149     441  
>=65 years     86     100     87     273  
Age  
[units: years]
Mean ± Standard Deviation
  63.2  ± 6.21     64.3  ± 6.46     63.4  ± 5.99     63.6  ± 6.24  
Gender  
[units: participants]
       
Female     94     117     107     318  
Male     143     124     129     396  
Region of Enrollment  
[units: participants]
       
AUSTRALIA     6     6     11     23  
CANADA     24     32     28     84  
COLOMBIA     18     15     20     53  
FRANCE     2     2     3     7  
GREECE     1     1     1     3  
HONG KONG     1     1     2     4  
INDIA     8     3     11     22  
NEW ZEALAND     16     10     11     37  
POLAND     11     12     14     37  
ROMANIA     8     10     7     25  
SOUTH AFRICA     9     12     10     31  
SPAIN     2     3     8     13  
SWEDEN     4     4     2     10  
SWITZERLAND     2     2     0     4  
UKRAINE     3     8     3     14  
UNITED KINGDOM     19     22     8     49  
UNITED STATES     103     98     97     298  



  Outcome Measures
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1.  Primary:   Change in HbA1c From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

Measure Type Primary
Measure Title Change in HbA1c From Baseline to Week 26
Measure 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 group minus placebo) in the LS mean change.
Time Frame Day 1 (Baseline) and Week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  232     239     229  
Change in HbA1c From Baseline to Week 26  
[units: Percent]
Least Squares Mean ± Standard Error
  -0.03  ± 0.063     -0.60  ± 0.063     -0.73  ± 0.064  


Statistical Analysis 1 for Change in HbA1c From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] -0.57
Standard Error of the mean ± 0.069
95% Confidence Interval ( -0.708 to -0.436 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
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[2] Other relevant method information, such as adjustments or degrees of freedom:
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[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[4] Other relevant estimation information:
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Statistical Analysis 2 for Change in HbA1c From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] -0.70
Standard Error of the mean ± 0.070
95% Confidence Interval ( -0.841 to -0.566 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[4] Other relevant estimation information:
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2.  Secondary:   Percentage of Patients With HbA1c <7% at Week 26   [ Time Frame: Week 26 ]

Measure Type Secondary
Measure Title Percentage of Patients With HbA1c <7% at Week 26
Measure 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 (ie, each canagliflozin group minus placebo) in the percentage.
Time Frame Week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  232     239     229  
Percentage of Patients With HbA1c <7% at Week 26  
[units: Percentage of patients]
  28.0     47.7     58.5  


Statistical Analysis 1 for Percentage of Patients With HbA1c <7% at Week 26
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] Regression, Logistic
P Value [3] <0.001
Odds Ratio (OR) [4] 2.96
95% Confidence Interval ( 1.93 to 4.56 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
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[2] Other relevant method information, such as adjustments or degrees of freedom:
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[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[4] Other relevant estimation information:
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Statistical Analysis 2 for Percentage of Patients With HbA1c <7% at Week 26
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] Regression, Logistic
P Value [3] <0.001
Odds Ratio (OR) [4] 4.48
95% Confidence Interval ( 2.89 to 6.95 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[4] Other relevant estimation information:
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3.  Secondary:   Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

Measure Type Secondary
Measure Title Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26
Measure 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 group minus placebo) in the LS mean change.
Time Frame Day 1 (Baseline) and Week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  231     239     229  
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26  
[units: mg/dL]
Least Squares Mean ± Standard Error
  7.39  ± 2.875     -18.1  ± 2.860     -20.3  ± 2.920  


Statistical Analysis 1 for Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] -25.5
Standard Error of the mean ± 3.147
95% Confidence Interval ( -31.68 to -19.32 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
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[2] Other relevant method information, such as adjustments or degrees of freedom:
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[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
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Statistical Analysis 2 for Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] -27.7
Standard Error of the mean ± 3.179
95% Confidence Interval ( -33.97 to -21.49 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
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[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[4] Other relevant estimation information:
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4.  Secondary:   Percent Change in Body Weight From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

Measure Type Secondary
Measure Title Percent Change in Body Weight From Baseline to Week 26
Measure 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 group minus placebo) in the LS mean change.
Time Frame Day 1 (Baseline) and Week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  234     240     229  
Percent Change in Body Weight From Baseline to Week 26  
[units: Percent change]
Least Squares Mean ± Standard Error
  -0.1  ± 0.3     -2.4  ± 0.3     -3.1  ± 0.3  


Statistical Analysis 1 for Percent Change in Body Weight From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] -2.3
Standard Error of the mean ± 0.3
95% Confidence Interval ( -2.8 to -1.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
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Statistical Analysis 2 for Percent Change in Body Weight From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] -3.0
Standard Error of the mean ± 0.3
95% Confidence Interval ( -3.5 to -2.4 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
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5.  Secondary:   Change in Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition   [ Time Frame: Day 1 (Baseline) and Week 26 ]

Measure Type Secondary
Measure Title Change in Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition
Measure Description The table below shows the least-squares (LS) mean change in total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific DXA analysis for body composition. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
Time Frame Day 1 (Baseline) and Week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  50     56     60  
Change in Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition  
[units: kg]
Least Squares Mean ± Standard Error
  -0.28  ± 0.336     -1.87  ± 0.332     -2.38  ± 0.323  


Statistical Analysis 1 for Change in Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] -1.59
Standard Error of the mean ± 0.379
95% Confidence Interval ( -2.339 to -0.842 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] -2.10
Standard Error of the mean ± 0.371
95% Confidence Interval ( -2.833 to -1.368 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
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6.  Secondary:   Change in Region Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition   [ Time Frame: Day 1 (Baseline) and Week 26 ]

Measure Type Secondary
Measure Title Change in Region Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition
Measure Description Region percent total fat = body fat as a percentage of (body fat + lean body mass + bone mass content). The table below shows the least-squares (LS) mean change in region percent total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific dual-energy X-ray absorptiometry (DXA) analysis for body composition. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
Time Frame Day 1 (Baseline) and Week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  50     56     60  
Change in Region Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition  
[units: Percent]
Least Squares Mean ± Standard Error
  0.00  ± 0.270     -1.03  ± 0.268     -1.18  ± 0.261  


Statistical Analysis 1 for Change in Region Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] -1.03
Standard Error of the mean ± 0.305
95% Confidence Interval ( -1.633 to -0.428 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Region percent total fat
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Region Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] -1.18
Standard Error of the mean ± 0.300
95% Confidence Interval ( -1.772 to -0.587 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Region percent total fat
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



7.  Secondary:   Change in Tissue Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition   [ Time Frame: Day 1 (Baseline) and Week 26 ]

Measure Type Secondary
Measure Title Change in Tissue Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition
Measure Description Tissue percent total fat = body fat as a percentage of body fat + lean body mass. The table below shows the least-squares (LS) mean change in tissue percent total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific DXA analysis for body composition . The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
Time Frame Day 1 (Baseline) and Week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  50     56     60  
Change in Tissue Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition  
[units: Percent]
Least Squares Mean ± Standard Error
  0.02  ± 0.280     -1.04  ± 0.278     -1.18  ± 0.270  


Statistical Analysis 1 for Change in Tissue Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] ANCOVA
P Value [3] 0.001
Least-Squares Mean Difference [4] -1.05
Standard Error of the mean ± 0.316
95% Confidence Interval ( -1.677 to -0.430 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Tissue Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] -1.20
Standard Error of the mean ± 0.311
95% Confidence Interval ( -1.812 to -0.584 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



8.  Secondary:   Change in Systolic Blood Pressure (SBP) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

Measure Type Secondary
Measure Title Change in Systolic Blood Pressure (SBP) From Baseline to Week 26
Measure 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 group minus placebo) in the LS mean change.
Time Frame Day 1 (Baseline) and Week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  234     240     229  
Change in Systolic Blood Pressure (SBP) From Baseline to Week 26  
[units: mmHg]
Least Squares Mean ± Standard Error
  1.10  ± 1.039     -3.52  ± 1.035     -6.79  ± 1.056  


Statistical Analysis 1 for Change in Systolic Blood Pressure (SBP) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] -4.63
Standard Error of the mean ± 1.134
95% Confidence Interval ( -6.854 to -2.401 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Systolic Blood Pressure (SBP) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] -7.89
Standard Error of the mean ± 1.147
95% Confidence Interval ( -10.14 to -5.641 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



9.  Secondary:   Percent Change in Triglycerides From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

Measure Type Secondary
Measure Title Percent Change in Triglycerides From Baseline to Week 26
Measure 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 group minus placebo) in the LS mean change.
Time Frame Day 1 (Baseline) and Week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  206     227     222  
Percent Change in Triglycerides From Baseline to Week 26  
[units: Percent change]
Least Squares Mean ± Standard Error
  7.7  ± 3.4     2.8  ± 3.3     8.4  ± 3.4  


Statistical Analysis 1 for Percent Change in Triglycerides From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] ANCOVA
P Value [3] 0.194
Least-Squares Mean Difference [4] -4.8
Standard Error of the mean ± 3.7
95% Confidence Interval ( -12.1 to 2.5 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percent Change in Triglycerides From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] ANCOVA
P Value [3] 0.846
Least-Squares Mean Difference [4] 0.7
Standard Error of the mean ± 3.7
95% Confidence Interval ( -6.6 to 8.1 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



10.  Secondary:   Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

Measure Type Secondary
Measure Title Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
Measure Description The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 or each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
Time Frame Day 1 (Baseline) and Week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  206     225     222  
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26  
[units: Percent change]
Least Squares Mean ± Standard Error
  1.5  ± 1.2     6.8  ± 1.2     6.2  ± 1.2  


Statistical Analysis 1 for Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] 5.3
Standard Error of the mean ± 1.4
95% Confidence Interval ( 2.6 to 7.9 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] ANCOVA
P Value [3] <0.001
Least-Squares Mean Difference [4] 4.7
Standard Error of the mean ± 1.4
95% Confidence Interval ( 2.0 to 7.4 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



11.  Secondary:   Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

Measure Type Secondary
Measure Title Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26
Measure Description The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in lumbar spine BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change.
Time Frame Day 1 (Baseline) and Week 26  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  185     206     192  
Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26  
[units: Percent change]
Least Squares Mean ± Standard Error
  0.5  ± 0.3     0.7  ± 0.3     0.2  ± 0.3  


Statistical Analysis 1 for Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] ANCOVA
Least-Squares Mean Difference [3] 0.2
Standard Error of the mean ± 0.3
95% Confidence Interval ( -0.4 to 0.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] ANCOVA
Least-Squares Mean Difference [3] -0.3
Standard Error of the mean ± 0.3
95% Confidence Interval ( -0.9 to 0.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



12.  Secondary:   Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

Measure Type Secondary
Measure Title Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26
Measure Description The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in distal forearm BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change.
Time Frame Day 1 (Baseline) and Week 26  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  187     208     187  
Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26  
[units: Percent change]
Least Squares Mean ± Standard Error
  -0.5  ± 0.3     -0.7  ± 0.3     -0.8  ± 0.3  


Statistical Analysis 1 for Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] ANCOVA
Least-Squares Mean Difference [3] -0.3
Standard Error of the mean ± 0.3
95% Confidence Interval ( -0.9 to 0.4 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] ANCOVA
Least-Squares Mean Difference [3] -0.4
Standard Error of the mean ± 0.3
95% Confidence Interval ( -1.0 to 0.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



13.  Secondary:   Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

Measure Type Secondary
Measure Title Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26
Measure Description The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in femoral neck BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change.
Time Frame Day 1 (Baseline) and Week 26  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  183     209     190  
Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26  
[units: Percent change]
Least Squares Mean ± Standard Error
  -1.0  ± 0.3     -0.7  ± 0.3     -0.6  ± 0.3  


Statistical Analysis 1 for Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] ANCOVA
Least-Squares Mean Difference [3] 0.3
Standard Error of the mean ± 0.3
95% Confidence Interval ( -0.3 to 1.0 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] ANCOVA
Least-Squares Mean Difference [3] 0.4
Standard Error of the mean ± 0.3
95% Confidence Interval ( -0.3 to 1.1 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



14.  Secondary:   Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26   [ Time Frame: Day 1 (Baseline) and Week 26 ]

Measure Type Secondary
Measure Title Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26
Measure Description The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in total hip BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change.
Time Frame Day 1 (Baseline) and Week 26  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Placebo Each patient received matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Measured Values
    Placebo     Canagliflozin 100 mg     Canagliflozin 300 mg  
Number of Participants Analyzed  
[units: participants]
  183     209     190  
Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26  
[units: Percent change]
Least Squares Mean ± Standard Error
  -0.5  ± 0.2     -0.9  ± 0.2     -1.0  ± 0.2  


Statistical Analysis 1 for Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 100 mg
Method [2] ANCOVA
Least-Squares Mean Difference [3] -0.4
Standard Error of the mean ± 0.2
95% Confidence Interval ( -0.8 to -0.0 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26
Groups [1] Placebo vs. Canagliflozin 300 mg
Method [2] ANCOVA
Least-Squares Mean Difference [3] -0.5
Standard Error of the mean ± 0.2
95% Confidence Interval ( -0.9 to -0.1 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Other relevant estimation information:
  No text entered.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


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