Diabetes Mellitus, Type 2
Conditions
Keywords
Type 2 diabetes mellitus, Canagliflozin, Placebo, Sitagliptin, Januvia, Metformin Immediate Release (IR), Hemoglobin A1c
Brief summary
The purpose of this study is to evaluate the efficacy and safety of canagliflozin compared with sitagliptin and placebo in patients with type 2 diabetes mellitus who are receiving treatment with metformin monotherapy (i.e., treatment with a single drug) and have inadequate glycemic (blood sugar) control.
Detailed description
Canagliflozin is a drug that is being tested to see if it may be useful in treating patients diagnosed with type 2 diabetes mellitus (T2DM). This is a randomized (study drug assigned by chance), double-blind (neither the patient nor the study doctor will know the identity of assigned study drug), placebo- and active-controlled, parallel-group, 4-arm (4 treatment groups) multicenter study to determine the efficacy, safety, and tolerability of canagliflozin (100 mg and 300 mg) compared to placebo (a capsule that looks like all the other treatments but has no real medicine) and an active-control (sitagliptin 100 mg, an antihyperglycemic agent) in patients with T2DM who are not achieving an adequate response from current antihyperglycemic therapy with metformin Immediate Release (IR) to control their diabetes. Approximately 1,260 patients with T2DM who are receiving treatment with metformin IR and have inadequate glycemic (blood sugar) will receive once-daily treatment with canagliflozin (100 mg or 300 mg), sitagliptin 100 mg, or placebo capsules for 26 weeks (Period I) followed by another 26-weeks where patients treated with canagliflozin (100 mg or 300 mg) or sitagliptin 100 mg will continue treatment for an additional 26 weeks and patients treated with placebo will be switched to active double-blind treatment with sitagliptin 100 mg capsules administered once-daily for 26 weeks (Period II). In addition, all patients will take protocol specified stable doses of metformin IR along with assigned study drug for the duration of the study. Patients will participate in the study for approximately 59 to 71 weeks. During the study, if a patient's fasting blood sugar remains high despite treatment with study drug, metformin IR, and reinforcement with diet and exercise, the patient will receive treatment with glimepiride (rescue therapy) consistent with local prescribing information. During treatment, patients will be monitored for safety by review of adverse events, results from laboratory tests, 12-lead electrocardiograms (ECGs), vital sign measurements, body weight, physical examinations, and self-monitored blood glucose (SMGB) measurements. The primary outcome measure in the study is to assess the effect of canagliflozin relative to placebo on hemoglobin A1c (HbA1c) after 26 weeks of treatment. Study drug will be taken orally (by mouth) once daily before the first meal each day unless otherwise specified. Patients will take single-blind placebo for 2 weeks before randomization. After randomization, patients in the study will take double-blind canagliflozin (100 mg or 300 mg) or sitagliptin 100 mg for 52 weeks OR placebo for 26 weeks switched to double-blind treatment with sitaliptin 100 mg for 26 weeks.
Interventions
DRUGPlacebo
One matching placebo capsule orally (by mouth) once daily for 26 weeks with protocol-specified doses of metformin immediate release.
DRUGCanagliflozin
One 100 mg or 300 mg over-encapsulated tablet orally once daily for 52 weeks with protocol-specified doses of metformin immediate release.
DRUGSitagliptin
One 100 mg over-encapsulated tablet orally once daily for 52 weeks (sitagliptin 100 mg arm) or once daily beginning at Week 26 until Week 52 (placebo/sitagliptin arm). Sitagliptin will be given with protocol-specified doses of metformin immediate release.
DRUGMetformin immediate release
The patient's stable dose of metformin immediate release background therapy should be continued throughout the study.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* All patients must have a diagnosis of T2DM and be currently treated with metformin IR * Patients in the study must have a HbA1c between \>=7 and \<=10.5% * Patients must have a fasting plasma glucose (FPG) \<270 mg/dL (15 mmol/L)
Exclusion criteria
* History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, diabetes secondary to pancreatitis or pancreatectomy, or a severe hypoglycemic episode within 6 months before screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline to Week 26 | Day 1 (Baseline) and Week 26 | The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 | Day 1 (Baseline) and Week 26 | The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change. |
| Change in 2-hour Post-prandial Glucose From Baseline to Week 26 | Day 1 (Baseline) and Week 26 | The table below shows the least-squares (LS) mean change in 2-hour post-prandial glucose from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change. |
| Percent Change in Body Weight From Baseline to Week 26 | Day 1 (Baseline) and Week 26 | The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change. |
| Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 | Day 1 (Baseline) and Week 26 | The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change. |
| Percent Change in Triglycerides From Baseline to Week 26 | Day 1 (Baseline) and Week 26 | The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change. |
| Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 | Day 1 (Baseline) and Week 26 | The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change. |
| Percentage of Patients With HbA1c <7% at Week 26 | Week 26 | The table below shows the percentage of patients with HbA1c \<7% at Week 26 in each treatment group. The statistical analyses show the treatment differences between each canagliflozin or sitagliptin group and placebo. |
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52 | Day 1 (Baseline) and Week 52 | The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change. |
| Percent Change in Body Weight From Baseline to Week 52 | Day 1 (Baseline) and Week 52 | The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change. |
| Change in Systolic Blood Pressure (SBP) From Baseline to Week 52 | Day 1 (Baseline) and Week 52 | The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change. |
| Percent Change in Triglycerides From Baseline to Week 52 | Day 1 (Baseline) and Week 52 | The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change. |
| Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 | Day 1 (Baseline) and Week 52 | The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change. |
| Change in HbA1c From Baseline to Week 52 | Day 1 (Baseline) and Week 52 | The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change. |
Countries
Argentina, Bulgaria, Colombia, Czechia, Estonia, Greece, India, Latvia, Malaysia, Mexico, Peru, Poland, Portugal, Puerto Rico, Russia, Singapore, Slovakia, Sweden, Thailand, Turkey (Türkiye), Ukraine, United States
Participant flow
Recruitment details
This study evaluated the efficacy and safety of canagliflozin compared with sitagliptin and placebo in patients with type 2 diabetes mellitus with inadequate control despite treatment with metformin. The study was conducted between 07 April 2010 and 17 August 2012 and recruited patients from 169 study centers in 22 countries worldwide.
Pre-assignment details
1,284 patients were randomly allocated to the 4 treatment arms. All patients received at least 1 dose of study drug and were included in the modified intent-to-treat (mITT) analysis set (used for the Week 26 and week 52 efficacy analyses). All 1,284 patients were included in the Week 26 and Week 52 safety analysis sets.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Sitagliptin Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release. | 183 |
| Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release. | 368 |
| Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release. | 367 |
| Sitagliptin 100 mg Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release. | 366 |
| Total | 1,284 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Core Period: Baseline to Week 26 | Adverse Event | 7 | 18 | 6 | 8 |
| Core Period: Baseline to Week 26 | Creatinine or eGFR withdrawal criteria | 1 | 2 | 2 | 3 |
| Core Period: Baseline to Week 26 | Death | 0 | 0 | 1 | 0 |
| Core Period: Baseline to Week 26 | Lack of Efficacy | 1 | 0 | 0 | 0 |
| Core Period: Baseline to Week 26 | Lost to Follow-up | 3 | 1 | 6 | 3 |
| Core Period: Baseline to Week 26 | Noncompliance with study drug | 1 | 3 | 0 | 0 |
| Core Period: Baseline to Week 26 | Other | 8 | 14 | 8 | 23 |
| Core Period: Baseline to Week 26 | Physician Decision | 2 | 1 | 3 | 1 |
| Core Period: Baseline to Week 26 | Pregnancy | 0 | 1 | 0 | 0 |
| Core Period: Baseline to Week 26 | Product quality complaint | 0 | 1 | 1 | 0 |
| Core Period: Baseline to Week 26 | Protocol Violation | 0 | 1 | 0 | 3 |
| Core Period: Baseline to Week 26 | Study terminated by sponsor | 0 | 1 | 2 | 0 |
| Core Period: Baseline to Week 26 | Withdrawal by Subject | 5 | 3 | 15 | 6 |
| Extension Period: Week 26 to Week 52 | Adverse Event | 1 | 1 | 5 | 9 |
| Extension Period: Week 26 to Week 52 | Creatinine or eGFR withdrawal criteria | 2 | 4 | 3 | 2 |
| Extension Period: Week 26 to Week 52 | Death | 0 | 0 | 0 | 1 |
| Extension Period: Week 26 to Week 52 | Lack of Efficacy | 2 | 0 | 0 | 4 |
| Extension Period: Week 26 to Week 52 | Lost to Follow-up | 0 | 2 | 2 | 2 |
| Extension Period: Week 26 to Week 52 | Other | 6 | 5 | 8 | 5 |
| Extension Period: Week 26 to Week 52 | Physician Decision | 2 | 3 | 2 | 3 |
| Extension Period: Week 26 to Week 52 | Protocol Violation | 1 | 0 | 0 | 0 |
| Extension Period: Week 26 to Week 52 | Unable to take rescue therapy | 0 | 0 | 0 | 1 |
| Extension Period: Week 26 to Week 52 | Withdrawal by Subject | 1 | 3 | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo/Sitagliptin | Canagliflozin 100 mg | Canagliflozin 300 mg | Sitagliptin 100 mg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 37 Participants | 54 Participants | 58 Participants | 57 Participants | 206 Participants |
| Age, Categorical Between 18 and 65 years | 146 Participants | 314 Participants | 309 Participants | 309 Participants | 1078 Participants |
| Age Continuous | 55.3 years STANDARD_DEVIATION 9.76 | 55.5 years STANDARD_DEVIATION 9.38 | 55.3 years STANDARD_DEVIATION 9.19 | 55.5 years STANDARD_DEVIATION 9.55 | 55.4 years STANDARD_DEVIATION 9.42 |
| Region Enroll ARGENTINA | 8 participants | 9 participants | 15 participants | 11 participants | 43 participants |
| Region Enroll BULGARIA | 4 participants | 2 participants | 1 participants | 3 participants | 10 participants |
| Region Enroll COLOMBIA | 4 participants | 15 participants | 8 participants | 15 participants | 42 participants |
| Region Enroll CZECH REPUBLIC | 7 participants | 8 participants | 8 participants | 7 participants | 30 participants |
| Region Enroll ESTONIA | 6 participants | 6 participants | 3 participants | 5 participants | 20 participants |
| Region Enroll GREECE | 1 participants | 1 participants | 3 participants | 4 participants | 9 participants |
| Region Enroll INDIA | 13 participants | 28 participants | 31 participants | 22 participants | 94 participants |
| Region Enroll ITALY | 2 participants | 3 participants | 3 participants | 1 participants | 9 participants |
| Region Enroll LATVIA | 3 participants | 7 participants | 6 participants | 10 participants | 26 participants |
| Region Enroll MALAYSIA | 9 participants | 7 participants | 11 participants | 7 participants | 34 participants |
| Region Enroll MEXICO | 12 participants | 20 participants | 26 participants | 18 participants | 76 participants |
| Region Enroll PERU | 16 participants | 36 participants | 30 participants | 37 participants | 119 participants |
| Region Enroll POLAND | 1 participants | 18 participants | 14 participants | 10 participants | 43 participants |
| Region Enroll PORTUGAL | 1 participants | 1 participants | 0 participants | 2 participants | 4 participants |
| Region Enroll RUSSIAN FEDERATION | 15 participants | 34 participants | 28 participants | 22 participants | 99 participants |
| Region Enroll SINGAPORE | 3 participants | 5 participants | 3 participants | 3 participants | 14 participants |
| Region Enroll SLOVAKIA | 12 participants | 16 participants | 21 participants | 17 participants | 66 participants |
| Region Enroll SWEDEN | 3 participants | 3 participants | 2 participants | 4 participants | 12 participants |
| Region Enroll THAILAND | 4 participants | 9 participants | 11 participants | 8 participants | 32 participants |
| Region Enroll TURKEY | 1 participants | 5 participants | 11 participants | 9 participants | 26 participants |
| Region Enroll UKRAINE | 8 participants | 24 participants | 29 participants | 30 participants | 91 participants |
| Region Enroll UNITED STATES | 50 participants | 111 participants | 103 participants | 121 participants | 385 participants |
| Sex: Female, Male Female | 89 Participants | 194 Participants | 202 Participants | 194 Participants | 679 Participants |
| Sex: Female, Male Male | 94 Participants | 174 Participants | 165 Participants | 172 Participants | 605 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 31 / 183 | 55 / 368 | 45 / 367 | 42 / 366 | 55 / 183 | 108 / 368 | 101 / 367 | 109 / 366 |
| serious Total, serious adverse events | 4 / 183 | 12 / 368 | 10 / 367 | 8 / 366 | 7 / 183 | 15 / 368 | 12 / 367 | 18 / 366 |
Outcome results
Primary
Change in HbA1c From Baseline to Week 26
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change.
Time frame: Day 1 (Baseline) and Week 26
Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Sitagliptin | Change in HbA1c From Baseline to Week 26 | -0.17 Percent | Standard Error 0.06 |
| Canagliflozin 100 mg | Change in HbA1c From Baseline to Week 26 | -0.79 Percent | Standard Error 0.044 |
| Canagliflozin 300 mg | Change in HbA1c From Baseline to Week 26 | -0.94 Percent | Standard Error 0.044 |
| Sitagliptin 100 mg | Change in HbA1c From Baseline to Week 26 | -0.82 Percent | Standard Error 0.044 |
p-value: <0.00195% CI: [-0.758, -0.481]ANCOVA
p-value: <0.00195% CI: [-0.914, -0.636]ANCOVA
95% CI: [-0.795, -0.516]ANCOVA
Secondary
Change in 2-hour Post-prandial Glucose From Baseline to Week 26
The table below shows the least-squares (LS) mean change in 2-hour post-prandial glucose from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change.
Time frame: Day 1 (Baseline) and Week 26
Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Sitagliptin | Change in 2-hour Post-prandial Glucose From Baseline to Week 26 | -9.79 mg/dL | Standard Error 4.86 |
| Canagliflozin 100 mg | Change in 2-hour Post-prandial Glucose From Baseline to Week 26 | -47.9 mg/dL | Standard Error 3.305 |
| Canagliflozin 300 mg | Change in 2-hour Post-prandial Glucose From Baseline to Week 26 | -57.1 mg/dL | Standard Error 3.356 |
| Sitagliptin 100 mg | Change in 2-hour Post-prandial Glucose From Baseline to Week 26 | -49.3 mg/dL | Standard Error 3.34 |
p-value: <0.00195% CI: [-49.14, -27.16]ANCOVA
p-value: <0.00195% CI: [-58.4, -36.29]ANCOVA
95% CI: [-50.56, -28.55]ANCOVA
Secondary
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26
The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change.
Time frame: Day 1 (Baseline) and Week 26
Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Sitagliptin | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 | 2.47 mg/dL | Standard Error 2.576 |
| Canagliflozin 100 mg | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 | -27.3 mg/dL | Standard Error 1.873 |
| Canagliflozin 300 mg | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 | -37.8 mg/dL | Standard Error 1.893 |
| Sitagliptin 100 mg | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 | -20.2 mg/dL | Standard Error 1.908 |
p-value: <0.00195% CI: [-35.76, -23.81]ANCOVA
p-value: <0.00195% CI: [-46.25, -34.26]ANCOVA
95% CI: [-28.7, -16.69]ANCOVA
Secondary
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52
The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change.
Time frame: Day 1 (Baseline) and Week 52
Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Sitagliptin | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52 | -26.2 mg/dL | Standard Error 1.814 |
| Canagliflozin 100 mg | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52 | -35.2 mg/dL | Standard Error 1.833 |
| Canagliflozin 300 mg | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52 | -17.7 mg/dL | Standard Error 1.848 |
p-value: <0.00195% CI: [-13.25, -3.857]ANCOVA
p-value: <0.00195% CI: [-22.24, -12.81]ANCOVA
Secondary
Change in HbA1c From Baseline to Week 52
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change.
Time frame: Day 1 (Baseline) and Week 52
Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Sitagliptin | Change in HbA1c From Baseline to Week 52 | -0.73 Percent | Standard Error 0.047 |
| Canagliflozin 100 mg | Change in HbA1c From Baseline to Week 52 | -0.88 Percent | Standard Error 0.047 |
| Canagliflozin 300 mg | Change in HbA1c From Baseline to Week 52 | -0.73 Percent | Standard Error 0.047 |
95% CI: [-0.119, 0.122]ANCOVA
95% CI: [-0.273, -0.031]ANCOVA
Secondary
Change in Systolic Blood Pressure (SBP) From Baseline to Week 26
The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change.
Time frame: Day 1 (Baseline) and Week 26
Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Sitagliptin | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 | 1.52 mmHg | Standard Error 0.829 |
| Canagliflozin 100 mg | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 | -3.84 mmHg | Standard Error 0.602 |
| Canagliflozin 300 mg | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 | -5.06 mmHg | Standard Error 0.605 |
| Sitagliptin 100 mg | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 | -1.83 mmHg | Standard Error 0.611 |
p-value: <0.00195% CI: [-7.28, -3.439]ANCOVA
p-value: <0.00195% CI: [-8.504, -4.653]ANCOVA
95% CI: [-5.273, -1.413]ANCOVA
Secondary
Change in Systolic Blood Pressure (SBP) From Baseline to Week 52
The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change.
Time frame: Day 1 (Baseline) and Week 52
Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Sitagliptin | Change in Systolic Blood Pressure (SBP) From Baseline to Week 52 | -3.53 mmHg | Standard Error 0.615 |
| Canagliflozin 100 mg | Change in Systolic Blood Pressure (SBP) From Baseline to Week 52 | -4.65 mmHg | Standard Error 0.618 |
| Canagliflozin 300 mg | Change in Systolic Blood Pressure (SBP) From Baseline to Week 52 | -0.66 mmHg | Standard Error 0.625 |
p-value: <0.00195% CI: [-4.464, -1.276]ANCOVA
p-value: <0.00195% CI: [-5.589, -2.389]ANCOVA
Secondary
Percentage of Patients With HbA1c <7% at Week 26
The table below shows the percentage of patients with HbA1c \<7% at Week 26 in each treatment group. The statistical analyses show the treatment differences between each canagliflozin or sitagliptin group and placebo.
Time frame: Week 26
Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Sitagliptin | Percentage of Patients With HbA1c <7% at Week 26 | 29.8 Percentage of patients |
| Canagliflozin 100 mg | Percentage of Patients With HbA1c <7% at Week 26 | 45.5 Percentage of patients |
| Canagliflozin 300 mg | Percentage of Patients With HbA1c <7% at Week 26 | 57.8 Percentage of patients |
| Sitagliptin 100 mg | Percentage of Patients With HbA1c <7% at Week 26 | 54.5 Percentage of patients |
p-value: <0.00195% CI: [1.5, 3.5]Regression, Logistic
p-value: <0.00195% CI: [2.85, 6.77]Regression, Logistic
Secondary
Percent Change in Body Weight From Baseline to Week 26
The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change.
Time frame: Day 1 (Baseline) and Week 26
Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Sitagliptin | Percent Change in Body Weight From Baseline to Week 26 | -1.2 Percent change | Standard Error 0.3 |
| Canagliflozin 100 mg | Percent Change in Body Weight From Baseline to Week 26 | -3.7 Percent change | Standard Error 0.2 |
| Canagliflozin 300 mg | Percent Change in Body Weight From Baseline to Week 26 | -4.2 Percent change | Standard Error 0.2 |
| Sitagliptin 100 mg | Percent Change in Body Weight From Baseline to Week 26 | -1.2 Percent change | Standard Error 0.2 |
p-value: <0.00195% CI: [-3.1, -1.9]ANCOVA
p-value: <0.00195% CI: [-3.5, -2.3]ANCOVA
95% CI: [-0.6, 0.6]ANCOVA
Secondary
Percent Change in Body Weight From Baseline to Week 52
The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change.
Time frame: Day 1 (Baseline) and Week 52
Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Sitagliptin | Percent Change in Body Weight From Baseline to Week 52 | -3.8 Percent change | Standard Error 0.2 |
| Canagliflozin 100 mg | Percent Change in Body Weight From Baseline to Week 52 | -4.2 Percent change | Standard Error 0.2 |
| Canagliflozin 300 mg | Percent Change in Body Weight From Baseline to Week 52 | -1.3 Percent change | Standard Error 0.2 |
p-value: <0.00195% CI: [-3, -1.8]ANCOVA
p-value: <0.00195% CI: [-3.4, -2.3]ANCOVA
Secondary
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change.
Time frame: Day 1 (Baseline) and Week 26
Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Sitagliptin | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 | 3.7 Percent change | Standard Error 1.3 |
| Canagliflozin 100 mg | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 | 10.4 Percent change | Standard Error 0.9 |
| Canagliflozin 300 mg | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 | 12.1 Percent change | Standard Error 1 |
| Sitagliptin 100 mg | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 | 5.0 Percent change | Standard Error 1 |
p-value: <0.00195% CI: [3.6, 9.7]ANCOVA
p-value: <0.00195% CI: [5.4, 11.5]ANCOVA
95% CI: [-1.7, 4.4]ANCOVA
Secondary
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52
The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change.
Time frame: Day 1 (Baseline) and Week 52
Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Sitagliptin | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 | 11.2 Percent change | Standard Error 1 |
| Canagliflozin 100 mg | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 | 13.3 Percent change | Standard Error 1.1 |
| Canagliflozin 300 mg | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 | 6.0 Percent change | Standard Error 1.1 |
p-value: <0.00195% CI: [2.5, 8]ANCOVA
p-value: <0.00195% CI: [4.5, 10.1]ANCOVA
Secondary
Percent Change in Triglycerides From Baseline to Week 26
The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean percent change.
Time frame: Day 1 (Baseline) and Week 26
Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Sitagliptin | Percent Change in Triglycerides From Baseline to Week 26 | 3.2 Percent change | Standard Error 3.6 |
| Canagliflozin 100 mg | Percent Change in Triglycerides From Baseline to Week 26 | 1.6 Percent change | Standard Error 2.6 |
| Canagliflozin 300 mg | Percent Change in Triglycerides From Baseline to Week 26 | -1.4 Percent change | Standard Error 2.6 |
| Sitagliptin 100 mg | Percent Change in Triglycerides From Baseline to Week 26 | 1.0 Percent change | Standard Error 2.7 |
p-value: 0.70295% CI: [-9.9, 6.7]ANCOVA
p-value: 0.27495% CI: [-13, 3.7]ANCOVA
95% CI: [-10.6, 6.1]ANCOVA
Secondary
Percent Change in Triglycerides From Baseline to Week 52
The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change.
Time frame: Day 1 (Baseline) and Week 52
Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Sitagliptin | Percent Change in Triglycerides From Baseline to Week 52 | 1.9 Percent change | Standard Error 2.4 |
| Canagliflozin 100 mg | Percent Change in Triglycerides From Baseline to Week 52 | 2.7 Percent change | Standard Error 2.4 |
| Canagliflozin 300 mg | Percent Change in Triglycerides From Baseline to Week 52 | -0.4 Percent change | Standard Error 2.5 |
p-value: 0.46695% CI: [-3.9, 8.5]ANCOVA
p-value: 0.32395% CI: [-3.1, 9.4]ANCOVA