| Trial | Outcome |
|---|
| NCT00642278 (6) [back to overview] | Percent Change in Body Weight From Baseline to Week 12 |
| NCT00642278 (6) [back to overview] | Absolute Change in Body Weight From Baseline to Week 12 |
| NCT00642278 (6) [back to overview] | Change in Overnight Urine Glucose/Creatinine Ratio From Baseline to Week 12 |
| NCT00642278 (6) [back to overview] | Change in HbA1c From Baseline to Week 12 |
| NCT00642278 (6) [back to overview] | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 12 |
| NCT00642278 (6) [back to overview] | Percentage of Patients With Symptoms of Hypoglycemia |
| NCT00650806 (8) [back to overview] | Change in Waist Circumference From Baseline to Week 12 |
| NCT00650806 (8) [back to overview] | Change in Hip Circumference From Baseline to Week 12 |
| NCT00650806 (8) [back to overview] | Change in Body Mass Index (BMI) From Baseline to Week 12 |
| NCT00650806 (8) [back to overview] | Absolute Change in Body Weight From Baseline to Week 12 |
| NCT00650806 (8) [back to overview] | Percentage of Patients Who Lost at Least 5% of Their Initial Body Weight by Week 12 |
| NCT00650806 (8) [back to overview] | Percentage of Patients Who Lost at Least 10% of Their Initial Body Weight by Week 12 |
| NCT00650806 (8) [back to overview] | Percent Change in Body Weight From Baseline to Week 12 |
| NCT00650806 (8) [back to overview] | Change in Waist/Hip Ratio From Baseline to Week 12 |
| NCT00968812 (4) [back to overview] | Change in HbA1c From Baseline to Week 104 |
| NCT00968812 (4) [back to overview] | Change in HbA1c From Baseline to Week 52 |
| NCT00968812 (4) [back to overview] | Percent Change in Body Weight From Baseline to Week 52 |
| NCT00968812 (4) [back to overview] | Percentage of Patients Experiencing at Least 1 Hypoglycemic Event From Baseline to Week 52 |
| NCT01032629 (13) [back to overview] | Change From Baseline in Homeostasis Model Assessment 2 Steady-State Beta-Cell Function (HOMA2-%B) at the End-of-Treatment (EOT) |
| NCT01032629 (13) [back to overview] | Change From Baseline in Glycated Hemoglobin (HbA1c) at End-of-Treatment |
| NCT01032629 (13) [back to overview] | Change From Baseline in Fasting Plasma Glucose (FPG) Levels at End-of-Treatment |
| NCT01032629 (13) [back to overview] | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at End-of-Treatment |
| NCT01032629 (13) [back to overview] | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at End-of-Treatment |
| NCT01032629 (13) [back to overview] | Change From Baseline in Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) Levels at End-of-Treatment |
| NCT01032629 (13) [back to overview] | Percentage of Participants With Progression of Albuminuria at the End-of-Treatment |
| NCT01032629 (13) [back to overview] | Percent Change From Baseline in Body Weight at End-of-Treatment |
| NCT01032629 (13) [back to overview] | Major Adverse Cardiovascular Events (MACE) Composite of Cardiovascular (CV) Death, Non-Fatal Myocardial Infarction (MI), and Non-Fatal Stroke |
| NCT01032629 (13) [back to overview] | Change From Baseline in Urinary Albumin/Creatinine Ratio at End-of-Treatment |
| NCT01032629 (13) [back to overview] | Change From Baseline in Triglycerides Levels at End-of-Treatment |
| NCT01032629 (13) [back to overview] | Change From Baseline in Proinsulin/Insulin (PI/I) Ratio at the End-of-Treatment |
| NCT01032629 (13) [back to overview] | Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) to High-Density Lipoprotein-Cholesterol (HDL-C) Ratio at End-of-Treatment |
| NCT01064414 (3) [back to overview] | Change in HbA1c From Baseline to Week 26 |
| NCT01064414 (3) [back to overview] | Percentage of Patients With HbA1c <7% at Week 26 |
| NCT01064414 (3) [back to overview] | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 |
| NCT01081834 (16) [back to overview] | Change in HbA1c From Baseline to Week 26 (Main Study) |
| NCT01081834 (16) [back to overview] | Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (High Glycemic Substudy) |
| NCT01081834 (16) [back to overview] | Percent Change in Body Weight From Baseline to Week 26 (Main Study) |
| NCT01081834 (16) [back to overview] | Percent Change in Body Weight From Baseline to Week 26 (High Glycemic Substudy) |
| NCT01081834 (16) [back to overview] | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (Main Study) |
| NCT01081834 (16) [back to overview] | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (High Glycemic Substudy) |
| NCT01081834 (16) [back to overview] | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (High Glycemic Substudy) |
| NCT01081834 (16) [back to overview] | Change in HbA1c From Baseline to Week 26 (High Glycemic Substudy) |
| NCT01081834 (16) [back to overview] | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (Main Study) |
| NCT01081834 (16) [back to overview] | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (High Glycemic Substudy) |
| NCT01081834 (16) [back to overview] | Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (Main Study) |
| NCT01081834 (16) [back to overview] | Percentage of Patients With HbA1c <7% at Week 26 (Main Study) |
| NCT01081834 (16) [back to overview] | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (Main Study) |
| NCT01081834 (16) [back to overview] | Percent Change in Triglycerides From Baseline to Week 26 (High Glycemic Substudy) |
| NCT01081834 (16) [back to overview] | Percent Change in Triglycerides From Baseline to Week 26 (Main Study) |
| NCT01081834 (16) [back to overview] | Percentage of Patients With HbA1c <7% at Week 26 (High Glycemic Substudy) |
| NCT01106625 (7) [back to overview] | Percent Change in Triglycerides From Baseline to Week 26 |
| NCT01106625 (7) [back to overview] | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 |
| NCT01106625 (7) [back to overview] | Percent Change in Body Weight From Baseline to Week 26 |
| NCT01106625 (7) [back to overview] | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 |
| NCT01106625 (7) [back to overview] | Percentage of Patients With HbA1c <7% at Week 26 |
| NCT01106625 (7) [back to overview] | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 |
| NCT01106625 (7) [back to overview] | Change in HbA1c From Baseline to Week 26 |
| NCT01106651 (14) [back to overview] | Change in HbA1c From Baseline to Week 26 |
| NCT01106651 (14) [back to overview] | Percent Change in Body Weight From Baseline to Week 26 |
| NCT01106651 (14) [back to overview] | Percentage of Patients With HbA1c <7% at Week 26 |
| NCT01106651 (14) [back to overview] | 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 |
| NCT01106651 (14) [back to overview] | Percent Change in Triglycerides From Baseline to Week 26 |
| NCT01106651 (14) [back to overview] | Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26 |
| NCT01106651 (14) [back to overview] | Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26 |
| NCT01106651 (14) [back to overview] | Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26 |
| NCT01106651 (14) [back to overview] | Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26 |
| NCT01106651 (14) [back to overview] | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 |
| NCT01106651 (14) [back to overview] | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 |
| NCT01106651 (14) [back to overview] | 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 |
| NCT01106651 (14) [back to overview] | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 |
| NCT01106651 (14) [back to overview] | 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 |
| NCT01106677 (14) [back to overview] | Change in 2-hour Post-prandial Glucose From Baseline to Week 26 |
| NCT01106677 (14) [back to overview] | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 |
| NCT01106677 (14) [back to overview] | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 |
| NCT01106677 (14) [back to overview] | Percent Change in Triglycerides From Baseline to Week 26 |
| NCT01106677 (14) [back to overview] | Change in Systolic Blood Pressure (SBP) From Baseline to Week 52 |
| NCT01106677 (14) [back to overview] | Percentage of Patients With HbA1c <7% at Week 26 |
| NCT01106677 (14) [back to overview] | Change in HbA1c From Baseline to Week 52 |
| NCT01106677 (14) [back to overview] | Percent Change in Body Weight From Baseline to Week 26 |
| NCT01106677 (14) [back to overview] | Percent Change in Body Weight From Baseline to Week 52 |
| NCT01106677 (14) [back to overview] | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 |
| NCT01106677 (14) [back to overview] | Change in HbA1c From Baseline to Week 26 |
| NCT01106677 (14) [back to overview] | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52 |
| NCT01106677 (14) [back to overview] | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 |
| NCT01106677 (14) [back to overview] | Percent Change in Triglycerides From Baseline to Week 52 |
| NCT01106690 (8) [back to overview] | Change in Homeostasis Model Assessment (HOMA2-%B) From Baseline to Week 26 |
| NCT01106690 (8) [back to overview] | Change in HbA1c From Baseline to Week 26 |
| NCT01106690 (8) [back to overview] | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 |
| NCT01106690 (8) [back to overview] | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 |
| NCT01106690 (8) [back to overview] | Percentage of Patients With HbA1c <7% at Week 26 |
| NCT01106690 (8) [back to overview] | Percent Change in Triglycerides From Baseline to Week 26 |
| NCT01106690 (8) [back to overview] | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 |
| NCT01106690 (8) [back to overview] | Percent Change in Body Weight From Baseline to Week 26 |
| NCT01137812 (7) [back to overview] | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52 |
| NCT01137812 (7) [back to overview] | Percent Change in Body Weight From Baseline to Week 52 |
| NCT01137812 (7) [back to overview] | Change in Systolic Blood Pressure (SBP) From Baseline to Week 52 |
| NCT01137812 (7) [back to overview] | Change in HbA1c From Baseline to Week 52 |
| NCT01137812 (7) [back to overview] | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52 |
| NCT01137812 (7) [back to overview] | Percentage of Patients With HbA1c <7% at Week 52 |
| NCT01137812 (7) [back to overview] | Percent Change in Triglycerides From Baseline to Week 52 |
| NCT01340664 (4) [back to overview] | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18 |
| NCT01340664 (4) [back to overview] | Percentage of Patients With HbA1c <7% at Week 18 |
| NCT01340664 (4) [back to overview] | Change in HbA1c From Baseline to Week 18 |
| NCT01340664 (4) [back to overview] | Percent Change in Body Weight From Baseline to Week 18 |
| NCT01381900 (5) [back to overview] | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18 |
| NCT01381900 (5) [back to overview] | Change in Glycosylated Hemoglobin (HbA1c) From Baseline to Week 18 |
| NCT01381900 (5) [back to overview] | Percent Change in Body Weight From Baseline to Week 18 |
| NCT01381900 (5) [back to overview] | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <7% at Week 18 |
| NCT01381900 (5) [back to overview] | Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <6.5% at Week 18 |
| NCT01809327 (7) [back to overview] | Change in Systolic Blood Pressure From Baseline at Week 26 |
| NCT01809327 (7) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (AEs) |
| NCT01809327 (7) [back to overview] | Percent Change in Body Weight From Baseline to Week 26 |
| NCT01809327 (7) [back to overview] | Percent Change in Fasting High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 |
| NCT01809327 (7) [back to overview] | Percent Change in Triglycerides From Baseline to Week 26 |
| NCT01809327 (7) [back to overview] | Percentage of Participants With Glycated Hemoglobin (HbAIc) Less Than 7 Percent at Week 26 |
| NCT01809327 (7) [back to overview] | Change in Glycated Hemoglobin (HbA1c) From Baseline at Week 26 |
| NCT01939496 (15) [back to overview] | Change From Baseline in Standing Heart Rate (HR) to Day 2, to Week 3, and to Week 6 |
| NCT01939496 (15) [back to overview] | Change From Baseline in Standing Office Blood Pressure (BP) to Day 2, to Week 3, and to Week 6 |
| NCT01939496 (15) [back to overview] | Change From Baseline in the Difference in Seated Heart Rate (HR) and Standing HR to Day 2, to Week 3, and to Week 6 |
| NCT01939496 (15) [back to overview] | Change From Baseline in the Difference in Seated Office Blood Pressure (BP) and Standing Office BP to Day 2, to Week 3, and to Week 6 |
| NCT01939496 (15) [back to overview] | Change From Baseline in the Mean 24-Hour Diastolic Blood Pressure (DBP) to Day 2 and to Week 6 |
| NCT01939496 (15) [back to overview] | Change From Baseline in the Mean 24-Hour Systolic Blood Pressure (SBP) to Week 6 |
| NCT01939496 (15) [back to overview] | Change From Baseline in Mean Nighttime Systolic Blood Pressure (SBP) to Day 2 and to Week 6 |
| NCT01939496 (15) [back to overview] | Change From Baseline in Seated Heart Rate (HR) to Day 2, to Week 3, and to Week 6 |
| NCT01939496 (15) [back to overview] | Change From Baseline in Seated Office Blood Pressure (BP) to Day 2, to Week 3, and to Week 6 |
| NCT01939496 (15) [back to overview] | Change From Baseline in Mean 24-Hour Systolic Blood Pressure (SBP) to Day 2 |
| NCT01939496 (15) [back to overview] | Change From Baseline in Body Weight to Week 6 |
| NCT01939496 (15) [back to overview] | Change From Baseline in Fasting Plasma Glucose (FPG) to Week 6 |
| NCT01939496 (15) [back to overview] | Change From Baseline in Mean Daytime Diastolic Blood Pressure (DBP) to Day 2 and to Week 6 |
| NCT01939496 (15) [back to overview] | Change From Baseline in Mean Daytime Systolic Blood Pressure (SBP) to Day 2 and to Week 6 |
| NCT01939496 (15) [back to overview] | Change From Baseline in Mean Nighttime Diastolic Blood Pressure (DBP) to Day 2 and to Week 6 |
| NCT01989754 (3) [back to overview] | Progression of Albuminuria |
| NCT01989754 (3) [back to overview] | Composite of Cardiovascular (CV) Death Events or Hospitalization for Heart Failure |
| NCT01989754 (3) [back to overview] | Cardiovascular (CV) Death |
| NCT02025907 (5) [back to overview] | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 |
| NCT02025907 (5) [back to overview] | Percentage of Participants With HbA1c Less Than (<) 7.0 Percent at Week 26 |
| NCT02025907 (5) [back to overview] | Percent Change From Baseline in Body Weight at Week 26 |
| NCT02025907 (5) [back to overview] | Change From Baseline in Systolic Blood Pressure (SBP) at Week 26 |
| NCT02025907 (5) [back to overview] | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 |
| NCT02065791 (8) [back to overview] | Cardiovascular (CV) Death |
| NCT02065791 (8) [back to overview] | Composite Endpoint of CV Death and Hospitalized Heart Failure (HHF) |
| NCT02065791 (8) [back to overview] | CV Composite Endpoint |
| NCT02065791 (8) [back to overview] | Hospitalized Heart Failure (HHF) |
| NCT02065791 (8) [back to overview] | Major Adverse Cardiac Event (MACE) |
| NCT02065791 (8) [back to overview] | Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (ESKD), and Renal or Cardiovascular (CV) Death |
| NCT02065791 (8) [back to overview] | All-cause Mortality |
| NCT02065791 (8) [back to overview] | Renal Composite Endpoint |
| NCT02139943 (2) [back to overview] | Percentage of Participants With Hemoglobin A1c (HbA1c) Reduction Greater Than or Equal to (>=) 0.4 Percent (%) and no Increase in Body Weight |
| NCT02139943 (2) [back to overview] | Percentage of Participants With Adverse Events |
| NCT02220907 (4) [back to overview] | Change From Baseline in Fasting Plasma Glucose Level |
| NCT02220907 (4) [back to overview] | Percentage Change in Body Weight From Baseline |
| NCT02220907 (4) [back to overview] | Number of Participants With Adverse Events |
| NCT02220907 (4) [back to overview] | Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) |
| NCT02220920 (5) [back to overview] | "Percentage of Participants With Adverse Events and Hypoglycemia and Blood Glucose Decreased" |
| NCT02220920 (5) [back to overview] | Change in Blood Pressure |
| NCT02220920 (5) [back to overview] | Change in Fasting Plasma Glucose |
| NCT02220920 (5) [back to overview] | Change in HbA1c From Baseline |
| NCT02220920 (5) [back to overview] | Percent Change in Body Weight |
| NCT02227849 (5) [back to overview] | Safety and Tolerability Assessed by Adverse Events (Number of Participants Experiencing With Adverse Events) |
| NCT02227849 (5) [back to overview] | Change in Blood Pressure |
| NCT02227849 (5) [back to overview] | Percentage Change in Body Weight |
| NCT02227849 (5) [back to overview] | Change in Percentage of HbA1c |
| NCT02227849 (5) [back to overview] | Change in Fasting Plasma Glucose |
| NCT02243202 (7) [back to overview] | Change From Baseline in Systolic Blood Pressure at Week 26 |
| NCT02243202 (7) [back to overview] | Change From Baseline in Diastolic Blood Pressure (DBP) at Week 26 |
| NCT02243202 (7) [back to overview] | Absolute Change From Baseline in Body Weight at Week 26 |
| NCT02243202 (7) [back to overview] | Percentage of Participants With Weight Loss More Than Equal to (>=) 5 Percent at Week 26 |
| NCT02243202 (7) [back to overview] | Percentage of Participants With Weight Loss More Than Equal to (>=) 10 Percent at Week 26 |
| NCT02243202 (7) [back to overview] | Change From Baseline in Pulse Rate at Week 26 |
| NCT02243202 (7) [back to overview] | Percent Change From Baseline in Body Weight at Week 26 |
| NCT02324842 (8) [back to overview] | Change in 24-hour Blood Pressure at Study End Compared to Baseline. |
| NCT02324842 (8) [back to overview] | HbA1c at 4 Months |
| NCT02324842 (8) [back to overview] | Fasting Plasma Glucose (FPG) at 4 Months |
| NCT02324842 (8) [back to overview] | Change in Total Body Weight at Study End Compared to Baseline |
| NCT02324842 (8) [back to overview] | Change in Plasma Glucagon Concentration at the End of the Study Compared to Baseline |
| NCT02324842 (8) [back to overview] | Change in Matsuda Index of Insulin Sensitivity, Insulin Secretion, and Beta Cell Function During Oral Glucose Tolerance Test (OGTT) |
| NCT02324842 (8) [back to overview] | Change in Free Plasma Insulin at the End of the Study From Baseline Value |
| NCT02324842 (8) [back to overview] | Body Mass Index (BMI) at 4 Months |
| NCT02354222 (5) [back to overview] | Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) |
| NCT02354222 (5) [back to overview] | Percentage Change in Body Weight From Baseline |
| NCT02354222 (5) [back to overview] | Change From Baseline in the AUC(0-2h) for Postprandial Plasma Glucose (PPG) |
| NCT02354222 (5) [back to overview] | Change From Baseline in Fasting Plasma Glucose Level |
| NCT02354222 (5) [back to overview] | Change From Baseline in 2-hour Postprandial Plasma Glucose Level |
| NCT02354235 (5) [back to overview] | Percentage Change in Body Weight From Baseline |
| NCT02354235 (5) [back to overview] | Change From Baseline in 2-hour Postprandial Plasma Glucose Level |
| NCT02354235 (5) [back to overview] | Change From Baseline in the AUC(0-2h) for Postprandial Plasma Glucose (PPG) |
| NCT02354235 (5) [back to overview] | Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) |
| NCT02354235 (5) [back to overview] | Change From Baseline in Fasting Plasma Glucose Level |
| NCT02360774 (4) [back to overview] | Change in Body Composition, Measured Using DXA Scanning. |
| NCT02360774 (4) [back to overview] | Change in Body Weight |
| NCT02360774 (4) [back to overview] | Change in Glycemic Control |
| NCT02360774 (4) [back to overview] | Change in Resting Energy Expenditure, Measured Using Indirect Calorimetery |
| NCT02462421 (6) [back to overview] | Canagliflozin-induced Change in Urinary Excretion of Sodium |
| NCT02462421 (6) [back to overview] | Change in Fractional Excretion of Uric Acid (the Difference Between Data After Administration of Canagliflozin Minus Data Before Administration of Canagliflozin) |
| NCT02462421 (6) [back to overview] | Urinary Excretion of Glucose (Measured During the 24 Hours Following Administration of Canagliflozin) |
| NCT02462421 (6) [back to overview] | Canagliflozin-induced Change in Serum Creatinine |
| NCT02462421 (6) [back to overview] | Canagliflozin-induced Change in Fasting Plasma Glucose |
| NCT02462421 (6) [back to overview] | Canagliflozin-induced Change in Serum Uric Acid |
| NCT02597049 (11) [back to overview] | Change From Baseline in 6-Point Self-Monitored Plasma Glucose (SMPG) Profile at 24 Weeks |
| NCT02597049 (11) [back to overview] | Change From Baseline in Body Weight at 24 Weeks |
| NCT02597049 (11) [back to overview] | Change From Baseline in Fasting Serum Glucose (Central Laboratory) at 24 Weeks |
| NCT02597049 (11) [back to overview] | Number of Participants With Adjudicated Cardiovascular (CV) Events |
| NCT02597049 (11) [back to overview] | Percentage of Participants With HbA1c <7% |
| NCT02597049 (11) [back to overview] | Rate of Hypoglycemic Events Adjusted Per 30 Days |
| NCT02597049 (11) [back to overview] | Change From Baseline in the HbA1c at 24 Weeks (Efficacy Estimand) |
| NCT02597049 (11) [back to overview] | Change From Baseline in Hemoglobin A1c (HbA1c) at 24 Weeks (Treatment-regimen Estimand) |
| NCT02597049 (11) [back to overview] | Change From Baseline in Fasting Glucagon at 24 Weeks |
| NCT02597049 (11) [back to overview] | Number of Participants Requiring Rescue Therapy Due to Severe Persistent Hyperglycemia |
| NCT02597049 (11) [back to overview] | Number of Participants With Adjudicated Acute Pancreatitis Events |
| NCT02622113 (4) [back to overview] | Percentage Change in Body Weight |
| NCT02622113 (4) [back to overview] | Change in Percentage of HbA1c |
| NCT02622113 (4) [back to overview] | Change in Fasting Plasma Glucose |
| NCT02622113 (4) [back to overview] | Safety and Tolerability Assessed by Adverse Events (Number of Participants Experiencing With Adverse Events) |
| NCT02673138 (4) [back to overview] | Differences in Free Fatty Acid Levels Following Interruption of Basal Subcutaneous Insulin Infusion |
| NCT02673138 (4) [back to overview] | Differences in Plasma Glucose Levels Following the Interruption of Basal Subcutaneous Infusion of Insulin |
| NCT02673138 (4) [back to overview] | Differences in BHB (Beta-hydroxybutyrate) Levels Following Interruption of Basal |
| NCT02673138 (4) [back to overview] | Differences in Glucagon Levels Following the Interruption of the Basal Subcutaneous Insulin Infusion |
| NCT02912455 (17) [back to overview] | Change at Six Months Versus Baseline in Hemoglobin A1c Value (%) |
| NCT02912455 (17) [back to overview] | Change in Adiponectin Levels at 6 Months Compared to Randomization |
| NCT02912455 (17) [back to overview] | Change in Body Weight at Six Months Compared to Baseline |
| NCT02912455 (17) [back to overview] | Change in CRP Levels at 6 Months Compared to Baseline |
| NCT02912455 (17) [back to overview] | Change in Diastolic Blood Pressure at Six Months Compared to Baseline |
| NCT02912455 (17) [back to overview] | Change in Fasting Glucose From Randomization |
| NCT02912455 (17) [back to overview] | Change in Percentage of Truncal Fat |
| NCT02912455 (17) [back to overview] | Change in Spine Bone Mineral Density |
| NCT02912455 (17) [back to overview] | Change in Percentage of Lean Mass |
| NCT02912455 (17) [back to overview] | Change in Percentage of Gynoid Fat |
| NCT02912455 (17) [back to overview] | Change in Percentage of Android Fat |
| NCT02912455 (17) [back to overview] | Change in Percent Body Fat as Measured by DEXA Scan at 6 Months Compared to Randomization |
| NCT02912455 (17) [back to overview] | Change in Leptin Levels at 6 Months Compared to Baseline |
| NCT02912455 (17) [back to overview] | Number of Participants Who Reported Hypoglycemia From Each Group (at a Frequency of 1 Episode) |
| NCT02912455 (17) [back to overview] | Change in Leg Bone Mineral Density |
| NCT02912455 (17) [back to overview] | Change in Total Cholesterol |
| NCT02912455 (17) [back to overview] | Change in Systolic Blood Pressure at 6 Months Compared to Baseline |
| NCT02920918 (2) [back to overview] | Change From Baseline Ventilatory Efficiency at 12 Weeks |
| NCT02920918 (2) [back to overview] | Change From Baseline Aerobic Exercise Capacity at 12 Weeks |
| NCT02964585 (18) [back to overview] | Glycemic Control |
| NCT02964585 (18) [back to overview] | Glycemic Control (HbA1C) |
| NCT02964585 (18) [back to overview] | Microalbumin |
| NCT02964585 (18) [back to overview] | Pulse Wave Velocity |
| NCT02964585 (18) [back to overview] | Resting Metabolic Rate (RMR) |
| NCT02964585 (18) [back to overview] | Serum Endothelial Inflammatory Markers (2) |
| NCT02964585 (18) [back to overview] | Augmentation Index (Pulse Wave Analysis) |
| NCT02964585 (18) [back to overview] | Body Fat Percentage |
| NCT02964585 (18) [back to overview] | eGFR |
| NCT02964585 (18) [back to overview] | Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Proliferation) |
| NCT02964585 (18) [back to overview] | Fasting Lipid Profile |
| NCT02964585 (18) [back to overview] | Creatinine (Urine) |
| NCT02964585 (18) [back to overview] | BMI |
| NCT02964585 (18) [back to overview] | Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Counts) |
| NCT02964585 (18) [back to overview] | Serum Endothelial Inflammatory Markers (1) |
| NCT02964585 (18) [back to overview] | Kidney Function Markers |
| NCT02964585 (18) [back to overview] | Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Protein Expression) |
| NCT02964585 (18) [back to overview] | Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Percentages) |
| NCT03136484 (61) [back to overview] | Change in Total Fat Mass (kg) |
| NCT03136484 (61) [back to overview] | Change in SMPG- Mean Postprandial Increment Over All Meals |
| NCT03136484 (61) [back to overview] | Change in SMPG (Self-measured Plasma Glucose)- Mean 7-point Profile |
| NCT03136484 (61) [back to overview] | Change in SF-36: Physical Component Summary (PCS) |
| NCT03136484 (61) [back to overview] | Change in SF-36: Mental Component Summary (MCS) |
| NCT03136484 (61) [back to overview] | Change in Ratio Between Total Fat Mass and Total Lean Mass |
| NCT03136484 (61) [back to overview] | Change in Pulse |
| NCT03136484 (61) [back to overview] | Participants Who Achieved Weight Loss ≥5% (Yes/no) |
| NCT03136484 (61) [back to overview] | Participants Who Achieved Weight Loss ≥3% (Yes/no) |
| NCT03136484 (61) [back to overview] | Participants Who Achieved Weight Loss ≥10% (Yes/no) |
| NCT03136484 (61) [back to overview] | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥5% (Yes/no) |
| NCT03136484 (61) [back to overview] | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥3% (Yes/no) |
| NCT03136484 (61) [back to overview] | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥10% (Yes/no) |
| NCT03136484 (61) [back to overview] | Participants Who Achieved HbA1c Reduction ≥1% (Yes/no) |
| NCT03136484 (61) [back to overview] | Participants Who Achieved HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/no) |
| NCT03136484 (61) [back to overview] | Participants Who Achieved HbA1c ≤ 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE) Target (Yes/no) |
| NCT03136484 (61) [back to overview] | Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol), American Diabetes Association (ADA) Target (Yes/no) |
| NCT03136484 (61) [back to overview] | Change in Haematological Parameter- Leukocytes |
| NCT03136484 (61) [back to overview] | Change in Haematological Parameter- Haemoglobin |
| NCT03136484 (61) [back to overview] | Change in Haematological Parameter- Haematocrit |
| NCT03136484 (61) [back to overview] | Change in Haematological Parameter- Erythrocytes |
| NCT03136484 (61) [back to overview] | Change in FPG (Fasting Plasma Glucose) |
| NCT03136484 (61) [back to overview] | Change in Fasting Triglycerides |
| NCT03136484 (61) [back to overview] | Change in Fasting Total Cholesterol |
| NCT03136484 (61) [back to overview] | Change in Fasting LDL-cholesterol |
| NCT03136484 (61) [back to overview] | Change in Fasting HDL-cholesterol |
| NCT03136484 (61) [back to overview] | Change in Calcitonin |
| NCT03136484 (61) [back to overview] | Change in Body Weight (kg) |
| NCT03136484 (61) [back to overview] | Change in Body Mass Index (BMI) |
| NCT03136484 (61) [back to overview] | Change in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) |
| NCT03136484 (61) [back to overview] | Change in Short Form 36 Health Survey (SF-36): Sub-domains |
| NCT03136484 (61) [back to overview] | Change in Physical Examination |
| NCT03136484 (61) [back to overview] | Change in HbA1c |
| NCT03136484 (61) [back to overview] | Change in Biochemistry Parameter- Total Bilirubin |
| NCT03136484 (61) [back to overview] | Change in Biochemistry Parameter- Sodium |
| NCT03136484 (61) [back to overview] | Change in Biochemistry Parameter- Potassium |
| NCT03136484 (61) [back to overview] | Change in Biochemistry Parameter- Lipase |
| NCT03136484 (61) [back to overview] | Change in Biochemistry Parameter- eGFR |
| NCT03136484 (61) [back to overview] | Change in Haematological Parameter- Thrombocytes |
| NCT03136484 (61) [back to overview] | Change in Biochemistry Parameter- Calcium |
| NCT03136484 (61) [back to overview] | Change in Biochemistry Parameter- AST |
| NCT03136484 (61) [back to overview] | Change in Biochemistry Parameter- Amylase |
| NCT03136484 (61) [back to overview] | Change in ECG |
| NCT03136484 (61) [back to overview] | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately |
| NCT03136484 (61) [back to overview] | Change in Control of Eating Questionnaire (CoEQ): Domains |
| NCT03136484 (61) [back to overview] | Change in CoEQ: Individual Items |
| NCT03136484 (61) [back to overview] | Total Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes |
| NCT03136484 (61) [back to overview] | Total Number of Treatment Emergent Adverse Events (TEAEs) |
| NCT03136484 (61) [back to overview] | Percentage Change in Visceral Fat Mass (%) |
| NCT03136484 (61) [back to overview] | Percentage Change in Total Lean Mass (%) |
| NCT03136484 (61) [back to overview] | Percentage Change in Total Fat Mass (%) |
| NCT03136484 (61) [back to overview] | Eye Examination |
| NCT03136484 (61) [back to overview] | Change in Biochemistry Parameter- ALT |
| NCT03136484 (61) [back to overview] | Change in Biochemistry Parameter- ALP |
| NCT03136484 (61) [back to overview] | Change in Biochemistry Parameter- Albumin |
| NCT03136484 (61) [back to overview] | Participants With Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes |
| NCT03136484 (61) [back to overview] | Change in Waist Circumference |
| NCT03136484 (61) [back to overview] | Change in Visceral Fat Mass (kg) |
| NCT03136484 (61) [back to overview] | Percentage Change in Body Weight (%) |
| NCT03136484 (61) [back to overview] | Change in Total Lean Mass (kg) |
| NCT03136484 (61) [back to overview] | Change in Biochemistry Parameter- Creatinine |
| NCT03267576 (15) [back to overview] | Change From Baseline in Percentage of 2 Consecutive Glucose Readings With < 70 mg/dL |
| NCT03267576 (15) [back to overview] | Change From Baseline in Time Spent With Glucose Level < 70 mg/dL |
| NCT03267576 (15) [back to overview] | Change From Baseline in Time Spent With Glucose Level > 140 mg/dL |
| NCT03267576 (15) [back to overview] | Change From Baseline in Time Spent With Glucose Level > 180 mg/dL |
| NCT03267576 (15) [back to overview] | Change From Baseline in Time Spent With Glucose Level 70 to 139 mg/dL |
| NCT03267576 (15) [back to overview] | Percent Change From Baseline in Time During 24 Hours With Glucose 70 to 139 mg/dL |
| NCT03267576 (15) [back to overview] | Percent Change From Baseline in Time During 24 Hours With Glucose Greater Than (>) 140 mg/dL |
| NCT03267576 (15) [back to overview] | Percent Change From Baseline in Time During 24 Hours With Glucose Level > 180 mg/dL |
| NCT03267576 (15) [back to overview] | Percent Change From Baseline in Time During 24 Hours With Glucose Level Less Than (<) 70 mg/dL |
| NCT03267576 (15) [back to overview] | Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 1 |
| NCT03267576 (15) [back to overview] | Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 2 |
| NCT03267576 (15) [back to overview] | Change From Baseline in 2-hour Post-prandial Glucose (PPG) Levels |
| NCT03267576 (15) [back to overview] | Change From Baseline in Fasting Plasma Glucose Levels |
| NCT03267576 (15) [back to overview] | Change From Baseline in Glycemic Standard Deviation (SD) for 24-hour Glucose Profile |
| NCT03267576 (15) [back to overview] | Change From Baseline in Mean 24-hour Glucose Profile |
| NCT04252287 (5) [back to overview] | Change From Baseline in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 12 |
| NCT04252287 (5) [back to overview] | Change From Baseline in KCCQ Clinical Summary Score at Week 12 |
| NCT04252287 (5) [back to overview] | Change From Baseline in KCCQ Overall Summary Score at Week 12 |
| NCT04252287 (5) [back to overview] | Change From Baseline in Total Daily Step Count at Week 12 |
| NCT04252287 (5) [back to overview] | Change From Baseline in KCCQ Individual Domain Scores (Physical Limitation and Quality of Life) at Week 12 |
| NCT04288778 (4) [back to overview] | Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 |
| NCT04288778 (4) [back to overview] | Percentage of Participants With Unexpected Adverse Events (AEs) |
| NCT04288778 (4) [back to overview] | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) |
| NCT04288778 (4) [back to overview] | Percentage of Participants With Adverse Drug Reactions (ADRs) |
Percent Change in Body Weight From Baseline to Week 12
The table below shows the mean percent change in body weight from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change. (NCT00642278)
Timeframe: Day 1 (Baseline) and Week 12
| Intervention | Percent change (Mean) |
|---|
| Placebo | -1.1 |
| Canagliflozin 50 mg Daily | -2.3 |
| Canagliflozin 100 mg Daily | -2.6 |
| Canagliflozin 200 mg Daily | -2.7 |
| Canagliflozin 300 mg Daily | -3.4 |
| Canagliflozin 300 mg Twice Daily | -3.4 |
| Sitagliptin 100 mg Daily | -0.6 |
Absolute Change in Body Weight From Baseline to Week 12
The table below shows the mean absolute change in body weight from Baseline to Week 12 for each treatment group. (NCT00642278)
Timeframe: Day 1 (Baseline) and Week 12
| Intervention | kg (Mean) |
|---|
| Placebo | -0.78 |
| Canagliflozin 50 mg Daily | -1.96 |
| Canagliflozin 100 mg Daily | -2.25 |
| Canagliflozin 200 mg Daily | -2.32 |
| Canagliflozin 300 mg Daily | -2.88 |
| Canagliflozin 300 mg Twice Daily | -2.87 |
| Sitagliptin 100 mg Daily | -0.43 |
Change in Overnight Urine Glucose/Creatinine Ratio From Baseline to Week 12
The table below shows the mean change in overnight urine glucose/creatinine ratio from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change. (NCT00642278)
Timeframe: Day 1 (Baseline) and Week 12
| Intervention | mg/mg (Mean) |
|---|
| Placebo | 1.9 |
| Canagliflozin 50 mg Daily | 35.4 |
| Canagliflozin 100 mg Daily | 51.5 |
| Canagliflozin 200 mg Daily | 50.5 |
| Canagliflozin 300 mg Daily | 49.4 |
| Canagliflozin 300 mg Twice Daily | 61.6 |
| Sitagliptin 100 mg Daily | -1.9 |
Change in HbA1c From Baseline to Week 12
The table below shows the mean change in HbA1c from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change. (NCT00642278)
Timeframe: Day 1 (Baseline) and Week 12
| Intervention | Percent (Mean) |
|---|
| Placebo | -0.22 |
| Canagliflozin 50 mg Daily | -0.79 |
| Canagliflozin 100 mg Daily | -0.76 |
| Canagliflozin 200 mg Daily | -0.70 |
| Canagliflozin 300 mg Daily | -0.92 |
| Canagliflozin 300 mg Twice Daily | -0.95 |
| Sitagliptin 100 mg Daily | -0.74 |
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 12
The table below shows the mean change in FPG from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change. (NCT00642278)
Timeframe: Day 1 (Baseline) and Week 12
| Intervention | mmol/L (Mean) |
|---|
| Placebo | 0.2 |
| Canagliflozin 50 mg Daily | -0.9 |
| Canagliflozin 100 mg Daily | -1.4 |
| Canagliflozin 200 mg Daily | -1.5 |
| Canagliflozin 300 mg Daily | -1.4 |
| Canagliflozin 300 mg Twice Daily | -1.3 |
| Sitagliptin 100 mg Daily | -0.7 |
Percentage of Patients With Symptoms of Hypoglycemia
The table below shows the percentage of patients who experienced symptomatic hypoglycemic events between Baseline and Week 12. (NCT00642278)
Timeframe: Up to Week 12
| Intervention | Percentage of patients (Number) |
|---|
| Placebo | 2 |
| Canagliflozin 50 mg Daily | 0 |
| Canagliflozin 100 mg Daily | 2 |
| Canagliflozin 200 mg Daily | 6 |
| Canagliflozin 300 mg Daily | 0 |
| Canagliflozin 300 mg Twice Daily | 3 |
| Sitagliptin 100 mg Daily | 5 |
Change in Waist Circumference From Baseline to Week 12
The table below shows the mean change in waist circumference from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the least-squares mean change. (NCT00650806)
Timeframe: Day 1 (Baseline) and Week 12
| Intervention | cm (Mean) |
|---|
| Placebo | -1.2 |
| Canagliflozin 50 mg | -1.4 |
| Canagliflozin 100 mg | -2.9 |
| Canagliflozin 300 mg | -2.6 |
Change in Hip Circumference From Baseline to Week 12
The table below shows the mean change in hip circumference from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the least-squares mean change. (NCT00650806)
Timeframe: Day 1 (Baseline) and Week 12
| Intervention | cm (Mean) |
|---|
| Placebo | 0.1 |
| Canaglifozin 50 mg | -2.0 |
| Canagliflozin 100 mg | -2.1 |
| Canagliflozin 300 mg | -3.0 |
Change in Body Mass Index (BMI) From Baseline to Week 12
The table below shows the mean change in BMI from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the least-squares mean change. (NCT00650806)
Timeframe: Day 1 (Baseline) and Week 12
| Intervention | kg/m2 (Mean) |
|---|
| Placebo | -0.4 |
| Canagliflozin 50 mg | -0.7 |
| Canagliflozin 100 mg | -1.0 |
| Canagliflozin 300 mg | -0.9 |
Absolute Change in Body Weight From Baseline to Week 12
The table below shows the mean absolute change in body weight from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the least-squares mean change. (NCT00650806)
Timeframe: Day 1 (Baseline) and Week 12
| Intervention | kg (Mean) |
|---|
| Placebo | -1.1 |
| Canagliflozin 50 mg | -1.9 |
| Canagliflozin 100 mg | -2.8 |
| Canagliflozin 300 mg | -2.4 |
Percentage of Patients Who Lost at Least 5% of Their Initial Body Weight by Week 12
The table below shows the percentage of patients who lost at least 5% of their initial body weight by Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo). (NCT00650806)
Timeframe: Day 1 (Baseline) and Week 12
| Intervention | Percentage of patients (Number) |
|---|
| Placebo | 8.1 |
| Canagliflozin 50 mg | 12.6 |
| Canagliflozin 100 mg | 18.8 |
| Canagliflozin 300 mg | 17.2 |
Percentage of Patients Who Lost at Least 10% of Their Initial Body Weight by Week 12
The table below shows the percentage of patients who lost at least 10% of their initial body weight by Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo). (NCT00650806)
Timeframe: Day 1 (Baseline) and Week 12
| Intervention | Percentage of patients (Number) |
|---|
| Placebo | 0.0 |
| Canagliflozin 50 mg | 3.2 |
| Canagliflozin 100 mg | 2.4 |
| Canagliflozin 300 mg | 1.1 |
Percent Change in Body Weight From Baseline to Week 12
The table below shows the mean percent change in body weight from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the least-squares mean percent change. (NCT00650806)
Timeframe: Day 1 (Baseline) and Week 12
| Intervention | Percent change (Mean) |
|---|
| Placebo | -1.1 |
| Canagliflozin 50 mg | -2.0 |
| Canagliflozin 100 mg | -2.8 |
| Canaglifloziin 300 mg | -2.5 |
Change in Waist/Hip Ratio From Baseline to Week 12
The table below shows the mean change in waist/hip ratio from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the least-squares mean change. (NCT00650806)
Timeframe: Day 1 (Baseline) and Week 12
| Intervention | ratio (Mean) |
|---|
| Placebo | -0.011 |
| Canaglifozin 50 mg | 0.003 |
| Canagliflozin 100 mg | -0.008 |
| Canagliflozin 300 mg | -0.004 |
Change in HbA1c From Baseline to Week 104
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 104 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in the LS mean change. (NCT00968812)
Timeframe: Baseline, Week 104
| Intervention | Percent (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | -0.65 |
| Canagliflozin 300 mg | -0.74 |
| Glimepiride | -0.55 |
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 treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in the LS mean change. (NCT00968812)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | Percent (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | -0.82 |
| Canagliflozin 300 mg | -0.93 |
| Glimepiride | -0.81 |
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 treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in the LS mean percent change. (NCT00968812)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | Percent change (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | -4.2 |
| Canagliflozin 300 mg | -4.7 |
| Glimepiride | 1.0 |
Percentage of Patients Experiencing at Least 1 Hypoglycemic Event From Baseline to Week 52
The table below shows the percentage of patients who experienced at least 1 documented hypoglycemic event from Baseline to Week 52 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in percentages. (NCT00968812)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | Percentage of patients (Number) |
|---|
| Canagliflozin 100 mg | 5.6 |
| Canagliflozin 300 mg | 4.9 |
| Glimepiride | 34.2 |
Change From Baseline in Homeostasis Model Assessment 2 Steady-State Beta-Cell Function (HOMA2-%B) at the End-of-Treatment (EOT)
The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-cell function. HOMA2-%B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady-state beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100 percent. (NCT01032629)
Timeframe: Baseline and end of treatment (approximately 338 weeks)
| Intervention | Percentage of HOMA2 (Least Squares Mean) |
|---|
| Placebo | 4.02 |
| Canagliflozin 100 mg | 6.82 |
| Canagliflozin 300 mg | 8.09 |
Change From Baseline in Glycated Hemoglobin (HbA1c) at End-of-Treatment
Change from baseline in glycated hemoglobin (HbA1c) percentage (%) was assessed at end of treatment. Glycated hemoglobin is a form of hemoglobin that is measured primarily to identify the average glucose concentration in the blood. (NCT01032629)
Timeframe: Baseline and end of treatment (approximately 338 weeks)
| Intervention | HbA1c (%) (Least Squares Mean) |
|---|
| Placebo | 0.01 |
| Canagliflozin 100 mg | -0.26 |
| Canagliflozin 300 mg | -0.31 |
Change From Baseline in Fasting Plasma Glucose (FPG) Levels at End-of-Treatment
Change from baseline in the fasting plasma glucose levels at end-of-treatment was assessed. (NCT01032629)
Timeframe: Baseline and end of treatment (approximately 338 weeks)
| Intervention | Millimoles per liter (mmol/L) (Least Squares Mean) |
|---|
| Placebo | 0.16 |
| Canagliflozin 100 mg | -0.42 |
| Canagliflozin 300 mg | -0.57 |
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at End-of-Treatment
Change from baseline in Estimated Glomerular Filtration Rate (eGFR) was assessed at end of treatment. GFR is a measure of the rate at which blood is filtered by the kidney. Modification of Diet in Renal Disease (MDRD) is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine, age, race, and sex. eGFR milliliters/minute/1.73 meters square (mL/min/1.73 m^2) = 175 * (serum creatinine) ^ 1.154 * (Age) ^-0.203 *(0.742 if female) * (1.21 if Black). (NCT01032629)
Timeframe: Baseline and end of treatment (approximately 338 weeks)
| Intervention | mL/min/1.73 m^2 (Least Squares Mean) |
|---|
| Placebo | -5.23 |
| Canagliflozin 100 mg | -3.55 |
| Canagliflozin 300 mg | -3.98 |
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at End-of-Treatment
Change from baseline in systolic blood pressure and diastolic blood pressure was assessed. (NCT01032629)
Timeframe: Baseline and end of treatment (approximately 338 weeks)
,,
| Intervention | Millimeter of mercury (mmHg) (Least Squares Mean) |
|---|
| SBP(Change at end of treatment) | DBP (Change at end of treatment) |
|---|
| Canagliflozin 100 mg | -4.91 | -3.70 |
| Canagliflozin 300 mg | -6.49 | -4.51 |
| Placebo | -1.96 | -2.88 |
Change From Baseline in Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) Levels at End-of-Treatment
Change from baseline in cholesterol, high-density lipoprotein cholesterol and low density lipoprotein cholesterol levels were assessed. (NCT01032629)
Timeframe: Baseline and end of treatment (approximately 338 weeks)
,,
| Intervention | mmol/L (Least Squares Mean) |
|---|
| Cholesterol (change at EOT) | HDL-C (change at EOT) | LDL-C (change at EOT) |
|---|
| Canagliflozin 100 mg | 0.11 | 0.04 | 0.04 |
| Canagliflozin 300 mg | 0.16 | 0.05 | 0.10 |
| Placebo | -0.07 | -0.01 | -0.07 |
Percentage of Participants With Progression of Albuminuria at the End-of-Treatment
Progression defined as the development of micro-albuminuria (albumin/creatinine ratio (ACR) greater than or equal to [>=] 30 milligram per gram (mg/g) and less than or equal to <= 300 mg/g) or macroalbuminuria (ACR of >300 mg/g) in a participant with baseline normoalbuminuria or the development of macro-albuminuria in a participant with baseline microalbuminuria. Percentage of participants with progression of albuminuria at the end-of-treatment were assessed. (NCT01032629)
Timeframe: End of treatment (approximately 338 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Placebo | 24.0 |
| Canagliflozin 100 mg | 20.2 |
| Canagliflozin 300 mg | 18.3 |
Percent Change From Baseline in Body Weight at End-of-Treatment
Percent change from baseline in body weight was assessed at the end of treatment. (NCT01032629)
Timeframe: Baseline and end of treatment (approximately 338 weeks)
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | -0.50 |
| Canagliflozin 100 mg | -3.47 |
| Canagliflozin 300 mg | -4.12 |
Major Adverse Cardiovascular Events (MACE) Composite of Cardiovascular (CV) Death, Non-Fatal Myocardial Infarction (MI), and Non-Fatal Stroke
MACE, defined as a composite of CV death, non-fatal MI, and nonfatal stroke. Adjudication of these events by the Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of MACE are presented. (NCT01032629)
Timeframe: Up to approximately 8 years
| Intervention | Events per 1000 patient-year (Number) |
|---|
| Placebo | 30.36 |
| Canagliflozin 100 mg | 28.41 |
| Canagliflozin 300 mg | 25.37 |
| Canagliflozin (Total) | 26.89 |
Change From Baseline in Urinary Albumin/Creatinine Ratio at End-of-Treatment
Urinary Albumin/Creatinine Ratio is a potential marker of chronic kidney disease, calculated as a ratio of Urinary Albumin and Urinary Creatinine. (NCT01032629)
Timeframe: Baseline and End of treatment (approximately 338 weeks)
| Intervention | Milligram per gram (mg/g) (Geometric Mean) |
|---|
| Placebo | 29.30 |
| Canagliflozin 100 mg | 25.50 |
| Canagliflozin 300 mg | 24.47 |
Change From Baseline in Triglycerides Levels at End-of-Treatment
Change from baseline in triglycerides levels was assessed. (NCT01032629)
Timeframe: Baseline and end of treatment (approximately 338 weeks)
| Intervention | mmol/L (Mean) |
|---|
| Placebo | 0.05 |
| Canagliflozin 100 mg | 0.13 |
| Canagliflozin 300 mg | 0.09 |
Change From Baseline in Proinsulin/Insulin (PI/I) Ratio at the End-of-Treatment
A raised proinsulin-to-insulin ratio due to impaired processing of proinsulin is an early marker of beta cell dysfunction. Beta-cell dysfunction was evaluated by calculating the PI/I ratio, which estimates the capacity of beta cells to convert proinsulin to insulin and may represent an acceptable method to indicate the degree of beta-cell secretion. (NCT01032629)
Timeframe: Baseline and end of treatment (approximately 338 weeks)
| Intervention | Picomole per milli international units (Least Squares Mean) |
|---|
| Placebo | 0.70 |
| Canagliflozin 100 mg | 0.67 |
| Canagliflozin 300 mg | 1.03 |
Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) to High-Density Lipoprotein-Cholesterol (HDL-C) Ratio at End-of-Treatment
Change from baseline in LDL-C to HDL-C ratio was assessed. (NCT01032629)
Timeframe: Baseline and end of treatment (approximately 338 weeks)
| Intervention | Ratio (Least Squares Mean) |
|---|
| Placebo | -0.04 |
| Canagliflozin 100 mg | -0.02 |
| Canagliflozin 300 mg | 0.00 |
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 group minus placebo) in the LS mean change. (NCT01064414)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent (Least Squares Mean) |
|---|
| Placebo | -0.03 |
| Canagliflozin 100 mg | -0.33 |
| Canagliflozin 300 mg | -0.44 |
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 (ie, each canagliflozin group minus placebo) in the percentage. (NCT01064414)
Timeframe: Week 26
| Intervention | Percentage of patients (Number) |
|---|
| Placebo | 17.2 |
| Canagliflozin 100 mg | 27.3 |
| Canagliflozin 300 mg | 32.6 |
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 group minus placebo) in the LS mean change. (NCT01064414)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Placebo | 0.49 |
| Canagliflozin 100 mg | -14.9 |
| Canagliflozin 300 mg | -11.7 |
Change in HbA1c From Baseline to Week 26 (Main Study)
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. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent (Least Squares Mean) |
|---|
| Placebo | 0.14 |
| Canagliflozin 100 mg | -0.77 |
| Canagliflozin 300 mg | -1.03 |
Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (High Glycemic Substudy)
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 in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | -118 |
| Canagliflozin 300 mg | -126 |
Percent Change in Body Weight From Baseline to Week 26 (Main Study)
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 percent change. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | -0.6 |
| Canagliflozin 100 mg | -2.8 |
| Canagliflozin 300 mg | -3.9 |
Percent Change in Body Weight From Baseline to Week 26 (High Glycemic Substudy)
The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | -3.0 |
| Canagliflozin 300 mg | -3.8 |
Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (Main Study)
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. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mmHg (Least Squares Mean) |
|---|
| Placebo | 0.38 |
| Canagliflozin 100 mg | -3.34 |
| Canagliflozin 300 mg | -5.04 |
Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (High Glycemic Substudy)
The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mmHg (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | -4.47 |
| Canagliflozin 300 mg | -4.97 |
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (High Glycemic Substudy)
The table below shows the least-squares mean percent change in HDL-C from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | 2.4 |
| Canagliflozin 300 mg | 10.8 |
Change in HbA1c From Baseline to Week 26 (High Glycemic Substudy)
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | -2.13 |
| Canagliflozin 300 mg | -2.56 |
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (Main Study)
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. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Placebo | 8.33 |
| Canagliflozin 100 mg | -27.2 |
| Canagliflozin 300 mg | -35.0 |
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (High Glycemic Substudy)
The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | -81.7 |
| Canagliflozin 300 mg | -86.3 |
Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (Main Study)
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 group minus placebo) in the LS mean change. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Placebo | 5.19 |
| Canagliflozin 100 mg | -42.9 |
| Canagliflozin 300 mg | -58.8 |
Percentage of Patients With HbA1c <7% at Week 26 (Main Study)
The table below shows the percentage of patients with HbA1c <7% at Week 26. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage. (NCT01081834)
Timeframe: Week 26
| Intervention | Percentage of patients (Number) |
|---|
| Placebo | 20.6 |
| Canagliflozin 100 mg | 44.5 |
| Canagliflozin 300 mg | 62.4 |
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (Main Study)
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 group minus placebo) in the LS mean percent change. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | 4.4 |
| Canagliflozin 100 mg | 11.2 |
| Canagliflozin 300 mg | 10.5 |
Percent Change in Triglycerides From Baseline to Week 26 (High Glycemic Substudy)
The table below shows the least-squares mean percent change in triglycerides from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | -0.6 |
| Canagliflozin 300 mg | -12.7 |
Percent Change in Triglycerides From Baseline to Week 26 (Main Study)
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 percent change. (NCT01081834)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | 7.8 |
| Canagliflozin 100 mg | 2.5 |
| Canagliflozin 300 mg | -2.4 |
Percentage of Patients With HbA1c <7% at Week 26 (High Glycemic Substudy)
The table below shows the percentage of patients with HbA1c <7% at Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. (NCT01081834)
Timeframe: Week 26
| Intervention | Percentage of patients (Number) |
|---|
| Canagliflozin 100 mg | 17.4 |
| Canagliflozin 300 mg | 11.6 |
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 group minus placebo) in the LS mean percent change. (NCT01106625)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | 11.6 |
| Canagliflozin 100 mg | 5.4 |
| Canagliflozin 300 mg | 8.5 |
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 group minus placebo) in the LS mean percent change. (NCT01106625)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | 3.2 |
| Canagliflozin 100 mg | 5.7 |
| Canagliflozin 300 mg | 6.5 |
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 group minus placebo) in the LS mean percent change. (NCT01106625)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | -0.7 |
| Canagliflozin 100 mg | -2.1 |
| Canagliflozin 300 mg | -2.6 |
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 group minus placebo) in the LS mean change. (NCT01106625)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mmHg (Least Squares Mean) |
|---|
| Placebo | -2.65 |
| Canagliflozin 100 mg | -4.89 |
| Canagliflozin 300 mg | -4.27 |
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 (ie, each canagliflozin group minus placebo) in the percentage. (NCT01106625)
Timeframe: Week 26
| Intervention | Percentage of patients (Number) |
|---|
| Placebo | 18 |
| Canagliflozin 100 mg | 43.2 |
| Canagliflozin 300 mg | 56.6 |
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 group minus placebo) in the LS mean change. (NCT01106625)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Placebo | 4.11 |
| Canagliflozin 100 mg | -18.2 |
| Canagliflozin 300 mg | -30.5 |
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 group minus placebo) in the LS mean change. (NCT01106625)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent (Least Squares Mean) |
|---|
| Placebo | -0.13 |
| Canagliflozin 100 mg | -0.85 |
| Canagliflozin 300 mg | -1.06 |
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 group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent (Least Squares Mean) |
|---|
| Placebo | -0.03 |
| Canagliflozin 100 mg | -0.60 |
| Canagliflozin 300 mg | -0.73 |
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 group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | -0.1 |
| Canagliflozin 100 mg | -2.4 |
| Canagliflozin 300 mg | -3.1 |
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 (ie, each canagliflozin group minus placebo) in the percentage. (NCT01106651)
Timeframe: Week 26
| Intervention | Percentage of patients (Number) |
|---|
| Placebo | 28.0 |
| Canagliflozin 100 mg | 47.7 |
| Canagliflozin 300 mg | 58.5 |
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
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. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | kg (Least Squares Mean) |
|---|
| Placebo | -0.28 |
| Canagliflozin 100 mg | -1.87 |
| Canagliflozin 300 mg | -2.38 |
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 group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | 7.7 |
| Canagliflozin 100 mg | 2.8 |
| Canagliflozin 300 mg | 8.4 |
Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26
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. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | -0.5 |
| Canagliflozin 100 mg | -0.9 |
| Canagliflozin 300 mg | -1.0 |
Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26
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. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | 0.5 |
| Canagliflozin 100 mg | 0.7 |
| Canagliflozin 300 mg | 0.2 |
Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26
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. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | -1.0 |
| Canagliflozin 100 mg | -0.7 |
| Canagliflozin 300 mg | -0.6 |
Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26
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. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | -0.5 |
| Canagliflozin 100 mg | -0.7 |
| Canagliflozin 300 mg | -0.8 |
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 group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Placebo | 7.39 |
| Canagliflozin 100 mg | -18.1 |
| Canagliflozin 300 mg | -20.3 |
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 or each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | 1.5 |
| Canagliflozin 100 mg | 6.8 |
| Canagliflozin 300 mg | 6.2 |
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
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. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent (Least Squares Mean) |
|---|
| Placebo | 0.02 |
| Canagliflozin 100 mg | -1.04 |
| Canagliflozin 300 mg | -1.18 |
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 group minus placebo) in the LS mean change. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mmHg (Least Squares Mean) |
|---|
| Placebo | 1.10 |
| Canagliflozin 100 mg | -3.52 |
| Canagliflozin 300 mg | -6.79 |
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
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. (NCT01106651)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent (Least Squares Mean) |
|---|
| Placebo | 0.00 |
| Canagliflozin 100 mg | -1.03 |
| Canagliflozin 300 mg | -1.18 |
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. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Placebo/Sitagliptin | -9.79 |
| Canagliflozin 100 mg | -47.9 |
| Canagliflozin 300 mg | -57.1 |
| Sitagliptin 100 mg | -49.3 |
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. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo/Sitagliptin | 3.7 |
| Canagliflozin 100 mg | 10.4 |
| Canagliflozin 300 mg | 12.1 |
| Sitagliptin 100 mg | 5.0 |
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. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | Percent change (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | 11.2 |
| Canagliflozin 300 mg | 13.3 |
| Sitagliptin 100 mg | 6.0 |
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. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo/Sitagliptin | 3.2 |
| Canagliflozin 100 mg | 1.6 |
| Canagliflozin 300 mg | -1.4 |
| Sitagliptin 100 mg | 1.0 |
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. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | mmHg (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | -3.53 |
| Canagliflozin 300 mg | -4.65 |
| Sitagliptin 100 mg | -0.66 |
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. (NCT01106677)
Timeframe: Week 26
| Intervention | Percentage of patients (Number) |
|---|
| Placebo/Sitagliptin | 29.8 |
| Canagliflozin 100 mg | 45.5 |
| Canagliflozin 300 mg | 57.8 |
| Sitagliptin 100 mg | 54.5 |
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. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | Percent (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | -0.73 |
| Canagliflozin 300 mg | -0.88 |
| Sitagliptin 100 mg | -0.73 |
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. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo/Sitagliptin | -1.2 |
| Canagliflozin 100 mg | -3.7 |
| Canagliflozin 300 mg | -4.2 |
| Sitagliptin 100 mg | -1.2 |
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. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | Percent change (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | -3.8 |
| Canagliflozin 300 mg | -4.2 |
| Sitagliptin 100 mg | -1.3 |
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. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mmHg (Least Squares Mean) |
|---|
| Placebo/Sitagliptin | 1.52 |
| Canagliflozin 100 mg | -3.84 |
| Canagliflozin 300 mg | -5.06 |
| Sitagliptin 100 mg | -1.83 |
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. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent (Least Squares Mean) |
|---|
| Placebo/Sitagliptin | -0.17 |
| Canagliflozin 100 mg | -0.79 |
| Canagliflozin 300 mg | -0.94 |
| Sitagliptin 100 mg | -0.82 |
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. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | -26.2 |
| Canagliflozin 300 mg | -35.2 |
| Sitagliptin 100 mg | -17.7 |
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. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Placebo/Sitagliptin | 2.47 |
| Canagliflozin 100 mg | -27.3 |
| Canagliflozin 300 mg | -37.8 |
| Sitagliptin 100 mg | -20.2 |
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. (NCT01106677)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | Percent change (Least Squares Mean) |
|---|
| Canagliflozin 100 mg | 1.9 |
| Canagliflozin 300 mg | 2.7 |
| Sitagliptin 100 mg | -0.4 |
Change in Homeostasis Model Assessment (HOMA2-%B) From Baseline to Week 26
HOMA2-%B is a measure of beta cell function (the cells in the pancreas that produce and store insulin). The table below shows the least-squares (LS) mean change in HOMA2-%B 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. (NCT01106690)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | HOMA2-%B (Least Squares Mean) |
|---|
| Placebo/Sitagliptin | 0.91 |
| Canagliflozin 100 mg | 15.19 |
| Canagliflozin 300 mg | 18.14 |
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 group minus placebo) in the LS mean change. (NCT01106690)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent (Least Squares Mean) |
|---|
| Placebo/Sitagliptin | -0.26 |
| Canagliflozin 100 mg | -0.89 |
| Canagliflozin 300 mg | -1.03 |
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 group minus placebo) in the LS mean change. (NCT01106690)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Placebo/Sitagliptin | 2.54 |
| Canagliflozin 100 mg | -26.8 |
| Canagliflozin 300 mg | -33.2 |
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 group minus placebo) in the LS mean change. (NCT01106690)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | mmHg (Least Squares Mean) |
|---|
| Placebo/Sitagliptin | -1.24 |
| Canagliflozin 100 mg | -5.30 |
| Canagliflozin 300 mg | -4.70 |
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 (ie, each canagliflozin group minus placebo) in the percentage. (NCT01106690)
Timeframe: Week 26
| Intervention | Percentage of patients (Number) |
|---|
| Placebo/Sitagliptin | 32.5 |
| Canagliflozin 100 mg | 46.9 |
| Canagliflozin 300 mg | 64.3 |
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 group minus placebo) in the LS mean percent change. (NCT01106690)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo/Sitagliptin | 15.2 |
| Canagliflozin 100 mg | 3.2 |
| Canagliflozin 300 mg | -1.7 |
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 group minus placebo) in the LS mean percent change. (NCT01106690)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo/Sitagliptin | 2.4 |
| Canagliflozin 100 mg | 7.2 |
| Canagliflozin 300 mg | 8.9 |
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 group minus placebo) in the LS mean percent change. (NCT01106690)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo/Sitagliptin | -0.1 |
| Canagliflozin 100 mg | -2.8 |
| Canagliflozin 300 mg | -3.8 |
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52
The table below shows the mean percent change in HDL-C from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. (NCT01137812)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | Percent change (Least Squares Mean) |
|---|
| Canagliflozin 300 mg | 7.6 |
| Sitagliptin 100 mg | 0.6 |
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 treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean percent change. (NCT01137812)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | Percent change (Least Squares Mean) |
|---|
| Canagliflozin 300 mg | -2.5 |
| Sitagliptin 100 mg | 0.3 |
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 treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. (NCT01137812)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | mmHg (Least Squares Mean) |
|---|
| Canagliflozin 300 mg | -5.06 |
| Sitagliptin 100 mg | 0.85 |
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 treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. (NCT01137812)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | Percent (Least Squares Mean) |
|---|
| Canagliflozin 300 mg | -1.03 |
| Sitagliptin 100 mg | -0.66 |
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 treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. (NCT01137812)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Canagliflozin 300 mg | -29.9 |
| Sitagliptin 100 mg | -5.85 |
Percentage of Patients With HbA1c <7% at Week 52
The table below shows the percentage of patients with HbA1c <7% at Week 52 in each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the percentage. (NCT01137812)
Timeframe: Week 52
| Intervention | Percentage of patients (Number) |
|---|
| Canagliflozin 300 mg | 47.6 |
| Sitagliptin 100 mg | 35.3 |
Percent Change in Triglycerides From Baseline to Week 52
The table below shows the mean percent change in triglycerides from Baseline to Week 52 for each treatment group. The statistical analysis shows the treatment difference (ie, between canagliflozin and sitagliptin) in the LS mean change. (NCT01137812)
Timeframe: Day 1 (Baseline) and Week 52
| Intervention | Percent change (Least Squares Mean) |
|---|
| Canagliflozin 300 mg | 9.6 |
| Sitagliptin 100 mg | 11.9 |
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18
The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01340664)
Timeframe: Day 1 (Baseline) and Week 18
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Placebo | 8.1 |
| Canagliflozin 50 mg Bid | -15.5 |
| Canagliflozin 150 mg Bid | -15.9 |
Percentage of Patients With HbA1c <7% at Week 18
The table below shows the percentage of patients with HbA1c <7% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage. (NCT01340664)
Timeframe: Week 18
| Intervention | Percentage of Participants (Number) |
|---|
| Placebo | 31.5 |
| Canagliflozin 50 mg Bid | 47.8 |
| Canagliflozin 150 mg Bid | 57.1 |
Change in HbA1c From Baseline to Week 18
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01340664)
Timeframe: Day 1 (Baseline) and Week 18
| Intervention | Percent (Least Squares Mean) |
|---|
| Placebo | -0.01 |
| Canagliflozin 50 mg Bid | -0.45 |
| Canagliflozin 150 mg Bid | -0.61 |
Percent Change in Body Weight From Baseline to Week 18
The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change. (NCT01340664)
Timeframe: Day 1 (Baseline) and Week 18
| Intervention | Percent change (Least Squares Mean) |
|---|
| Placebo | -0.6 |
| Canagliflozin 50 mg Bid | -2.8 |
| Canagliflozin 150 mg Bid | -3.2 |
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18
The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01381900)
Timeframe: Day 1 (Baseline) and Week 18
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Placebo | -0.40 |
| Canagliflozin 100 mg | -1.44 |
| Canagliflozin 300 mg | -1.83 |
Change in Glycosylated Hemoglobin (HbA1c) From Baseline to Week 18
The table below shows the least-squares (LS) mean change in HbA1c from baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. (NCT01381900)
Timeframe: Day 1 (Baseline) and Week 18
| Intervention | Percent (Least Squares Mean) |
|---|
| Placebo | -0.47 |
| Canagliflozin 100 mg | -0.97 |
| Canagliflozin 300 mg | -1.06 |
Percent Change in Body Weight From Baseline to Week 18
The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change. (NCT01381900)
Timeframe: Day 1 (Baseline) and Week 18
| Intervention | Pecent change (Least Squares Mean) |
|---|
| Placebo | -0.8 |
| Canagliflozin 100 mg | -2.9 |
| Canagliflozin 300 mg | -3.1 |
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <7% at Week 18
The table below shows the percentage of patients with HbA1c <7% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage. (NCT01381900)
Timeframe: Day 1 (Baseline) and Week 18
| Intervention | Percentage of patients (Number) |
|---|
| Placebo | 27.8 |
| Canagliflozin 100 mg | 49.1 |
| Canagliflozin 300 mg | 52.9 |
Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <6.5% at Week 18
The table below shows the percentage of patients with HbA1c <6.5% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage. (NCT01381900)
Timeframe: Day 1 (Baseline) and Week 18
| Intervention | Percentage of patients (Number) |
|---|
| Placebo | 11.7 |
| Canagliflozin 100 mg | 21.6 |
| Canagliflozin 300 mg | 25.3 |
Change in Systolic Blood Pressure From Baseline at Week 26
The change in systolic blood pressure from baseline at Week 26 was compared between the different treatment groups. (NCT01809327)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | millimeter of mercury (mm Hg) (Least Squares Mean) |
|---|
| Metformin XR | -0.33 |
| Canagliflozin 100 Milligram (mg) | -2.24 |
| Canagliflozin 300 mg | -2.36 |
| Canagliflozin 100 mg + Metformin XR | -2.24 |
| Canagliflozin 300 mg + Metformin XR | -1.65 |
Number of Participants With Treatment Emergent Adverse Events (AEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to 30 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. (NCT01809327)
Timeframe: Up to 30 weeks of last study drug administration
| Intervention | participants (Number) |
|---|
| Metformin XR | 89 |
| Canagliflozin 100 Milligram (mg) | 88 |
| Canagliflozin 300 mg | 95 |
| Canagliflozin 100 mg + Metformin XR | 99 |
| Canagliflozin 300 mg + Metformin XR | 105 |
Percent Change in Body Weight From Baseline to Week 26
The percentage change in body weight from baseline to Week 26 was compared between the different treatment groups. (NCT01809327)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | percent change (Least Squares Mean) |
|---|
| Metformin XR | -2.1 |
| Canagliflozin 100 Milligram (mg) | -3.0 |
| Canagliflozin 300 mg | -3.9 |
| Canagliflozin 100 mg + Metformin XR | -3.5 |
| Canagliflozin 300 mg + Metformin XR | -4.2 |
Percent Change in Fasting High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
The percentage change in Fasting High-Density Lipoprotein Cholesterol (HDL-C) from baseline to Week 26 was compared between the different treatment groups. (NCT01809327)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | percent change (Least Squares Mean) |
|---|
| Metformin XR | 10.2 |
| Canagliflozin 100 Milligram (mg) | 17.6 |
| Canagliflozin 300 mg | 16.6 |
| Canagliflozin 100 mg + Metformin XR | 15.5 |
| Canagliflozin 300 mg + Metformin XR | 14.5 |
Percent Change in Triglycerides From Baseline to Week 26
The percentage change in triglycerides from baseline to Week 26 was compared between the different treatment groups. (NCT01809327)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | percent change (Mean) |
|---|
| Metformin XR | 13.6 |
| Canagliflozin 100 Milligram (mg) | 1.7 |
| Canagliflozin 300 mg | 2.8 |
| Canagliflozin 100 mg + Metformin XR | 13.0 |
| Canagliflozin 300 mg + Metformin XR | 21.2 |
Percentage of Participants With Glycated Hemoglobin (HbAIc) Less Than 7 Percent at Week 26
The percentage of participants achieved HbAIc less than 7 percent at Week 26 was compared between the different treatment groups. (NCT01809327)
Timeframe: Week 26
| Intervention | percentage of participants (Number) |
|---|
| Metformin XR | 43.0 |
| Canagliflozin 100 Milligram (mg) | 38.8 |
| Canagliflozin 300 mg | 42.8 |
| Canagliflozin 100 mg + Metformin XR | 49.6 |
| Canagliflozin 300 mg + Metformin XR | 56.8 |
Change in Glycated Hemoglobin (HbA1c) From Baseline at Week 26
The change in the value of glycated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) from baseline at Week 26 was compared between the different treatment groups. (NCT01809327)
Timeframe: Day 1 (Baseline) and Week 26
| Intervention | percentage of hemoglobin (Least Squares Mean) |
|---|
| Metformin XR | -1.30 |
| Canagliflozin 100 Milligram (mg) | -1.37 |
| Canagliflozin 300 mg | -1.42 |
| Canagliflozin 100 mg + Metformin XR | -1.77 |
| Canagliflozin 300 mg + Metformin XR | -1.78 |
Change From Baseline in Standing Heart Rate (HR) to Day 2, to Week 3, and to Week 6
The standing heart rate was evaluated. (NCT01939496)
Timeframe: Baseline, Day 2, Week 3 and 6
,,
| Intervention | beats per minute (Mean) |
|---|
| Baseline (n=56,57,56) | Change From Baseline at Day 2 (n=55,57,56) | Change From Baseline at Week 3 (n=55,57,56) | Change From Baseline at Week 6 (n=55,57,56) |
|---|
| Canagliflozin 100 Milligram (mg) | 78.65 | 4.32 | 3.47 | 1.44 |
| Canagliflozin 300 mg | 81.86 | 2.79 | 0.48 | -0.68 |
| Placebo | 82.54 | 0.27 | -0.89 | -0.07 |
Change From Baseline in Standing Office Blood Pressure (BP) to Day 2, to Week 3, and to Week 6
The standing office blood pressure (BP) was evaluated for all participants based on the 24-hour BP recordings. SBP=Systolic Blood Pressure and DBP=Diastolic Blood Pressure. (NCT01939496)
Timeframe: Baseline, Day 2, Week 3 and 6
,,
| Intervention | millimeter of mercury (mmHg) (Mean) |
|---|
| SBP: Baseline (n=56,57,56) | SBP: Change From Baseline at Day 2 (n=55,57,56) | SBP: Change From Baseline at Week 3 (n=55,57,56) | SBP: Change From Baseline at Week 6 (n=55,57,56) | DBP: Baseline (n=55,57,56) | DBP: Change From Baseline at Day 2 (n=55,57,56) | DBP: Change From Baseline at Week 3 (n=55,57,56) | DBP: Change From Baseline at Week 6 (n=55,57,56) |
|---|
| Canagliflozin 100 Milligram (mg) | 139.3 | -2.46 | -7.12 | -7.95 | 85.25 | -0.60 | -3.47 | -2.51 |
| Canagliflozin 300 mg | 140.8 | -5.91 | -11.9 | -11.3 | 86.09 | -1.32 | -5.36 | -4.55 |
| Placebo | 140.3 | -4.36 | -6.55 | -3.76 | 85.79 | -0.65 | -2.91 | -0.89 |
Change From Baseline in the Difference in Seated Heart Rate (HR) and Standing HR to Day 2, to Week 3, and to Week 6
The difference in seated heart rate and standing heart rate was evaluated. (NCT01939496)
Timeframe: Baseline, Day 2, Week 3 and 6
,,
| Intervention | beats per minute (Mean) |
|---|
| Baseline (n=56,57,56) | Change From Baseline at Day 2 (n=55,57,56) | Change From Baseline at Week 3 (n=55,57,56) | Change From Baseline at Week 6 (n=55,57,56) |
|---|
| Canagliflozin 100 Milligram (mg) | 3.60 | 1.26 | 1.77 | 0.37 |
| Canagliflozin 300 mg | 3.73 | 1.11 | 1.38 | 0.48 |
| Placebo | 2.96 | 1.67 | 1.35 | 2.16 |
Change From Baseline in the Difference in Seated Office Blood Pressure (BP) and Standing Office BP to Day 2, to Week 3, and to Week 6
The difference in seated office blood pressure and standing office blood pressure was evaluated. (NCT01939496)
Timeframe: Baseline, Day 2, Week 3 and 6
,,
| Intervention | millimeter of mercury (mmHg) (Mean) |
|---|
| Baseline (n=56,57,56) | Change From Baseline at Day 2 (n=55,57,56) | Change From Baseline at Week 3 (n=55,57,56) | Change From Baseline at Week 6 (n=55,57,56) |
|---|
| Canagliflozin 100 Milligram (mg) | 0.78 | -0.39 | 0.40 | -2.96 |
| Canagliflozin 300 mg | 1.55 | -0.80 | -1.27 | -3.90 |
| Placebo | 2.65 | -1.13 | -0.60 | -0.41 |
Change From Baseline in the Mean 24-Hour Diastolic Blood Pressure (DBP) to Day 2 and to Week 6
The blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings. (NCT01939496)
Timeframe: Baseline, Day 2 and Week 6
,,
| Intervention | millimeter of mercury (mmHg) (Mean) |
|---|
| Baseline (n=56,57,56) | Change From Baseline at Day 2 (n=50,50,50) | Change From Baseline at Week 6 (n=54,54,55) |
|---|
| Canagliflozin 100 Milligram (mg) | 78.01 | -0.85 | -2.18 |
| Canagliflozin 300 mg | 79.31 | -0.45 | -3.27 |
| Placebo | 78.36 | 1.01 | -0.26 |
Change From Baseline in the Mean 24-Hour Systolic Blood Pressure (SBP) to Week 6
The blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings. (NCT01939496)
Timeframe: Baseline and Week 6
,,
| Intervention | millimeter of mercury (mmHg) (Mean) |
|---|
| Baseline (n=56,57,56) | Change From Baseline at Week 6 (n=54,54,55) |
|---|
| Canagliflozin 100 Milligram (mg) | 136.5 | -4.78 |
| Canagliflozin 300 mg | 139.6 | -7.31 |
| Placebo | 136.7 | -1.26 |
Change From Baseline in Mean Nighttime Systolic Blood Pressure (SBP) to Day 2 and to Week 6
The nocturnal fall (nighttime) in blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings. (NCT01939496)
Timeframe: Baseline, Day 2 and Week 6
,,
| Intervention | millimeter of mercury (mmHg) (Mean) |
|---|
| Baseline (n=56,57,56) | Change From Baseline at Day 2 (n=50,50,50) | Change From Baseline at Week 6 (n=54,54,55) |
|---|
| Canagliflozin 100 Milligram (mg) | 128.3 | -1.02 | -4.33 |
| Canagliflozin 300 mg | 130.2 | -4.37 | -6.98 |
| Placebo | 129.3 | -0.19 | -3.49 |
Change From Baseline in Seated Heart Rate (HR) to Day 2, to Week 3, and to Week 6
The seated heart rate was evaluated. (NCT01939496)
Timeframe: Baseline, Day 2, Week 3 and 6
,,
| Intervention | beats per minute (Mean) |
|---|
| Baseline (n=56,57,56) | Change From Baseline at Day 2 (n=55,57,56) | Change From Baseline at Week 3 (n=55,57,56) | Change From Baseline at Week 6 (n=55,57,56) |
|---|
| Canagliflozin 100 Milligram (mg) | 75.05 | 3.05 | 1.70 | 1.07 |
| Canagliflozin 300 mg | 78.13 | 1.68 | -0.89 | -1.16 |
| Placebo | 79.57 | -1.40 | -2.24 | -2.24 |
Change From Baseline in Seated Office Blood Pressure (BP) to Day 2, to Week 3, and to Week 6
The seated office blood pressure (BP) was evaluated for all participants based on the 24-hour BP recordings. SBP=Systolic Blood Pressure and DBP=Diastolic Blood Pressure. (NCT01939496)
Timeframe: Baseline, Day 2, Week 3 and 6
,,
| Intervention | millimeter of mercury (mmHg) (Mean) |
|---|
| SBP: Baseline (n=56,57,56) | SBP: Change From Baseline at Day 2 (n=55,57,56) | SBP: Change From Baseline at Week 3 (n=55,57,56) | SBP: Change From Baseline at Week 6 (n=55,57,56) | DBP: Baseline (n=55,57,56) | DBP: Change From Baseline at Day 2 (n=55,57,56) | DBP: Change From Baseline at Week 3 (n=55,57,56) | DBP: Change From Baseline at Week 6 (n=55,57,56) |
|---|
| Canagliflozin 100 Milligram (mg) | 138.5 | -2.06 | -7.53 | -4.98 | 82.37 | -0.26 | -2.22 | -1.52 |
| Canagliflozin 300 mg | 139.2 | -5.11 | -10.6 | -7.38 | 83.02 | -0.87 | -4.23 | -2.43 |
| Placebo | 137.7 | -3.24 | -5.95 | -3.36 | 82.67 | -2.61 | -2.84 | -1.78 |
Change From Baseline in Mean 24-Hour Systolic Blood Pressure (SBP) to Day 2
The blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings. (NCT01939496)
Timeframe: Baseline and Day 2
,,
| Intervention | millimeter of mercury (mmHg) (Mean) |
|---|
| Baseline (n=56,57,56) | Change From Baseline at Day 2 (n=50,50,50) |
|---|
| Canagliflozin 100 Milligram (mg) | 136.5 | -1.78 |
| Canagliflozin 300 mg | 139.6 | -1.97 |
| Placebo | 136.7 | 0.49 |
Change From Baseline in Body Weight to Week 6
Body weight was evaluated. (NCT01939496)
Timeframe: Baseline and Week 6
,,
| Intervention | Kilogram (kg) (Mean) |
|---|
| Baseline (n=56,57,56) | Change From Baseline at Week 6 (n=54,55,56) |
|---|
| Canagliflozin 100 Milligram (mg) | 95.32 | -0.98 |
| Canagliflozin 300 mg | 96.06 | -1.47 |
| Placebo | 91.65 | 0.14 |
Change From Baseline in Fasting Plasma Glucose (FPG) to Week 6
The fasting plasma glucose was evaluated. (NCT01939496)
Timeframe: Baseline and Week 6
,,
| Intervention | millimoles per liter (mmol/L) (Mean) |
|---|
| Baseline (n=56,57,56) | Change From Baseline at Week 6 (n=55,54,55) |
|---|
| Canagliflozin 100 Milligram (mg) | 9.69 | -0.03 |
| Canagliflozin 300 mg | 9.38 | -1.27 |
| Placebo | 9.84 | -0.38 |
Change From Baseline in Mean Daytime Diastolic Blood Pressure (DBP) to Day 2 and to Week 6
The diurnal rise (daytime) in blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings. (NCT01939496)
Timeframe: Baseline, Day 2 and Week 6
,,
| Intervention | millimeter of mercury (mmHg) (Mean) |
|---|
| Baseline (n=56,57,56) | Change From Baseline at Day 2 (n=50,50,50) | Change From Baseline at Week 6 (n=54,54,55) |
|---|
| Canagliflozin 100 Milligram (mg) | 80.53 | -1.08 | -2.39 |
| Canagliflozin 300 mg | 81.81 | 0.03 | -3.23 |
| Placebo | 80.84 | 1.21 | -0.20 |
Change From Baseline in Mean Daytime Systolic Blood Pressure (SBP) to Day 2 and to Week 6
The diurnal rise (daytime) in blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings. (NCT01939496)
Timeframe: Baseline, Day 2 and Week 6
,,
| Intervention | millimeter of mercury (mmHg) (Mean) |
|---|
| Baseline (n=56,57,56) | Change From Baseline at Day 2 (n=50,50,50) | Change From Baseline at Week 6 (n=54,54,55) |
|---|
| Canagliflozin 100 Milligram (mg) | 139.6 | -2.06 | -5.05 |
| Canagliflozin 300 mg | 142.8 | -1.16 | -7.36 |
| Placebo | 139.4 | 0.96 | -0.65 |
Change From Baseline in Mean Nighttime Diastolic Blood Pressure (DBP) to Day 2 and to Week 6
The nocturnal fall (nighttime) in blood pressure (BP) was evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the 24-hour BP recordings. (NCT01939496)
Timeframe: Baseline, Day 2 and Week 6
,,
| Intervention | millimeter of mercury (mmHg) (Mean) |
|---|
| Baseline (n=56,57,56) | Change From Baseline at Day 2 (n=50,50,50) | Change From Baseline at Week 6 (n=54,54,55) |
|---|
| Canagliflozin 100 Milligram (mg) | 71.10 | -0.23 | -1.73 |
| Canagliflozin 300 mg | 72.31 | -2.24 | -3.42 |
| Placebo | 71.57 | 0.87 | -0.98 |
Progression of Albuminuria
Progression defined as the development of micro-albuminuria (Urine Albumin Creatinine Ratio [UACR] 30 to 300 milligram per gram [mg/g]) or macroalbuminuria (Albumin/creatinine ratio [ACR] of greater than [>] 300 mg/g) in a participant with baseline normoalbuminuria (ACR less than [<] 30 mg/g) or the development of macro-albuminuria in a participant with baseline microalbuminuria with an ACR increase greater than or equal to (>=) 30 percent from baseline. Participants with macroalbuminuria at baseline (ACR>300 mg/g) were excluded from the analysis. Event rate was estimated based on the time to the first occurrence of the event. (NCT01989754)
Timeframe: Up to 3 years
| Intervention | Events per 1000 patient-year (Number) |
|---|
| Placebo | 153.01 |
| Canagliflozin (Experimental) | 99.80 |
Composite of Cardiovascular (CV) Death Events or Hospitalization for Heart Failure
Analyses were using adjudicated events, that is (i.e.) CV death events or hospitalization due to heart failure, and adjudication of these outcomes by the Endpoint Adjudication Committee (EAC) were done in a blinded fashion. Event rate was estimated based on the time to the first occurrence of the event. (NCT01989754)
Timeframe: Approximately 3 years
| Intervention | Events per 1000 patient-years (Number) |
|---|
| Placebo | 21.91 |
| Canagliflozin (Experimental) | 15.85 |
Cardiovascular (CV) Death
Analyses were using adjudicated events, i.e. CV death events, and adjudication of these outcomes by the Endpoint Adjudication Committee (EAC) were done in a blinded fashion. Event rate was estimated based on the time to the first occurrence of the event. (NCT01989754)
Timeframe: Approximately 3 years
| Intervention | Events per 1000 patient-years (Number) |
|---|
| Placebo | 11.60 |
| Canagliflozin (Experimental) | 10.06 |
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26
(NCT02025907)
Timeframe: Baseline and Week 26
| Intervention | percentage of glycosylated hemoglobin (Least Squares Mean) |
|---|
| Placebo | -0.01 |
| Canagliflozin | -0.91 |
Percentage of Participants With HbA1c Less Than (<) 7.0 Percent at Week 26
(NCT02025907)
Timeframe: Week 26
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 12.2 |
| Canagliflozin | 32.3 |
Percent Change From Baseline in Body Weight at Week 26
(NCT02025907)
Timeframe: Baseline and Week 26
| Intervention | percent change (Least Squares Mean) |
|---|
| Placebo | -1.60 |
| Canagliflozin | -3.35 |
Change From Baseline in Systolic Blood Pressure (SBP) at Week 26
(NCT02025907)
Timeframe: Baseline and Week 26
| Intervention | millimeter of mercury (mmHg) (Least Squares Mean) |
|---|
| Placebo | 0.09 |
| Canagliflozin | -5.76 |
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
(NCT02025907)
Timeframe: Baseline and Week 26
| Intervention | millimoles per liter (Least Squares Mean) |
|---|
| Placebo | -0.14 |
| Canagliflozin | -1.65 |
Cardiovascular (CV) Death
CV death included death due to MI, stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was a CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of CV death are presented. (NCT02065791)
Timeframe: Up to 4.6 years
| Intervention | Event rate per 1000 participant-years (Number) |
|---|
| Placebo | 24.38 |
| Canagliflozin 100 mg | 19.01 |
Composite Endpoint of CV Death and Hospitalized Heart Failure (HHF)
The composite endpoint included CV death and HHF. CV death included death due to myocardial infarction (MI), stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the composite endpoint of CV death and HHF are presented. (NCT02065791)
Timeframe: Up to 4.6 years
| Intervention | Event rate per 1000 participant-years (Number) |
|---|
| Placebo | 45.44 |
| Canagliflozin 100 mg | 31.47 |
CV Composite Endpoint
The CV composite endpoint included the CV death, non-fatal MI, non-fatal stroke, hospitalized heart failure, and hospitalized unstable angina. CV death included death due to MI, stroke, heart failure, sudden death, death during a CV procedure or as a result of procedure-related complications, or death due to other CV causes. For analytic purposes, undetermined causes of death were considered CV deaths. In determining whether a death event was a CV in nature, the EAC took into consideration both the proximate and underlying causes. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the CV composite endpoint are presented. (NCT02065791)
Timeframe: Up to 4.6 years
| Intervention | Event rate per 1000 participant-years (Number) |
|---|
| Placebo | 66.95 |
| Canagliflozin 100 mg | 49.35 |
Hospitalized Heart Failure (HHF)
Adjudication of these events by the Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of hospitalized heart failure are presented. (NCT02065791)
Timeframe: Up to 4.6 years
| Intervention | Event rate per 1000 participant-years (Number) |
|---|
| Placebo | 25.33 |
| Canagliflozin 100 mg | 15.65 |
Major Adverse Cardiac Event (MACE)
The composite endpoint included CV death, non-fatal MI, and non-fatal stroke (that is, 3-point MACE). Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of MACE are presented. (NCT02065791)
Timeframe: Up to 4.6 years
| Intervention | Event rate per 1000 participant-years (Number) |
|---|
| Placebo | 48.67 |
| Canagliflozin 100 mg | 38.71 |
Primary Composite Endpoint of Doubling of Serum Creatinine (DoSC), End-stage Kidney Disease (ESKD), and Renal or Cardiovascular (CV) Death
Primary composite endpoint is the composite of DoSC, ESKD, and renal or CV death. DoSC: from baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). ESKD: as initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an estimated glomerular filtration rate (eGFR) value of less than (<)15 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who had reached ESKD, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by Endpoint Adjudication Committee (EAC) was performed in blinded fashion. Event rate estimated based on time to first occurrence of primary composite endpoint are presented. (NCT02065791)
Timeframe: Up to 4.6 years
| Intervention | Event rate per 1000 participant-years (Number) |
|---|
| Placebo | 61.24 |
| Canagliflozin 100 mg | 43.21 |
All-cause Mortality
Adjudication of these events by Endpoint Adjudication Committee (EAC) was performed in a blinded fashion. Event rate estimated based on time to first occurrence of all-cause mortality are presented. (NCT02065791)
Timeframe: Up to 4.6 years
| Intervention | Event rate per 1000 participant-years (Number) |
|---|
| Placebo | 35.00 |
| Canagliflozin 100 mg | 29.04 |
Renal Composite Endpoint
The renal composite endpoint included composite of DoSC, ESKD and Renal death. DoSC: from the baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). ESKD: initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an eGFR value of <15 mL/min/1.73 m^2 (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who have reached ESKD, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the renal composite endpoint are presented. (NCT02065791)
Timeframe: Up to 4.6 years
| Intervention | Event rate per 1000 participant-years (Number) |
|---|
| Placebo | 40.36 |
| Canagliflozin 100 mg | 26.99 |
Percentage of Participants With Hemoglobin A1c (HbA1c) Reduction Greater Than or Equal to (>=) 0.4 Percent (%) and no Increase in Body Weight
Clinical response at Weeks 18 was assessed by the percentage of participants with Hemoglobin A1c (HbA1c) reduction greater than or equal to 0.4 % and had no increase in body weight. (NCT02139943)
Timeframe: Week 18
,,
| Intervention | percentage of participants (Number) |
|---|
| Yes | No |
|---|
| Canagliflozin 100 Milligram (mg) | 36.9 | 63.1 |
| Canagliflozin 300 mg | 41.4 | 58.6 |
| Placebo | 14.5 | 85.5 |
Percentage of Participants With Adverse Events
(NCT02139943)
Timeframe: Up to 22 Weeks
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 54.7 |
| Canagliflozin 100 Milligram (mg) | 55.6 |
| Canagliflozin 300 mg | 67.5 |
Change From Baseline in Fasting Plasma Glucose Level
The change from baseline in fasting plasma glucose level collected at Week 52. (NCT02220907)
Timeframe: Baseline, 52 Weeks
| Intervention | mg/dL (Mean) |
|---|
| Teneligliptin+Canagliflozin | -38.6 |
Percentage Change in Body Weight From Baseline
The percentage change from baseline in body weight collected at Week 52. (NCT02220907)
Timeframe: Baseline, 52 Weeks
| Intervention | percent change (Mean) |
|---|
| Teneligliptin+Canagliflozin | -3.92 |
Number of Participants With Adverse Events
(NCT02220907)
Timeframe: 52 Weeks
| Intervention | participants (Number) |
|---|
| Serious Adverse Event | Adverse Event |
|---|
| Teneligliptin+Canagliflozin | 11 | 107 |
Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c)
The change from baseline in percentage of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 52. (NCT02220907)
Timeframe: Baseline, 52 Weeks
| Intervention | percentage of HbA1c (Mean) |
|---|
| Teneligliptin+Canagliflozin | -0.99 |
"Percentage of Participants With Adverse Events and Hypoglycemia and Blood Glucose Decreased"
(NCT02220920)
Timeframe: Week 16
,
| Intervention | percentage of participants (Number) |
|---|
| adverse events | Hypoglycemia and Blood glucose decreased |
|---|
| Canagliflozin (TA-7284) ＋Insulin | 68.0 | 40.0 |
| Placebo＋Insulin | 64.8 | 29.6 |
Change in Blood Pressure
(NCT02220920)
Timeframe: baseline and Week 16
,
| Intervention | mmHg (Least Squares Mean) |
|---|
| Systolic blood pressure | Diastolic blood pressure |
|---|
| Canagliflozin (TA-7284) ＋Insulin | -3.58 | -1.55 |
| Placebo＋Insulin | -0.40 | -0.31 |
Change in Fasting Plasma Glucose
(NCT02220920)
Timeframe: baseline and Week 16
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Canagliflozin (TA-7284) ＋Insulin | -34.1 |
| Placebo＋Insulin | -1.4 |
Change in HbA1c From Baseline
(NCT02220920)
Timeframe: baseline and Week 16
| Intervention | Percent (Least Squares Mean) |
|---|
| Canagliflozin (TA-7284) ＋Insulin | -0.97 |
| Placebo＋Insulin | 0.13 |
Percent Change in Body Weight
(NCT02220920)
Timeframe: baseline and Week 16
| Intervention | percent change (Least Squares Mean) |
|---|
| Canagliflozin (TA-7284) ＋Insulin | -2.13 |
| Placebo＋Insulin | 0.24 |
Safety and Tolerability Assessed by Adverse Events (Number of Participants Experiencing With Adverse Events)
(NCT02227849)
Timeframe: 52 Weeks
| Intervention | Participants (Count of Participants) |
|---|
| Serious Adverse Event | Adverse Event |
|---|
| Canagliflozin (TA-7284) + GLP-1 Analogue | 5 | 51 |
Change in Blood Pressure
(NCT02227849)
Timeframe: Baseline, 52 Weeks
| Intervention | mmHg (Mean) |
|---|
| Systolic blood pressure | Diastolic blood pressure |
|---|
| Canagliflozin (TA-7284) + GLP-1 Analogue | -7.90 | -4.32 |
Percentage Change in Body Weight
(NCT02227849)
Timeframe: Baseline, 52 Weeks
| Intervention | percent change (Mean) |
|---|
| Canagliflozin (TA-7284) + GLP-1 Analogue | -4.46 |
Change in Percentage of HbA1c
(NCT02227849)
Timeframe: Baseline, 52 Weeks
| Intervention | percentage of HbA1c (Mean) |
|---|
| Canagliflozin (TA-7284) + GLP-1 Analogue | -0.70 |
Change in Fasting Plasma Glucose
(NCT02227849)
Timeframe: Baseline, 52 Weeks
| Intervention | mg/dL (Mean) |
|---|
| Canagliflozin (TA-7284) + GLP-1 Analogue | -34.7 |
Change From Baseline in Systolic Blood Pressure at Week 26
Change from baseline in systolic blood pressure was analysed at week 26. (NCT02243202)
Timeframe: Week 26
| Intervention | mmHg (millimeters of mercury) (Least Squares Mean) |
|---|
| Placebo | -2.7 |
| Phentermine 15 mg | -1.4 |
| Canagliflozin 300 mg | -3.1 |
| Canagliflozin 300 mg/Phentermine 15 mg | -6.9 |
Change From Baseline in Diastolic Blood Pressure (DBP) at Week 26
Change from baseline in diastolic blood pressure (DBP) at week 26. (NCT02243202)
Timeframe: Week 26
| Intervention | mmHg (millimeters of mercury) (Least Squares Mean) |
|---|
| Placebo | -0.9 |
| Phentermine 15 mg | 0.1 |
| Canagliflozin 300 mg | -1.5 |
| Canagliflozin 300 mg/Phentermine 15 mg | -2.5 |
Absolute Change From Baseline in Body Weight at Week 26
Absolute change from baseline in body weight was analysed at week 26. (NCT02243202)
Timeframe: Week 26
| Intervention | Kilogram (Kg) (Least Squares Mean) |
|---|
| Placebo | -0.6 |
| Phentermine 15 mg | -4.1 |
| Canagliflozin 300 mg | -1.9 |
| Canagliflozin 300 mg/Phentermine 15 mg | -7.3 |
Percentage of Participants With Weight Loss More Than Equal to (>=) 5 Percent at Week 26
Percentage of participants with weight loss >= 5 percent were analysed at week 26. (NCT02243202)
Timeframe: Week 26
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 17.5 |
| Phentermine 15 mg | 41.7 |
| Canagliflozin 300 mg | 17.9 |
| Canagliflozin 300 mg/Phentermine 15 mg | 66.7 |
Percentage of Participants With Weight Loss More Than Equal to (>=) 10 Percent at Week 26
Percentage of participants with weight loss >= 10 percent at week 26. (NCT02243202)
Timeframe: Week 26
| Intervention | Percentage of Participants (Number) |
|---|
| Placebo | 8.8 |
| Phentermine 15 mg | 8.3 |
| Canagliflozin 300 mg | 5.4 |
| Canagliflozin 300 mg/Phentermine 15 mg | 34.9 |
Change From Baseline in Pulse Rate at Week 26
Change from baseline in pulse rate at week 26 (NCT02243202)
Timeframe: Week 26
| Intervention | Beats Per Minute (Beats/Min) (Least Squares Mean) |
|---|
| Placebo | -0.7 |
| Phentermine 15 mg | 4.1 |
| Canagliflozin 300 mg | 0.7 |
| Canagliflozin 300 mg/Phentermine 15 mg | 3.5 |
Percent Change From Baseline in Body Weight at Week 26
The percent change from baseline in body weight at Week 26 was analysed. (NCT02243202)
Timeframe: Week 26
| Intervention | Percent Change (Least Squares Mean) |
|---|
| Placebo | -0.6 |
| Phentermine 15 mg | -4.1 |
| Canagliflozin 300 mg | -1.9 |
| Canagliflozin 300 mg/Phentermine 15 mg | -7.5 |
Change in 24-hour Blood Pressure at Study End Compared to Baseline.
Values will be presented as the mean + SD. The difference in HGP and all secondary endpoints at study end versus baseline will be calculated and compared between each active treatment group with ANOVA. (NCT02324842)
Timeframe: Approximately 4 months
| Intervention | mmHg (Mean) |
|---|
| Canagliflozin | -5.2 |
| Liraglutide | 5.1 |
| Canagliflozin Plus Liraglutide | -14.1 |
HbA1c at 4 Months
Primary end point of the study is the HbA1c level in response to canagliflozin alone, liraglutide or canagliflozin with liraglutide. (NCT02324842)
Timeframe: Approximately 4 months
| Intervention | percentage glycated hemoglobin (Mean) |
|---|
| Canagliflozin | 8.2 |
| Liraglutide | 8.4 |
| Canagliflozin Plus Liraglutide | 8.1 |
Fasting Plasma Glucose (FPG) at 4 Months
Values will be presented as the mean + (Standard Deviation) SD. The difference in HGP and all secondary endpoints at study end versus baseline will be calculated and compared between each active treatment group with ANOVA. (NCT02324842)
Timeframe: Baseline to Approximately 4 months
| Intervention | mg/dl (Mean) |
|---|
| Canagliflozin | 174 |
| Liraglutide | 177 |
| Canagliflozin Plus Liraglutide | 180 |
Change in Total Body Weight at Study End Compared to Baseline
Values will be presented as the mean + SD. The difference in HGP and all secondary endpoints at study end versus baseline will be calculated and compared between each active treatment group with ANOVA. The difference between baseline and study end will represent the change in body weight due to change in hepatic, visceral and abdominal subcutaneous fat. (NCT02324842)
Timeframe: Approximately 4 months
| Intervention | kg (Mean) |
|---|
| Canagliflozin | -3.5 |
| Liraglutide | -1.9 |
| Canagliflozin Plus Liraglutide | -6.0 |
Change in Plasma Glucagon Concentration at the End of the Study Compared to Baseline
Values will be presented as the mean + SD. The difference in HGP and all secondary endpoints at study end versus baseline will be calculated and compared between each active treatment group with ANOVA. (NCT02324842)
Timeframe: Approximately 4 months
| Intervention | mg/ml (Mean) |
|---|
| Canagliflozin | 12 |
| Liraglutide | -7 |
| Canagliflozin Plus Liraglutide | -5 |
Change in Matsuda Index of Insulin Sensitivity, Insulin Secretion, and Beta Cell Function During Oral Glucose Tolerance Test (OGTT)
Values will be presented as the mean + SD. The Matsuda Index is a novel assessment of insulin sensitivity that is simple to calculate and provides a reasonable approximation of whole-body insulin sensitivity from the OGTT. The index is calculated from plasma glucose (mg/dl) and insulin (mIU/l) concentrations in both fasting state and post-OGTT. The index value obtained is compared to normal physiologic values to assess insulin sensitivity or resistance. The higher the number, the more insulin sensitive and the lower the number the more insulin resistant the subjects are. Insulin secretion will be measured from plasma C-peptide concentration during the OGTT and the Mari Model will be used to measure beta cell glucose sensitivity (NCT02324842)
Timeframe: Change from Baseline to Approximately 4 months
| Intervention | index value (Mean) |
|---|
| Canagliflozin | 0.8 |
| Liraglutide | -0.5 |
| Canagliflozin Plus Liraglutide | 0.1 |
Change in Free Plasma Insulin at the End of the Study From Baseline Value
Values will be presented as the mean + SD. The difference in HGP and all secondary endpoints at study end versus baseline will be calculated and compared between each active treatment group with ANOVA. (NCT02324842)
Timeframe: At Approximately 4 months
| Intervention | mg/ml (Mean) |
|---|
| Canagliflozin | -2 |
| Liraglutide | 2 |
| Canagliflozin Plus Liraglutide | 0.7 |
Body Mass Index (BMI) at 4 Months
A measure of BMI at 4 months to examine effects of combination therapy with liraglutide plus canagliflozin. (NCT02324842)
Timeframe: Approximately 4 months
| Intervention | kg/m2 (Mean) |
|---|
| Canagliflozin | 34.8 |
| Liraglutide | 35.1 |
| Canagliflozin Plus Liraglutide | 34.8 |
Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c)
The change from baseline in percentage of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 24. (NCT02354222)
Timeframe: Baseline, 24 Weeks
| Intervention | percentage of HbA1c (Least Squares Mean) |
|---|
| Teneligliptin+Canagliflozin | -0.94 |
| Placebo+Canagliflozin | 0.00 |
Percentage Change in Body Weight From Baseline
The percentage change from baseline in body weight collected at Week 24. (NCT02354222)
Timeframe: Baseline, 24 Weeks
| Intervention | percent change (Least Squares Mean) |
|---|
| Teneligliptin+Canagliflozin | 0.09 |
| Placebo+Canagliflozin | -1.34 |
Change From Baseline in the AUC(0-2h) for Postprandial Plasma Glucose (PPG)
The change from Baseline in AUC(0-2h) for Postprandial Plasma Glucose collected at Week 24. (NCT02354222)
Timeframe: 0, 0.5, 1 and 2 hour postprandial, at Baseline and 24 Weeks
| Intervention | hour*mg/dL (Least Squares Mean) |
|---|
| Teneligliptin+Canagliflozin | -50.2 |
| Placebo+Canagliflozin | 5.7 |
Change From Baseline in Fasting Plasma Glucose Level
The change from baseline in fasting plasma glucose level collected at Week 24. (NCT02354222)
Timeframe: Baseline, 24 Weeks
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Teneligliptin+Canagliflozin | -5.6 |
| Placebo+Canagliflozin | 10.0 |
Change From Baseline in 2-hour Postprandial Plasma Glucose Level
The change from baseline in 2-hour postprandial plasma glucose level collected at Week 24. (NCT02354222)
Timeframe: 2 Hours Postprandial, at Baseline and 24 Weeks
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Teneligliptin+Canagliflozin | -35.3 |
| Placebo+Canagliflozin | 2.3 |
Percentage Change in Body Weight From Baseline
The percentage change from baseline in body weight collected at Week 24. (NCT02354235)
Timeframe: Baseline, 24 Weeks
| Intervention | percent change (Least Squares Mean) |
|---|
| Canagliflozin+Teneligliptin | -3.32 |
| Placebo+Teneligliptin | -0.99 |
Change From Baseline in 2-hour Postprandial Plasma Glucose Level
The change from baseline in 2-hour postprandial plasma glucose level collected at Week 24. (NCT02354235)
Timeframe: 2 Hours Postprandial, at Baseline and 24 Weeks
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Canagliflozin+Teneligliptin | -60.1 |
| Placebo+Teneligliptin | -9.2 |
Change From Baseline in the AUC(0-2h) for Postprandial Plasma Glucose (PPG)
The change from Baseline in AUC(0-2h) for Postprandial Plasma Glucose collected at Week 24. (NCT02354235)
Timeframe: 0, 0.5, 1 and 2 hour postprandial, at Baseline and 24 Weeks
| Intervention | hour*mg/dL (Least Squares Mean) |
|---|
| Canagliflozin+Teneligliptin | -105.9 |
| Placebo+Teneligliptin | -5.6 |
Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c)
The change from baseline in percentage of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 24. (NCT02354235)
Timeframe: Baseline, 24 Weeks
| Intervention | percentage of HbA1c (Least Squares Mean) |
|---|
| Canagliflozin+Teneligliptin | -0.97 |
| Placebo+Teneligliptin | -0.10 |
Change From Baseline in Fasting Plasma Glucose Level
The change from baseline in fasting plasma glucose level collected at Week 24. (NCT02354235)
Timeframe: Baseline, 24 Weeks
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Canagliflozin+Teneligliptin | -34.9 |
| Placebo+Teneligliptin | 3.9 |
Change in Body Composition, Measured Using DXA Scanning.
Body composition will be measured at baseline and at study completion using DXA scanning. (NCT02360774)
Timeframe: 18 weeks (duration of study)
| Intervention | % fat (Mean) |
|---|
| Canagliflozin | -0.2 |
| Placebo | -0.4 |
Change in Body Weight
Body weight will be measured at each study visit (screening visit, enrollment (study week 0), and at study weeks 2, 4, 8, 12 and 18). Change in body weight will be calculated using ANOVA such that body weight at all time points is included in the data analysis, rather than simply comparing weight at the enrollment visit to weight at the final study visit. (NCT02360774)
Timeframe: 18 weeks (duration of study)
| Intervention | kg (Mean) |
|---|
| Canagliflozin | 3.0 |
| Placebo | 0.3 |
Change in Glycemic Control
Hemoglobin A1C will be measured at baseline and at study completion. (NCT02360774)
Timeframe: 18 weeks (duration of study)
| Intervention | percent glycated hemoglobin (Mean) |
|---|
| Canagliflozin | -0.4 |
| Placebo | -0.1 |
Change in Resting Energy Expenditure, Measured Using Indirect Calorimetery
Resting energy expenditure will be measured at each study visit using indirect calorimetery. Data analysis will include change in REE from baseline to study conclusion, as well as change in REE throughout the study. (NCT02360774)
Timeframe: 18 weeks (duration of study)
| Intervention | kcal (Mean) |
|---|
| Canagliflozin | -60.8 |
| Placebo | -68.6 |
Canagliflozin-induced Change in Urinary Excretion of Sodium
The pharmacodynamic response to canagliflozin will be assessed by measuring the % increase in 24 hour urinary excretion of sodium. (NCT02462421)
Timeframe: 24 hours after administration of canagliflozin
| Intervention | % increase in urinary Na excretion (Mean) |
|---|
| Wild Type Genotype | 20 |
| Nonsense Mutation in SLC5A4 | 66 |
| Nonsense Mutation in SLC5A9 | 18 |
| Missense Variant in SLC2A9 | 48 |
| Total Population | 32 |
Change in Fractional Excretion of Uric Acid (the Difference Between Data After Administration of Canagliflozin Minus Data Before Administration of Canagliflozin)
For the study arm focused on individuals with a genetic variant in SLC2A9, the pharmacodynamic response to canagliflozin will be assessed by measuring the absolute change in fractional excretion of uric acid in the urine. Fractional excretion of uric acid represents the fraction of the calculated filtered uric acid load (serum uric acid level multiplied by the measured creatinine clearance rate) that was excreted in the urine. (NCT02462421)
Timeframe: 24 hour urine collection after administration of canagliflozin
| Intervention | absolute change in fractional excretion (Mean) |
|---|
| Wild Type Genotype | 0.25 |
| Nonsense Mutation in SLC5A4 | 0.25 |
| Nonsense Mutation in SLC5A9 | 0.28 |
| Missense Variant in SLC2A9 | 0.38 |
| Total Population | 0.29 |
Urinary Excretion of Glucose (Measured During the 24 Hours Following Administration of Canagliflozin)
The pharmacodynamic response to canagliflozin will be assessed by measuring the increase in 24 hour urinary glucose excretion. (NCT02462421)
Timeframe: 24 hours after administration of canagliflozin
| Intervention | glucose (g)/creatinine (g) (Mean) |
|---|
| Wild Type Genotype | 37.6 |
| Nonsense Mutation in SLC5A4 | 37.1 |
| Nonsense Mutation in SLC5A9 | 39.1 |
| Missense Variant in SLC2A9 | 36.9 |
| Total Population | 37.7 |
Canagliflozin-induced Change in Serum Creatinine
The pharmacodynamic response to canagliflozin will be assessed by measuring changes in serum creatinine (NCT02462421)
Timeframe: 24 hours after administration of canagliflozin
| Intervention | mg/dL (Mean) |
|---|
| Wild Type Genotype | 0.06 |
| Nonsense Mutation in SLC5A4 | -0.03 |
| Nonsense Mutation in SLC5A9 | 0.07 |
| Missense Variant in SLC2A9 | 0.05 |
| Total Population | 0.04 |
Canagliflozin-induced Change in Fasting Plasma Glucose
The magnitude of the change in fasting plasma glucose 24 hours after administration of canagliflozin (300 mg) (NCT02462421)
Timeframe: 24 hrs
| Intervention | mg/dL (Mean) |
|---|
| Wild Type Genotype | -5.0 |
| Nonsense Mutation in SLC5A4 | -2.0 |
| Nonsense Mutation in SLC5A9 | -4.7 |
| Missense Variant in SLC2A9 | -3.4 |
| Total Study Population | -4.2 |
Canagliflozin-induced Change in Serum Uric Acid
The pharmacodynamic response to canagliflozin will be assessed by measuring changes in serum uric acid level (NCT02462421)
Timeframe: 24 hours after administration of canagliflozin
| Intervention | % change in serum uric acid level (Mean) |
|---|
| Wild Type Genotype | -22 |
| Nonsense Mutation in SLC5A4 | -29 |
| Nonsense Mutation in SLC5A9 | -12 |
| Missense Variant in SLC2A9 | -17 |
| Total Study Population | -20 |
Change From Baseline in 6-Point Self-Monitored Plasma Glucose (SMPG) Profile at 24 Weeks
The self-monitored plasma glucose (SMPG) data were collected at the following 6 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening meal; 2 hours post-evening meal. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, metformin use, SGLT2 inhibitor use, country, visit, baseline HbA1c strata, and treatment-by-visit interaction as fixed effects and baseline as a covariate. (NCT02597049)
Timeframe: Baseline, Week 24
,,
| Intervention | mg/dL (Least Squares Mean) |
|---|
| Pre-morning Morning Meal | 2-Hour Postprandial Morning Meal | Pre-Mid Day Meal | 2-Hour Postprandial Mid Day Meal | Pre-Evening Meal | 2-Hour Postprandial Evening Meal |
|---|
| 0.75 mg Dulaglutide | -23.2 | -41.1 | -22.0 | -25.5 | -30.1 | -30.6 |
| 1.5 mg Dulaglutide | -27.8 | -44.6 | -26.0 | -31.8 | -30.3 | -36.0 |
| Placebo | -8.1 | -20.1 | -7.7 | -12.8 | -7.5 | -13.9 |
Change From Baseline in Body Weight at 24 Weeks
LS mean of the body weight change from baseline to primary endpoint at week 24 was adjusted by treatment, country, SGLT2 inhibitor dose, metformin use, baseline HbA1c strata, treatment-by-visit interactions as fixed effects, and baseline body weight as a covariate and participant as a random effect, via a MMRM analysis (NCT02597049)
Timeframe: Baseline, Week 24
,,
| Intervention | kilograms (kg) (Least Squares Mean) |
|---|
| Treatment-regimen Estimand | Efficacy Estimand |
|---|
| 0.75 mg Dulaglutide | -2.6 | -2.6 |
| 1.5 mg Dulaglutide | -3.1 | -3.1 |
| Placebo | -2.1 | -2.3 |
Change From Baseline in Fasting Serum Glucose (Central Laboratory) at 24 Weeks
LS mean of change from baseline was calculated using last observation carried forward (LOCF) by treatment group, adjusted for treatment, country, SGLT2 inhibitor dose, metformin use, baseline HbA1c strata, and baseline fasting serum glucose using analysis of covariance (ANCOVA). (NCT02597049)
Timeframe: Baseline, Week 24
,,
| Intervention | milligram/deciliter (mg/dL) (Least Squares Mean) |
|---|
| Treatment-regimen Estimand | Efficacy Estimand |
|---|
| 0.75 mg Dulaglutide | -26.5 | -26.0 |
| 1.5 mg Dulaglutide | -31.6 | -31.9 |
| Placebo | -6.9 | -5.3 |
Number of Participants With Adjudicated Cardiovascular (CV) Events
Death and selected nonfatal CV adverse events (AEs) were adjudicated by an independent committee of physicians with cardiology expertise external to the Sponsor. Nonfatal CV events that were to be adjudicated were myocardial infarction (MI); hospitalization for unstable angina; hospitalization for heart failure; coronary interventions such as coronary artery bypass graft (CABG) or ( percutaneous coronary intervention (PCI); and cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic attack (TIA). (NCT02597049)
Timeframe: Baseline through 24 Weeks
,,
| Intervention | Participants (Count of Participants) |
|---|
| Any CV Event | Fatal CV Event | Non-fatal CV Event |
|---|
| 0.75 mg Dulaglutide | 0 | 0 | 0 |
| 1.5 mg Dulaglutide | 0 | 0 | 0 |
| Placebo | 3 | 0 | 3 |
Percentage of Participants With HbA1c <7%
Number of participants with an HbA1c value of <7% at Week 24 is measured using longitudinal logistic regression with repeated measurements. The model will include independent variables of treatment, country, SGLT2 inhibitor dose, metformin use, visit, treatment-by-visit interaction, and baseline HbA1c as a covariate. (NCT02597049)
Timeframe: 24 Weeks
,,
| Intervention | percentage of participants (Number) |
|---|
| Treatment-regimen Estimand | Efficacy Estimand |
|---|
| 0.75 mg Dulaglutide | 60.45 | 61.83 |
| 1.5 mg Dulaglutide | 71.21 | 71.54 |
| Placebo | 31.58 | 32.52 |
Rate of Hypoglycemic Events Adjusted Per 30 Days
A hypoglycemic event is defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a PG level of ≤70 mg/dL (≤3.9 mmol/L). (NCT02597049)
Timeframe: Baseline through 24 Weeks
,,
| Intervention | Number of events/participant/30 days (Mean) |
|---|
| Total Hypoglycemia | Documented Symptomatic Hypoglycemia | Asymptomatic Hypoglycemia | Probable Symptomatic | Relative Hypoglycemia | Nocturnal Hypoglycemia |
|---|
| 0.75 mg Dulaglutide | 0.022 | 0.013 | 0.008 | 0.001 | 0.001 | 0.009 |
| 1.5 mg Dulaglutide | 0.026 | 0.013 | 0.013 | 0.000 | 0.003 | 0.002 |
| Placebo | 0.017 | 0.010 | 0.006 | 0.001 | 0.005 | 0.000 |
Change From Baseline in the HbA1c at 24 Weeks (Efficacy Estimand)
LS mean of the HbA1c change from baseline to primary endpoint at week 24 was adjusted by treatment, country, SGLT2 inhibitor dose, metformin use, treatment-by-visit interactions as fixed effects, and baseline HbA1c as a covariate and participant as a random effect, via a MMRM analysis. The efficacy estimand excluded post-rescue data and compared the benefit of randomized treatments when taken as directed without rescue medication. (NCT02597049)
Timeframe: Baseline, Week 24
| Intervention | percentage of HbA1c (Least Squares Mean) |
|---|
| 1.5 mg Dulaglutide | -1.33 |
| 0.75 mg Dulaglutide | -1.19 |
| Placebo | -0.51 |
Change From Baseline in Hemoglobin A1c (HbA1c) at 24 Weeks (Treatment-regimen Estimand)
Least Squares mean (LS) of the HbA1c change from baseline to primary endpoint at week 24 was adjusted by treatment, country, SGLT2 inhibitor dose, metformin use, treatment-by-visit interactions as fixed effects, and baseline HbA1c as a covariate and participant as a random effect, via a MMRM analysis. The treatment-regimen estimand used all data including post-rescue data and compared the benefit of treatment regimens as they were actually taken. (NCT02597049)
Timeframe: Baseline, Week 24
| Intervention | percentage of HbA1c (Least Squares Mean) |
|---|
| 1.5 mg Dulaglutide | -1.34 |
| 0.75 mg Dulaglutide | -1.21 |
| Placebo | -0.54 |
Change From Baseline in Fasting Glucagon at 24 Weeks
Change from baseline in fasting glucagon was analyzed using an ANCOVA model with last observation carried forward (LOCF) included in treatment, country, SGLT2i dose, metformin use, and baseline HbA1c strata as fixed effects and baseline fasting glucagon as a covariate (with and without post rescue data). (NCT02597049)
Timeframe: Baseline, Week 24
,,
| Intervention | picomole per liter (pmol/L) (Least Squares Mean) |
|---|
| Treatment-regimen Estimand | Efficacy Estimand |
|---|
| 0.75 mg Dulaglutide | -1.5 | -1.4 |
| 1.5 mg Dulaglutide | -2.1 | -2.2 |
| Placebo | -0.9 | -0.9 |
Number of Participants Requiring Rescue Therapy Due to Severe Persistent Hyperglycemia
Rescue therapy was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. (NCT02597049)
Timeframe: Baseline through 24 Weeks
| Intervention | Participants (Count of Participants) |
|---|
| 1.5 mg Dulaglutide | 0 |
| 0.75 mg Dulaglutide | 3 |
| Placebo | 2 |
Number of Participants With Adjudicated Acute Pancreatitis Events
"The number of participants with events of pancreatitis confirmed by adjudication were summarized cumulatively at 24 weeks. Pancreatitis events were adjudicated by a committee of physicians external to the Sponsor.~A summary of serious and other non-serious events regardless of causality is located in the Reported Adverse Events module." (NCT02597049)
Timeframe: Baseline through 24 Weeks
| Intervention | Participants (Count of Participants) |
|---|
| 1.5 mg Dulaglutide | 0 |
| 0.75 mg Dulaglutide | 0 |
| Placebo | 0 |
Percentage Change in Body Weight
(NCT02622113)
Timeframe: Placebo/CANA: Baseline, 36 Weeks; CANA/CANA: Baseline, 52 Weeks
| Intervention | percent change (Mean) |
|---|
| Placebo/CANA + Insulin | -1.40 |
| CANA/CANA + Insulin | -2.14 |
Change in Percentage of HbA1c
(NCT02622113)
Timeframe: Placebo/CANA: Baseline, 36 Weeks; CANA/CANA: Baseline, 52 Weeks
| Intervention | percentage of HbA1c (Mean) |
|---|
| Placebo/CANA + Insulin | -1.09 |
| CANA/CANA + Insulin | -0.88 |
Change in Fasting Plasma Glucose
(NCT02622113)
Timeframe: Placebo/CANA: Baseline, 36 Weeks; CANA/CANA: Baseline, 52 Weeks
| Intervention | mg/dL (Mean) |
|---|
| Placebo/CANA + Insulin | -33.1 |
| CANA/CANA + Insulin | -32.8 |
Safety and Tolerability Assessed by Adverse Events (Number of Participants Experiencing With Adverse Events)
(NCT02622113)
Timeframe: Placebo/CANA: 36 Weeks, CANA/CANA: 52 Weeks
,
| Intervention | Participants (Count of Participants) |
|---|
| Serious Adverse Event | Adverse Event |
|---|
| CANA/CANA + Insulin | 7 | 69 |
| Placebo/CANA + Insulin | 7 | 57 |
Differences in Free Fatty Acid Levels Following Interruption of Basal Subcutaneous Insulin Infusion
(NCT02673138)
Timeframe: 20 hours
| Intervention | mmol/L (Mean) |
|---|
| Basal Interruption | 0.8 |
| Basal Interruption With Canagliflozin | 0.7 |
Differences in Plasma Glucose Levels Following the Interruption of Basal Subcutaneous Infusion of Insulin
The primary outcome measure for this study will be differences in plasma glucose levels following the interruption of basal subcutaneous infusion of insulin under the two study conditions; i.e., control study during treatment with insulin alone vs. experimental study during treatment with insulin plus canagliflozin or other SGLT2 inhibitor. (NCT02673138)
Timeframe: 20 hours
| Intervention | mg/dL (Mean) |
|---|
| Basal Interruption | 197 |
| Basal Interruption With Canagliflozin | 99 |
Differences in BHB (Beta-hydroxybutyrate) Levels Following Interruption of Basal
(NCT02673138)
Timeframe: 20 hours
| Intervention | mmol/L (Mean) |
|---|
| Basal Interruption | 1.2 |
| Basal Interruption With Canagliflozin | 1.5 |
Differences in Glucagon Levels Following the Interruption of the Basal Subcutaneous Insulin Infusion
(NCT02673138)
Timeframe: 20 hours
| Intervention | pg/mL (Mean) |
|---|
| Basal Interruption | 14 |
| Basal Interruption With Canagliflozin | 36 |
Change at Six Months Versus Baseline in Hemoglobin A1c Value (%)
The change in hemoglobin A1c from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery (NCT02912455)
Timeframe: 6 months
| Intervention | percentage (Mean) |
|---|
| Study Drug (Canagliflozin) | -0.31 |
| Placebo | 0.11 |
Change in Adiponectin Levels at 6 Months Compared to Randomization
The change in adiponectin levels from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery. (NCT02912455)
Timeframe: 6 months
| Intervention | ug/mL (Mean) |
|---|
| Study Drug (Canagliflozin) | 0.7 |
| Placebo | -3.4 |
Change in Body Weight at Six Months Compared to Baseline
The change in body weight from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery. (NCT02912455)
Timeframe: 6 months
| Intervention | kilograms (Mean) |
|---|
| Study Drug (Canagliflozin) | -3.77 |
| Placebo | 6.33 |
Change in CRP Levels at 6 Months Compared to Baseline
The change in C-reactive protein levels from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery. (NCT02912455)
Timeframe: 6 months
| Intervention | mg/L (Mean) |
|---|
| Study Drug (Canagliflozin) | -5.35 |
| Placebo | 3.34 |
Change in Diastolic Blood Pressure at Six Months Compared to Baseline
The change in diastolic blood pressure from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery (NCT02912455)
Timeframe: 6 months
| Intervention | mmHg (Mean) |
|---|
| Study Drug (Canagliflozin) | -1.18 |
| Placebo | 2.95 |
Change in Fasting Glucose From Randomization
The change in fasting glucose from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery. (NCT02912455)
Timeframe: 6 months
| Intervention | mg/dL (Mean) |
|---|
| Study Drug (Canagliflozin) | -32.90 |
| Placebo | -44.61 |
Change in Percentage of Truncal Fat
Change in percentage of truncal fat as measured by DEXA scan at 6 months compared to randomization (NCT02912455)
Timeframe: 6 months
| Intervention | percent change (Mean) |
|---|
| Study Drug (Canagliflozin) | -2.67 |
| Placebo | 2.74 |
Change in Spine Bone Mineral Density
Change in spine bone marrow density as measured by DEXA scan at 6 months compared to randomization (NCT02912455)
Timeframe: 6 months
| Intervention | grams per square centimeter (Mean) |
|---|
| Study Drug (Canagliflozin) | -0.02 |
| Placebo | 0.14 |
Change in Percentage of Lean Mass
Change in percentage of lean body mass as measured by DEXA scan at 6 months compared to randomization (NCT02912455)
Timeframe: 6 months
| Intervention | percent change (Mean) |
|---|
| Study Drug (Canagliflozin) | 1.82 |
| Placebo | -2.65 |
Change in Percentage of Gynoid Fat
Change in percentage of gynoid fat as measured by DEXA scan at 6 months compared to randomization (NCT02912455)
Timeframe: 6 months
| Intervention | percent change (Mean) |
|---|
| Study Drug (Canagliflozin) | -1.69 |
| Placebo | 2.17 |
Change in Percentage of Android Fat
Change in percentage of android fat as measured by DEXA scan at 6 months compared to randomization (NCT02912455)
Timeframe: 6 months
| Intervention | percent change (Mean) |
|---|
| Study Drug (Canagliflozin) | -3.00 |
| Placebo | 3.33 |
Change in Percent Body Fat as Measured by DEXA Scan at 6 Months Compared to Randomization
The change in body fat from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery. (NCT02912455)
Timeframe: 6 months
| Intervention | percent change (Mean) |
|---|
| Study Drug (Canagliflozin) | -1.82 |
| Placebo | 2.65 |
Change in Leptin Levels at 6 Months Compared to Baseline
Change in leptin levels at 6 months compared to baseline The change in leptin levels from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery. (NCT02912455)
Timeframe: 6 months
| Intervention | ng/mL (Mean) |
|---|
| Study Drug (Canagliflozin) | -8.1 |
| Placebo | -11 |
Number of Participants Who Reported Hypoglycemia From Each Group (at a Frequency of 1 Episode)
The number of participants who reported symptomatic hypoglycemia episodes from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery. (NCT02912455)
Timeframe: 6 months
| Intervention | participants (Number) |
|---|
| Study Drug (Canagliflozin) | 2 |
| Placebo | 0 |
Change in Leg Bone Mineral Density
Change in leg bone marrow density as measured by DEXA scan at 6 months compared to randomization (NCT02912455)
Timeframe: 6 months
| Intervention | grams per square centimeter (Mean) |
|---|
| Study Drug (Canagliflozin) | 0.01 |
| Placebo | -0.04 |
Change in Total Cholesterol
The change in total cholesterol from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery (NCT02912455)
Timeframe: 6 months
| Intervention | mg/dL (Mean) |
|---|
| Study Drug (Canagliflozin) | -0.87 |
| Placebo | 3.69 |
Change in Systolic Blood Pressure at 6 Months Compared to Baseline
The Change in Systolic Blood Pressure From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery (NCT02912455)
Timeframe: 6 months
| Intervention | mmHg (Mean) |
|---|
| Study Drug (Canagliflozin) | 4.62 |
| Placebo | 12.63 |
Change From Baseline Ventilatory Efficiency at 12 Weeks
Minute ventilation (VE) relative to CO2 production (VCO2) slope measured by cardiopulmonary exercise test (NCT02920918)
Timeframe: baseline and 12 weeks
| Intervention | Unitless (Mean) |
|---|
| Canagliflozin | -0.3 |
| Sitagliptin | -0.3 |
Change From Baseline Aerobic Exercise Capacity at 12 Weeks
Peak oxygen consumption (VO2) measured by maximal cardiopulmonary exercise test (NCT02920918)
Timeframe: baseline and 12 weeks
| Intervention | mL/kg/min (Mean) |
|---|
| Canagliflozin | 0.67 |
| Sitagliptin | -0.53 |
Glycemic Control
Measured from blood glucose values (fasting) during visit (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment reported
| Intervention | mg/dL (Mean) |
|---|
| Active Arm | 142.79 |
| Placebo Arm | 158.0 |
Glycemic Control (HbA1C)
As determined by HbA1C values (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment reported
| Intervention | percentage of hemoglobin (Mean) |
|---|
| Active Arm | 7.85 |
| Placebo Arm | 8.26 |
Microalbumin
Creatinine Clearance and Kidney Function measured from compiled results from a urine sample and blood tests (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment reported
| Intervention | mg/g creatinine (Mean) |
|---|
| Active Arm | 33.97 |
| Placebo Arm | 43.41 |
Pulse Wave Velocity
Vessel health assessed by using arterial tonometry with the SphygmoCor CP system from ATCOR . (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment reported (also measured at 8 weeks)
| Intervention | m/s (Mean) |
|---|
| Active Arm | 10.12 |
| Placebo Arm | 11.42 |
Serum Endothelial Inflammatory Markers (2)
Highly selective C-reactive protein (hs-CRP) (NCT02964585)
Timeframe: measured at 8 and 16 (reported) weeks post treatment
| Intervention | mg/L (Mean) |
|---|
| Active Arm | 0.63 |
| Placebo Arm | 0.92 |
Augmentation Index (Pulse Wave Analysis)
Vessel health assessed by using arterial tonometry with the SphygmoCor CP system from ATCOR. Higher values generally correlate with increased cardiovascular risk. (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment reported (also measured at 8 weeks)
| Intervention | percent aug pressure of pulse pressure (Mean) |
|---|
| Active Arm | 28.67 |
| Placebo Arm | 21.37 |
Body Fat Percentage
Measured using a Tanita body composition scale (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment
| Intervention | percentage of body mass (Mean) |
|---|
| Active Arm | 32.46 |
| Placebo Arm | 38.58 |
eGFR
Creatinine Clearance and Kidney Function measured from compiled results from a urine sample and blood tests (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment reported
| Intervention | mL/min (Mean) |
|---|
| Active Arm | 79.90 |
| Placebo Arm | 88.33 |
Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Proliferation)
To determine whether 4 months of Canagliflozin modifies CD34+ cell number, gene expression and migration function. The investigators will obtain a total of approximately 95 mL of peripheral blood per visit. Of these 95 mL, 60-70 mL will be used to obtain CD34+ cells from mononuclear cell (MNC) population and 25-35 mL for biochemistry and plasma ELISA assays. MNC will be obtained from whole blood similar to protocols described before [13,14]. MNCs will be put through CD34 magnetic bead column to obtain CD34+ cells (Miltenyi Biotec). Purity of CD34+ cells, post sort, usually is above 90%, to be verified by FACS analysis. (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment reported
| Intervention | Colony forming units (CFU) (Mean) |
|---|
| Active Arm | 7.53 |
| Placebo Arm | 13.69 |
Fasting Lipid Profile
Measured from a serum blood Lipid Panel: cholesterol and serum ketone bodies (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment reported (also measured at 8 weeks)
,
| Intervention | mg/dL (Mean) |
|---|
| Cholesterol | HDL | LDL | 3-hydroxybutyric acid (ketone body) | Acetoacetic acid (ketone body) |
|---|
| Active Arm | 171.57 | 46.17 | 96.03 | 0.02 | 0.69 |
| Placebo Arm | 147.76 | 51.67 | 82.672 | 0.03 | 0.30 |
Creatinine (Urine)
Creatinine Clearance and Kidney Function measured from compiled results from a urine sample and blood tests (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment reported
| Intervention | mmol/L (Mean) |
|---|
| Active Arm | 77.08 |
| Placebo Arm | 106.23 |
BMI
Determined as weight in kg divided by height in meters squared (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment
| Intervention | kg/m^2 (Mean) |
|---|
| Active Arm | 30.53 |
| Placebo Arm | 34.64 |
Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Counts)
To determine whether 4 months of Canagliflozin modifies CD34+ cell number, gene expression and migration function. The investigators will obtain a total of approximately 95 mL of peripheral blood per visit. Of these 95 mL, 60-70 mL will be used to obtain CD34+ cells from mononuclear cell (MNC) population and 25-35 mL for biochemistry and plasma ELISA assays. MNC will be obtained from whole blood similar to protocols described before [13,14]. MNCs will be put through CD34 magnetic bead column to obtain CD34+ cells (Miltenyi Biotec). Purity of CD34+ cells, post sort, usually is above 90%, to be verified by FACS analysis. (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment reported
,
| Intervention | cells*10^6/mL (Mean) |
|---|
| Mean MNC count | Mean CD34+ve cell count (x100) |
|---|
| Active Arm | 155.09 | 2682.93 |
| Placebo Arm | 155.09 | 3157.36 |
Serum Endothelial Inflammatory Markers (1)
IL-6, and TNF-alpha (NCT02964585)
Timeframe: measured at 8 and 16 (reported) weeks post treatment
,
| Intervention | pg/mL (Mean) |
|---|
| IL-6 | TNF-alpha |
|---|
| Active Arm | 4.56 | 1.36 |
| Placebo Arm | 3.21 | 1.63 |
Kidney Function Markers
Creatinine Clearance and Kidney Function measured from compiled results from a urine sample and blood tests (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment reported
,
| Intervention | ug/dL (Mean) |
|---|
| PODXL | Nephrin | Wilm's Tumor |
|---|
| Active Arm | 6.62 | 5.24 | 5.75 |
| Placebo Arm | 6.68 | 5.87 | 6.36 |
Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Protein Expression)
To determine whether 4 months of Canagliflozin modifies CD34+ cell number, gene expression and migration function. The investigators will obtain a total of approximately 95 mL of peripheral blood per visit. Of these 95 mL, 60-70 mL will be used to obtain CD34+ cells from mononuclear cell (MNC) population and 25-35 mL for biochemistry and plasma ELISA assays. MNC will be obtained from whole blood similar to protocols described before [13,14]. MNCs will be put through CD34 magnetic bead column to obtain CD34+ cells (Miltenyi Biotec). Purity of CD34+ cells, post sort, usually is above 90%, to be verified by FACS analysis. (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment reported
,
| Intervention | ng/mL in serum (Mean) |
|---|
| CXCL12 Expression | CXCR4 Expression | EDN1 | VEGEF-A | PECAM | KDR | NOS3 | Catalase | GPX35 | SDF 10 NG | SOD2 |
|---|
| Active Arm | 0.63 | 1.58 | 2.10 | 1.12 | 1.28 | 1.16 | 0.34 | 0.20 | 2.25 | 0.26 | 1.36 |
| Placebo Arm | 0.33 | 0.90 | 1.03 | 0.83 | 0.89 | 0.5 | -0.25 | -0.61 | 1.71 | 0.23 | 0.92 |
Gene Expression and Function Change of CD34+ Endothelial Progenitor Cells (Cell Percentages)
To determine whether 4 months of Canagliflozin modifies CD34+ cell number, gene expression and migration function. The investigators will obtain a total of approximately 95 mL of peripheral blood per visit. Of these 95 mL, 60-70 mL will be used to obtain CD34+ cells from mononuclear cell (MNC) population and 25-35 mL for biochemistry and plasma ELISA assays. MNC will be obtained from whole blood similar to protocols described before [13,14]. MNCs will be put through CD34 magnetic bead column to obtain CD34+ cells (Miltenyi Biotec). Purity of CD34+ cells, post sort, usually is above 90%, to be verified by FACS analysis. (NCT02964585)
Timeframe: 16 weeks post Canagliflozin treatment reported
,
| Intervention | percentage of MNCs (Mean) |
|---|
| Percent of CD34+ | Percent of CD31+ | Percent CD34+ and CD184+ |
|---|
| Active Arm | 0.93 | 2.58 | 0.37 |
| Placebo Arm | 1.23 | 2.16 | 0.61 |
Change in Total Fat Mass (kg)
Change from baseline (week 0) to week 52 in total fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | kg (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | -3.72 |
| Canagliflozin + Semaglutide Placebo | -2.63 |
Change in SMPG- Mean Postprandial Increment Over All Meals
Change from baseline (week 0) to week 52 in SMPG- mean postprandial increment over all meals was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | mmol/L (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | -0.6 |
| Canagliflozin + Semaglutide Placebo | -0.6 |
Change in SMPG (Self-measured Plasma Glucose)- Mean 7-point Profile
Change from baseline (week 0) to week 52 in SMPG- mean 7-point profile was evaluated. SMPG was recorded at the following 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after dinner and at bedtime. Mean 7-point profile was defined as the area under the profile, calculated using the trapezoidal method, divided by the measurement time. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | mmol/L (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | -2.8 |
| Canagliflozin + Semaglutide Placebo | -1.9 |
Change in SF-36: Physical Component Summary (PCS)
Change from baseline (week 0) to week 52 in short form 36 v2.0 acute domain PCS. SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. It consists of 2 component summary measures that further summarize 8 health domain scales. The PCS measure is derived from domain scales of physical functioning, role-physical, bodily pain, and general health. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. A positive change score indicates an improvement since baseline. Results are based on the 'on-treatment without rescue medication' observation period. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Score on a scale (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 2.7 |
| Canagliflozin + Semaglutide Placebo | 2.9 |
Change in SF-36: Mental Component Summary (MCS)
Change from baseline (week 0) to week 52 in short form 36 v2.0 acute domain MCS. SF- 36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The MCS measure is derived from domain scales of vitality, social functioning, role emotional and mental health. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. A positive change score indicates an improvement since baseline. Results are based on the 'on-treatment without rescue medication' observation period. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Score on a scale (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 1.1 |
| Canagliflozin + Semaglutide Placebo | 0.5 |
Change in Ratio Between Total Fat Mass and Total Lean Mass
Change from baseline (week 0) to week 52 in ratio between total fat mass and total lean mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | total fat mass/total lean mass ratio (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | -0.04 |
| Canagliflozin + Semaglutide Placebo | -0.03 |
Change in Pulse
Change from baseline (week 0) to week 52 in pulse is presented based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Beats per minute (beats/min) (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 2.7 |
| Canagliflozin + Semaglutide Placebo | -0.6 |
Participants Who Achieved Weight Loss ≥5% (Yes/no)
Percentage of participants losing ≥5% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Percentage of participants (Number) |
|---|
| Yes | No |
|---|
| Canagliflozin + Semaglutide Placebo | 47.0 | 53.0 |
| Semaglutide + Canagliflozin Placebo | 52.7 | 47.3 |
Participants Who Achieved Weight Loss ≥3% (Yes/no)
Percentage of participants losing ≥3% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Percentage of participants (Number) |
|---|
| Yes | No |
|---|
| Canagliflozin + Semaglutide Placebo | 64.9 | 35.1 |
| Semaglutide + Canagliflozin Placebo | 68.8 | 31.2 |
Participants Who Achieved Weight Loss ≥10% (Yes/no)
Percentage of participants losing ≥10% of baseline body weight is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Percentage of participants (Number) |
|---|
| Yes | No |
|---|
| Canagliflozin + Semaglutide Placebo | 8.9 | 91.1 |
| Semaglutide + Canagliflozin Placebo | 23.2 | 76.8 |
Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥5% (Yes/no)
Percentage of participants who achieved ≥1% reduction of baseline HbA1c and losing ≥5% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Percentage of participants (Number) |
|---|
| Yes | No |
|---|
| Canagliflozin + Semaglutide Placebo | 25.9 | 74.1 |
| Semaglutide + Canagliflozin Placebo | 45.1 | 54.9 |
Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥3% (Yes/no)
Percentage of participants who achieved ≥1% reduction of baseline HbA1c and losing ≥3% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Percentage of participants (Number) |
|---|
| Yes | No |
|---|
| Canagliflozin + Semaglutide Placebo | 34.8 | 65.2 |
| Semaglutide + Canagliflozin Placebo | 57.3 | 42.7 |
Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥10% (Yes/no)
Percentage of participants who achieved ≥1% reduction of baseline HbA1c and losing ≥10% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Percentage of participants (Number) |
|---|
| Yes | No |
|---|
| Canagliflozin + Semaglutide Placebo | 6.1 | 93.9 |
| Semaglutide + Canagliflozin Placebo | 21.8 | 78.2 |
Participants Who Achieved HbA1c Reduction ≥1% (Yes/no)
Percentage of participants who achieved ≥1% reduction of baseline HbA1c (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Percentage of participants (Number) |
|---|
| Yes | No |
|---|
| Canagliflozin + Semaglutide Placebo | 48.6 | 51.4 |
| Semaglutide + Canagliflozin Placebo | 76.5 | 23.5 |
Participants Who Achieved HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/no)
Severe or BG-confirmed symptomatic hypoglycaemia is an episode that is severe according to the American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value <3.1 mmol/L (56 milligrams per deciliter [mg/dL]) with symptoms consistent with hypoglycaemia. Percentage of participants who achieved HbA1c below 7.0% (53 mmol/mol) without severe or blood glucose confirmed symptomatic hypoglycaemia episodes and no weight gain (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Percentage of participants (Number) |
|---|
| Yes | No |
|---|
| Canagliflozin + Semaglutide Placebo | 45.0 | 55.0 |
| Semaglutide + Canagliflozin Placebo | 69.6 | 30.4 |
Participants Who Achieved HbA1c ≤ 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE) Target (Yes/no)
Percentage of participants who achieved HbA1c ≤ 6.5% (48 mmol/mol), AACE target (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 52
,
| Intervention | Percentage of participants (Number) |
|---|
| Yes | No |
|---|
| Canagliflozin + Semaglutide Placebo | 26.8 | 73.2 |
| Semaglutide + Canagliflozin Placebo | 62.1 | 37.9 |
Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol), American Diabetes Association (ADA) Target (Yes/no)
Percentage of participants who achieved HbA1c < 7.0% (53 millimoles per mole [mmol/mol]), ADA target (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 52
,
| Intervention | Percentage of participants (Number) |
|---|
| Yes | No |
|---|
| Canagliflozin + Semaglutide Placebo | 50.8 | 49.2 |
| Semaglutide + Canagliflozin Placebo | 76.1 | 23.9 |
Change in Haematological Parameter- Leukocytes
Change from baseline (week 0) to week 52 in leukocytes (10^9 cells/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of leukocytes (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 0.97 |
| Canagliflozin + Semaglutide Placebo | 0.98 |
Change in Haematological Parameter- Haemoglobin
Change from baseline (week 0) to week 52 in haemoglobin (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of haemoglobin (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 0.99 |
| Canagliflozin + Semaglutide Placebo | 1.05 |
Change in Haematological Parameter- Haematocrit
Change from baseline (week 0) to week 52 in haematocrit (%) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of haematocrit (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 0.99 |
| Canagliflozin + Semaglutide Placebo | 1.04 |
Change in Haematological Parameter- Erythrocytes
Change from baseline (week 0) to week 52 in erythrocytes (10^12 cells/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of erythrocytes (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 0.99 |
| Canagliflozin + Semaglutide Placebo | 1.04 |
Change in FPG (Fasting Plasma Glucose)
Change from baseline (week 0) to week 52 in FPG was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Millimoles per liter (mmol/L) (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | -2.54 |
| Canagliflozin + Semaglutide Placebo | -2.00 |
Change in Fasting Triglycerides
Change from baseline (week 0) to week 52 in fasting triglycerides (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of triglycerides (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 0.86 |
| Canagliflozin + Semaglutide Placebo | 0.92 |
Change in Fasting Total Cholesterol
Change from baseline (week 0) to week 52 in fasting total cholesterol (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of total cholesterol (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 0.96 |
| Canagliflozin + Semaglutide Placebo | 1.03 |
Change in Fasting LDL-cholesterol
Change from baseline (week 0) to week 52 in fasting low-density lipoprotein (LDL) cholesterol (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of LDL-cholesterol (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 0.96 |
| Canagliflozin + Semaglutide Placebo | 1.05 |
Change in Fasting HDL-cholesterol
Change from baseline (week 0) to week 52 in fasting high-density lipoprotein (HDL) cholesterol (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of HDL-cholesterol (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 1.04 |
| Canagliflozin + Semaglutide Placebo | 1.08 |
Change in Calcitonin
Change from baseline (week 0) to week 52 in calcitonin (nanograms per liter) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of calcitonin (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 1.08 |
| Canagliflozin + Semaglutide Placebo | 1.04 |
Change in Body Weight (kg)
Change from baseline (week 0) to week 52 in body weight was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Kilogram (kg) (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | -5.7 |
| Canagliflozin + Semaglutide Placebo | -4.3 |
Change in Body Mass Index (BMI)
Change from baseline (week 0) to week 52 in BMI was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Kilogram per square meter (kg/m^2) (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | -2.0 |
| Canagliflozin + Semaglutide Placebo | -1.5 |
Change in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure)
Change from baseline (week 0) to week 52 in systolic blood pressure and diastolic blood pressure. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Millimeters of mercury (mmHg) (Mean) |
|---|
| Systolic blood pressure | Diastolic blood pressure |
|---|
| Canagliflozin + Semaglutide Placebo | -5.8 | -2.9 |
| Semaglutide + Canagliflozin Placebo | -3.7 | -1.2 |
Change in Short Form 36 Health Survey (SF-36): Sub-domains
SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline (week 0) to week 52 in the sub-domain scores is presented. A positive change score indicate an improvement since baseline. Results are based on the 'on-treatment without rescue medication' observation period. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Score on a scale (Mean) |
|---|
| Physical Functioning | Role-physical | Bodily pain | General health | Social functioning | Role-emotional | Vitality | Mental health |
|---|
| Canagliflozin + Semaglutide Placebo | 2.7 | 2.0 | 1.5 | 3.5 | 1.1 | 1.2 | 2.0 | 0.6 |
| Semaglutide + Canagliflozin Placebo | 1.9 | 1.8 | 2.5 | 3.7 | 1.1 | 0.8 | 3.0 | 1.5 |
Change in Physical Examination
Physical examination parameters are categorised as general appearance; nervous system (central and peripheral); cardiovascular system; gastrointestinal system; skin; respiratory system; lymph node palpation; thyroid gland; left foot; right foot; left leg and right leg. The number of participants assessed as normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS) at baseline (week -2) and week 52 is presented based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week -2, week 52
,
| Intervention | Participants (Count of Participants) |
|---|
| General Appearance (week -2) Normal | General Appearance (week -2) Abnormal NCS | General Appearance (week -2) Abnormal CS | General Appearance (week 52) Normal | General Appearance (week 52) Abnormal NCS | General Appearance (week 52) Abnormal CS | Nervous System (week -2) Normal | Nervous System (week -2) Abnormal NCS | Nervous System (week -2) Abnormal CS | Nervous System (week 52) Normal | Nervous System (week 52) Abnormal NCS | Nervous System (week 52) Abnormal CS | Cardiovascular System (week-2) Normal | Cardiovascular System (week -2) Abnormal NCS | Cardiovascular System (week -2) Abnormal CS | Cardiovascular System (week52) Normal | Cardiovascular System (week 52) Abnormal NCS | Cardiovascular System (week 52) Abnormal CS | Gastrointestinal System (week -2) Normal | Gastrointestinal System (week -2) Abnormal NCS | Gastrointestinal System (week -2) Abnormal CS | Gastrointestinal System (week 52) Normal | Gastrointestinal System (week 52) Abnormal NCS | Gastrointestinal System (week 52) Abnormal CS | Skin (week -2) Normal | Skin (week -2) Abnormal NCS | Skin (week -2) Abnormal CS | Skin (week 52) Normal | Skin (week 52) Abnormal NCS | Skin (week 52) Abnormal CS | Respiratory System (week -2) Normal | Respiratory System (week -2) Abnormal NCS | Respiratory System (week -2) Abnormal CS | Respiratory System (week 52) Normal | Respiratory System (week 52) Abnormal NCS | Respiratory System (week 52) Abnormal CS | Lymph Node Palpation (week -2) Normal | Lymph Node Palpation (week -2) Abnormal NCS | Lymph Node Palpation (week -2) Abnormal CS | Lymph Node Palpation (week 52) Normal | Lymph Node Palpation (week 52) Abnormal NCS | Lymph Node Palpation (week 52) Abnormal CS | Thyroid Gland (week -2) Normal | Thyroid Gland (week -2) Abnormal NCS | Thyroid Gland (week -2) Abnormal CS | Thyroid Gland (week 52) Normal | Thyroid Gland (week 52) Abnormal NCS | Thyroid Gland (week 52) Abnormal CS | Left foot (week -2) Normal | Left foot (week -2) Abnormal NCS | Left foot (week -2) Abnormal CS | Left foot (week 52) Normal | Left foot (week 52) Abnormal NCS | Left foot (week 52) Abnormal CS | Right foot (week -2) Normal | Right foot (week -2) Abnormal NCS | Right foot (week -2) Abnormal CS | Right foot (week 52) Normal | Right foot (week 52) Abnormal NCS | Right foot (week 52) Abnormal CS | Left leg (week -2) Normal | Left leg (week -2) Abnormal NCS | Left leg (week -2) Abnormal CS | Left leg (week 52) Normal | Left leg (week 52) Abnormal NCS | Left leg (week 52) Abnormal CS | Right leg (week -2) Normal | Right leg (week -2) Abnormal NCS | Right leg (week -2) Abnormal CS | Right leg (week 52) Normal | Right leg (week 52) Abnormal NCS | Right leg (week 52) Abnormal CS |
|---|
| Canagliflozin + Semaglutide Placebo | 335 | 56 | 3 | 304 | 33 | 2 | 370 | 21 | 3 | 325 | 12 | 2 | 386 | 8 | 0 | 333 | 6 | 0 | 377 | 16 | 1 | 331 | 8 | 0 | 323 | 69 | 2 | 298 | 40 | 1 | 391 | 3 | 0 | 336 | 3 | 0 | 392 | 2 | 0 | 337 | 0 | 0 | 390 | 4 | 0 | 337 | 1 | 0 | 345 | 44 | 5 | 303 | 34 | 2 | 348 | 42 | 4 | 304 | 32 | 3 | 358 | 30 | 6 | 314 | 22 | 3 | 357 | 30 | 7 | 315 | 21 | 3 |
| Semaglutide + Canagliflozin Placebo | 345 | 46 | 1 | 294 | 30 | 2 | 360 | 26 | 5 | 303 | 21 | 2 | 376 | 15 | 1 | 318 | 7 | 1 | 369 | 22 | 1 | 319 | 7 | 0 | 330 | 62 | 0 | 286 | 39 | 1 | 383 | 7 | 2 | 321 | 4 | 1 | 390 | 1 | 0 | 325 | 0 | 0 | 390 | 2 | 0 | 326 | 0 | 0 | 343 | 47 | 2 | 293 | 32 | 1 | 344 | 45 | 3 | 289 | 34 | 3 | 348 | 40 | 4 | 300 | 22 | 4 | 350 | 37 | 5 | 301 | 19 | 6 |
Change in HbA1c
Change from baseline (week 0) to week 52 in HbA1c (glycosylated haemoglobin) was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first; and 'In-trial' observation period which started at the date of randomisation and include the period after initiation of rescue medication and/or premature trial product discontinuation, if any and ended at the last contact, withdrawal of consent or death, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Percentage (%) of HbA1c (Mean) |
|---|
| On-treatment without rescue medication | In-trial |
|---|
| Canagliflozin + Semaglutide Placebo | -1.0 | -1.0 |
| Semaglutide + Canagliflozin Placebo | -1.7 | -1.5 |
Change in Biochemistry Parameter- Total Bilirubin
Change from baseline (week 0) to week 52 in total bilirubin (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of total bilirubin (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 1.06 |
| Canagliflozin + Semaglutide Placebo | 1.13 |
Change in Biochemistry Parameter- Sodium
Change from baseline (week 0) to week 52 in sodium (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of sodium (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 1.00 |
| Canagliflozin + Semaglutide Placebo | 1.00 |
Change in Biochemistry Parameter- Potassium
Change from baseline (week 0) to week 52 in potassium (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of potassium (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 1.00 |
| Canagliflozin + Semaglutide Placebo | 1.00 |
Change in Biochemistry Parameter- Lipase
Change from baseline (week 0) to week 52 in lipase (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of lipase (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 1.25 |
| Canagliflozin + Semaglutide Placebo | 1.01 |
Change in Biochemistry Parameter- eGFR
Estimated glomerular filtration rate (eGFR) (milliliters per minute per 1.73 square meters [mL/min/1.73m^2])is calculated using the equation from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Change from baseline (week 0) to week 52 in eGFR is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of eGFR (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 0.98 |
| Canagliflozin + Semaglutide Placebo | 0.96 |
Change in Haematological Parameter- Thrombocytes
Change from baseline (week 0) to week 52 in thrombocytes (10^9 cells/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of thrombocytes (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 1.04 |
| Canagliflozin + Semaglutide Placebo | 1.00 |
Change in Biochemistry Parameter- Calcium
Change from baseline (week 0) to week 52 in calcium (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of calcium (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 1.01 |
| Canagliflozin + Semaglutide Placebo | 1.02 |
Change in Biochemistry Parameter- AST
Change from baseline (week 0) to week 52 in aspartate aminotransferase (AST) (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of AST (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 0.89 |
| Canagliflozin + Semaglutide Placebo | 0.86 |
Change in Biochemistry Parameter- Amylase
Change from baseline (week 0) to week 52 in amylase (units per liter [U/L]) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of amylase (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 1.16 |
| Canagliflozin + Semaglutide Placebo | 1.09 |
Change in ECG
The electrocardiogram (ECG) was assessed by the investigator at baseline (week 0) and week 52 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at baseline and week 52 were presented. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Participants (Count of Participants) |
|---|
| Normal (week 0) | Abnormal NCS (week 0) | Abnormal CS (week 0) | Normal (week 52) | Abnormal NCS (week 52) | Abnormal CS (week 52) |
|---|
| Canagliflozin + Semaglutide Placebo | 277 | 117 | 0 | 242 | 95 | 3 |
| Semaglutide + Canagliflozin Placebo | 263 | 126 | 3 | 222 | 109 | 0 |
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately
"Change from baseline (week 0) in DTSQ was evaluated at week 52. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of high blood sugars and low blood sugars, respectively. Thus, lower scores indicate a perception of blood glucose levels being none of the time unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the 'on-treatment without rescue medication' observation period." (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Score on a scale (Mean) |
|---|
| 1) Satisfaction with treatment | 2) Feeling of unacceptably high blood sugars | 3) Feeling of unacceptably low blood sugars | 4) Convenience of treatment | 5) Flexibility of current treatment | 6) Satisfaction with understanding of diabetes | 7) Recommending treatment to others | 8) Satisfaction to continue with present treatment | Total treatment satisfaction score |
|---|
| Canagliflozin + Semaglutide Placebo | 1.0 | -1.8 | 0.1 | 0.7 | 0.7 | 0.6 | 0.9 | 0.8 | 4.8 |
| Semaglutide + Canagliflozin Placebo | 1.4 | -2.0 | 0.1 | 0.8 | 0.8 | 0.8 | 0.9 | 1.1 | 5.8 |
Change in Control of Eating Questionnaire (CoEQ): Domains
The CoEQ comprised 19 items to assess the intensity and type of food cravings, as well as subjective sensation of appetite and mood, with the 4 domains: 'craving control', 'craving for sweet', 'craving for savoury' and 'positive mood'. The 19 items were scored on an 11-point graded response scale ranging from 10 to 0, with items relating to each of the 4 domains being averaged to create a final score. A low score in the domains 'craving for sweet and 'craving for savoury' represents a low level of craving; whereas a high score in the domains 'craving control' and 'positive mood' represents good control and a good mood, respectively. Results are based on the 'on-treatment without rescue medication' observation period. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Score on a scale (Mean) |
|---|
| Craving control | Craving for sweet | Craving for savoury | Positive mood |
|---|
| Canagliflozin + Semaglutide Placebo | 1.0 | -0.6 | -0.9 | 0.4 |
| Semaglutide + Canagliflozin Placebo | 1.0 | -0.6 | -1.1 | 0.7 |
Change in CoEQ: Individual Items
The CoEQ comprised 19 items to assess the intensity and type of food cravings, as well as subjective sensation of appetite and mood, with the 4 domains: 'craving control', 'craving for sweet', 'craving for savoury' and 'positive mood'. The 19 items were scored on an 11-point graded response scale ranging from 10 to 0, with items relating to each of the 4 domains being averaged to create a final score. A low score in the domains 'craving for sweet and 'craving for savoury' represents a low level of craving; whereas a high score in the domains 'craving control' and 'positive mood' represents good control and a good mood, respectively. Results are based on the 'on-treatment without rescue medication' observation period. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Score on a scale (Mean) |
|---|
| How hungry have you felt | How full have you felt | How often have you had cravings (last 7 days) | How strong have any cravings been | Difficulty to resist cravings | Ate in response to cravings | Difficulty to control eating | Desire to eat savory food | Craving for dairy foods | Craving for starchy foods | Craving for savory foods | Desire to eat sweet food | Craving for chocolate | Craving for other sweets | Craving for fruit or fruit juice | Felt happy | Felt anxious | Felt alert | Felt contented |
|---|
| Canagliflozin + Semaglutide Placebo | -0.8 | 0.0 | -1.1 | -1.1 | -0.8 | -0.7 | -1.2 | -1.0 | -0.6 | -1.1 | -0.9 | -1.0 | -0.4 | -0.6 | -0.6 | 0.4 | -0.6 | 0.0 | 0.5 |
| Semaglutide + Canagliflozin Placebo | -1.2 | 0.2 | -0.9 | -0.9 | -0.9 | -0.9 | -1.5 | -1.4 | -0.8 | -1.4 | -0.9 | -0.9 | -0.3 | -0.6 | -0.6 | 0.8 | -0.9 | 0.2 | 0.8 |
Total Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes
Hypoglycaemic episodes defined as treatment-emergent if the onset of the episode occurs within the on-treatment observation period. Severe or BG-confirmed symptomatic hypoglycaemia is an episode that is severe according to the American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Weeks 0-57
| Intervention | Episodes (Number) |
|---|
| Semaglutide + Canagliflozin Placebo | 25 |
| Canagliflozin + Semaglutide Placebo | 6 |
Total Number of Treatment Emergent Adverse Events (TEAEs)
A TEAE is defined as an adverse event with onset in the on-treatment observation period (which started at the date of first dose of trial product and included the period after initiation of rescue medication, if any and excluded the period after premature trial product discontinuation, if any. TEAEs assessed up to approximately 57 weeks is presented. (NCT03136484)
Timeframe: Weeks 0-57
| Intervention | Adverse events (Number) |
|---|
| Semaglutide + Canagliflozin Placebo | 1189 |
| Canagliflozin + Semaglutide Placebo | 1138 |
Percentage Change in Visceral Fat Mass (%)
Change from baseline (week 0) to week 52 in visceral fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Percentage change (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | -0.81 |
| Canagliflozin + Semaglutide Placebo | 0.16 |
Percentage Change in Total Lean Mass (%)
Change from baseline (week 0) to week 52 in total lean mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Percentage change (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 1.38 |
| Canagliflozin + Semaglutide Placebo | 1.09 |
Percentage Change in Total Fat Mass (%)
Change from baseline (week 0) to week 52 in total fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Percentage change (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | -1.55 |
| Canagliflozin + Semaglutide Placebo | -1.21 |
Eye Examination
Fundus photography or a dilated fundoscopy was performed by the investigator at baseline (week 0) and week 52. The results of the examination were interpreted for each eye (left/right) are categorised as normal, abnormal NCS or abnormal CS. Number of participants in each category at baseline and week 52 were presented. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
,
| Intervention | Participants (Count of Participants) |
|---|
| Left eye: Normal (week 0) | Left eye: Abnormal NCS (week 0) | Left eye: Abnormal CS (week 0) | Left eye: Normal (week 52) | Left eye: Abnormal NCS (week 52) | Left eye: Abnormal CS (week 52) | Right eye: Normal (week 0) | Right eye: Abnormal NCS (week 0) | Right eye: Abnormal CS (week 0) | Right eye: Normal (week 52) | Right eye: Abnormal NCS (week 52) | Right eye: Abnormal CS (week 52) |
|---|
| Canagliflozin + Semaglutide Placebo | 319 | 71 | 3 | 228 | 40 | 2 | 319 | 70 | 4 | 226 | 44 | 0 |
| Semaglutide + Canagliflozin Placebo | 322 | 65 | 5 | 231 | 30 | 7 | 321 | 66 | 5 | 225 | 35 | 8 |
Change in Biochemistry Parameter- ALT
Change from baseline (week 0) to week 52 in alanine aminotransferase (ALT) (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of ALT (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 0.79 |
| Canagliflozin + Semaglutide Placebo | 0.79 |
Change in Biochemistry Parameter- ALP
Change from baseline (week 0) to week 52 in alkaline phosphatase (ALP) (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of ALP (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 0.96 |
| Canagliflozin + Semaglutide Placebo | 0.95 |
Change in Biochemistry Parameter- Albumin
Change from baseline (week 0) to week 52 in albumin (g/dL) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of albumin (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 0.99 |
| Canagliflozin + Semaglutide Placebo | 1.00 |
Participants With Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes
Number of participants with treatment emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes. Hypoglycaemic episodes defined as treatment-emergent if the onset of the episode occurs within the on-treatment observation period. Severe or BG-confirmed symptomatic hypoglycaemia is an episode that is severe according to the American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Weeks 0-57
| Intervention | Participants (Number) |
|---|
| Semaglutide + Canagliflozin Placebo | 6 |
| Canagliflozin + Semaglutide Placebo | 5 |
Change in Waist Circumference
Change from baseline (week 0) to week 52 in waist circumference was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Centimeter (cm) (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | -4.2 |
| Canagliflozin + Semaglutide Placebo | -3.0 |
Change in Visceral Fat Mass (kg)
Change from baseline (week 0) to week 52 in visceral fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | kg (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | -0.20 |
| Canagliflozin + Semaglutide Placebo | -0.13 |
Percentage Change in Body Weight (%)
Change from baseline (week 0) to week 52 in body weight was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Percentage change (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | -6.2 |
| Canagliflozin + Semaglutide Placebo | -4.7 |
Change in Total Lean Mass (kg)
Change from baseline (week 0) to week 52 in total lean mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | kg (Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | -2.06 |
| Canagliflozin + Semaglutide Placebo | -1.53 |
Change in Biochemistry Parameter- Creatinine
Change from baseline (week 0) to week 52 in creatinine (micromoles per liter [umol/L]) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. (NCT03136484)
Timeframe: Week 0, week 52
| Intervention | Ratio of creatinine (Geometric Mean) |
|---|
| Semaglutide + Canagliflozin Placebo | 1.03 |
| Canagliflozin + Semaglutide Placebo | 1.04 |
Change From Baseline in Percentage of 2 Consecutive Glucose Readings With < 70 mg/dL
The percentage of 2 consecutive glucose readings with < 70 mg/dL were reported. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)
,
| Intervention | Percentage of readings (Mean) |
|---|
| Treatment Period 1 | Treatment Period 2 |
|---|
| Treatment Sequence AB | NA | NA |
| Treatment Sequence BA | NA | NA |
Change From Baseline in Time Spent With Glucose Level < 70 mg/dL
Time spent with the glucose level < 70 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)
,
| Intervention | Minutes (Mean) |
|---|
| Treatment Period 1 | Treatment Period 2 |
|---|
| Treatment Sequence AB | NA | NA |
| Treatment Sequence BA | NA | NA |
Change From Baseline in Time Spent With Glucose Level > 140 mg/dL
Time spent with the glucose level > 140 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)
,
| Intervention | Minutes (Mean) |
|---|
| Treatment Period 1 | Treatment Period 2 |
|---|
| Treatment Sequence AB | -231.98 | -308.68 |
| Treatment Sequence BA | -310.41 | 318.23 |
Change From Baseline in Time Spent With Glucose Level > 180 mg/dL
Time spent with the glucose level > 180 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 as per the sequence reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)
,
| Intervention | Minutes (Mean) |
|---|
| Treatment Period 1 | Treatment Period 2 |
|---|
| Treatment Sequence AB | -338.36 | -354.63 |
| Treatment Sequence BA | -305.69 | -361.65 |
Change From Baseline in Time Spent With Glucose Level 70 to 139 mg/dL
Time spent with the glucose level 70 to 139 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)
,
| Intervention | Minutes (Mean) |
|---|
| Treatment Period 1 | Treatment Period 2 |
|---|
| Treatment Sequence AB | 226.64 | 277.00 |
| Treatment Sequence BA | 275.64 | 261.57 |
Percent Change From Baseline in Time During 24 Hours With Glucose 70 to 139 mg/dL
Percent change from baseline in time during 24 hours with glucose levels 70 to 139 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)
,
| Intervention | Percent Change (Mean) |
|---|
| Treatment Period 1 | Treatment Period 2 |
|---|
| Treatment Sequence AB | 0.157 | 0.192 |
| Treatment Sequence BA | 0.191 | 0.182 |
Percent Change From Baseline in Time During 24 Hours With Glucose Greater Than (>) 140 mg/dL
Percent change from baseline in time during 24 hours within the glucose levels >140 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)
,
| Intervention | Percent Change (Mean) |
|---|
| Treatment Period 1 | Treatment Period 2 |
|---|
| Treatment Sequence AB | -0.161 | -214 |
| Treatment Sequence BA | -0.216 | -0.221 |
Percent Change From Baseline in Time During 24 Hours With Glucose Level > 180 mg/dL
Percent change from baseline in time during 24 hours within the glucose levels >180 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 as per the sequence reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)
,
| Intervention | Percent Change (Mean) |
|---|
| Treatment Period 1 | Treatment Period 2 |
|---|
| Treatment Sequence AB | -0.235 | -0.246 |
| Treatment Sequence BA | -0.212 | -0.251 |
Percent Change From Baseline in Time During 24 Hours With Glucose Level Less Than (<) 70 mg/dL
Percent change from baseline in time during 24 hours within the glucose levels < 70 mg/dL was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)
,
| Intervention | Percent Change (Mean) |
|---|
| Treatment Period 1 | Treatment Period 2 |
|---|
| Treatment Sequence AB | NA | NA |
| Treatment Sequence BA | NA | NA |
Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 1
Continuous blood glucose monitoring was done in participants using continuous glucose monitoring (CGM) determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and after each active treatment. Glucose coefficient of variation (CV) was calculated based on CGM data dividing the standard deviation of blood glucose values by the mean of the corresponding glucose readings. The participants were analyzed according to treatment received in treatment period 2 as per the sequence reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27)
| Intervention | Percentage of CV (Mean) |
|---|
| Treatment Sequence AB | -0.69 |
| Treatment Sequence BA | 0.24 |
Change From Baseline in Glycemic Coefficient of Variation (CV) in Treatment Period 2
Continuous blood glucose monitoring was done in participants using CGM determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and after each active treatment. Glucose coefficient of variation was calculated based on CGM data dividing the standard deviation of blood glucose values by the mean of the corresponding glucose readings. The participants were analyzed according to treatment received in treatment period 2 as per the sequence reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 2 (Days 66 to 71)
| Intervention | Percentage of CV (Mean) |
|---|
| Treatment Sequence AB | -1.26 |
| Treatment Sequence BA | 0.77 |
Change From Baseline in 2-hour Post-prandial Glucose (PPG) Levels
2-hour post-prandial glucose levels were determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)
,
| Intervention | mg/dL (Mean) |
|---|
| Treatment Period 1 | Treatment Period 2 |
|---|
| Treatment Sequence AB | -47.03 | -41.12 |
| Treatment Sequence BA | -43.36 | -44.03 |
Change From Baseline in Fasting Plasma Glucose Levels
Fasting plasma glucose levels were determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)
,
| Intervention | mg/dL (Mean) |
|---|
| Treatment Period 1 | Treatment Period 2 |
|---|
| Treatment Sequence AB | -32.04 | -27.69 |
| Treatment Sequence BA | -34.48 | -45.51 |
Change From Baseline in Glycemic Standard Deviation (SD) for 24-hour Glucose Profile
Glycemic standard deviation for 24-hour glucose profile (glycemic variability), as measured by CGM was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants who received the study drug in the treatment period 1 and 2 as per the sequence were reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)
,
| Intervention | mg/dL (Mean) |
|---|
| Treatment Period 1 | Treatment Period 2 |
|---|
| Treatment Sequence AB | -7.64 | -8.53 |
| Treatment Sequence BA | -8.40 | -7.13 |
Change From Baseline in Mean 24-hour Glucose Profile
Mean 24-hour glucose profiles as measured by CGM was determined over a 6-day period (in order to obtain a continuous 72-hour reading) at baseline and at the end of each active treatment. The participants were analyzed according to treatment received in treatment period 1 and treatment period 2 as per the sequence reported in this outcome measure. (NCT03267576)
Timeframe: Baseline up to End of Treatment Period 1 (Days 22 to 27) and End of Treatment Period 2 (Days 66 to 71)
,
| Intervention | mg/dL (Mean) |
|---|
| Treatment Period 1 | Treatment Period 2 |
|---|
| Treatment Sequence AB | -34.81 | -31.27 |
| Treatment Sequence BA | -39.56 | -41.74 |
Change From Baseline in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 12
Change from baseline in KCCQ-TSS was reported. KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. KCCQ-TSS was average of domains- symptom frequency and symptom burden, and transformed to a single score which ranged from 0 (worst) to 100 (the best possible status), where the higher score reflected better health status. (NCT04252287)
Timeframe: Baseline, Week 12
| Intervention | Score on a scale (Least Squares Mean) |
|---|
| Placebo | 4.9 |
| Canagliflozin 100 mg | 9.2 |
Change From Baseline in KCCQ Clinical Summary Score at Week 12
Change from baseline in KCCQ-clinical summary score was reported. KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. KCCQ-clinical summary score was average of domains- physical limitation and total symptoms (average of symptom frequency and symptom burden), and transformed to a single score which ranged from 0 (worst) -100 (the best possible status), where the higher score reflected better health status. (NCT04252287)
Timeframe: Baseline, Week 12
| Intervention | Score on a scale (Least Squares Mean) |
|---|
| Placebo | 4.7 |
| Canagliflozin 100 mg | 8.5 |
Change From Baseline in KCCQ Overall Summary Score at Week 12
Change from baseline in KCCQ-overall summary score was reported. KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. KCCQ- overall summary score was average of domains- physical limitation, total symptoms (average of symptom frequency and symptom burden), quality of life, and social limitation, and transformed to a single score which ranged from 0 (worst) -100 (the best possible status), where the higher score reflected better health status. (NCT04252287)
Timeframe: Baseline, Week 12
| Intervention | Score on a scale (Least Squares Mean) |
|---|
| Placebo | 6.2 |
| Canagliflozin 100 mg | 9.5 |
Change From Baseline in Total Daily Step Count at Week 12
Change from baseline in total daily step count at Week 12 was reported in this outcome measure. The number of steps taken per day was measured using a step activity monitor at baseline and throughout the study. Step count was measured from the Fitbit device data. The Fitbit app on the participant's phone collected all data from the Fitbit device. A negative change from baseline indicated a decrease in the number of daily steps. (NCT04252287)
Timeframe: Baseline, Week 12
| Intervention | Daily step count (Least Squares Mean) |
|---|
| Placebo | -74.9 |
| Canagliflozin 100 mg | -45.1 |
Change From Baseline in KCCQ Individual Domain Scores (Physical Limitation and Quality of Life) at Week 12
Change from baseline in KCCQ physical limitation score and KCCQ quality of life score were reported. KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 (worst) and 100 (the best possible status), where the higher score reflected better health status. (NCT04252287)
Timeframe: Baseline, Week 12
,
| Intervention | Score on a scale (Least Squares Mean) |
|---|
| KCCQ-Physical Limitation | KCCQ-Quality of Life |
|---|
| Canagliflozin 100 mg | 7.8 | 12.4 |
| Placebo | 4.8 | 9.1 |
Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24
Percent change from baseline in HbA1c at Weeks 12 and 24 was reported. (NCT04288778)
Timeframe: Baseline, Weeks 12 and 24
| Intervention | Percent change (Mean) |
|---|
| Percent change at Week 12 | Percent change at Week 24 |
|---|
| Canagliflozin + Metformin Hydrochloride FDC | -0.918 | -0.926 |
Percentage of Participants With Unexpected Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An adverse event was considered unexpected if the nature or severity was not consistent with the applicable product reference safety information. (NCT04288778)
Timeframe: Baseline (Day 1) up to 24 weeks
| Intervention | Percentage of participants (Number) |
|---|
| Canagliflozin + Metformin Hydrochloride FDC | 0 |
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was any untoward medical occurrence that at any dose resulted in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product. TEAEs were defined as events that started on or after the study medication start date and time. (NCT04288778)
Timeframe: Baseline (Day 1) up to 24 weeks
| Intervention | Percentage of participants (Number) |
|---|
| TEAEs | TESAEs |
|---|
| Canagliflozin + Metformin Hydrochloride FDC | 41.6 | 1.1 |
Percentage of Participants With Adverse Drug Reactions (ADRs)
ADRs were defined as the treatment related TEAEs. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAEs were defined as events that started on or after the study medication start date and time. (NCT04288778)
Timeframe: Baseline (Day 1) up to 24 weeks
| Intervention | Percentage of participants (Number) |
|---|
| Canagliflozin + Metformin Hydrochloride FDC | 10.6 |