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The CANTATA-MP Trial (CANagliflozin Treatment and Trial Analysis - Metformin and Pioglitazone)

Primary Purpose

Diabetes Mellitus, Type 2

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
Canagliflozin
Sitagliptin
Metformin
Pioglitazone
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring Canagliflozin, Placebo, Sitagliptin (Januvia), Metformin, Pioglitazone (Actos), Hemoglobin A1c, Type 2 diabetes mellitus

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • All patients must have a diagnosis of T2DM and be currently treated with PPAR gamma agent ((pioglitazone or rosiglitazone) and another anti-diabetes agent (metformin)
  • Patients in the study must have a HbA1c between >=7 and <=10.5% and a fasting plasma glucose (FPG) <270 mg/dL (15 mmol/L)

Exclusion Criteria:

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Experimental

Experimental

Arm Label

Placebo/Sitagliptin

Canagliflozin 100 mg

Canagliflozin 300 mg

Arm Description

Each patient will receive matching placebo once daily for 26 weeks with stable doses of metformin and pioglitazone. At Week 26, patients will be switched from placebo to 100 mg of sitagliptin once daily with stable doses of metformin and pioglitazone until Week 52.

Each patient will receive 100 mg of canagliflozin once daily for 52 weeks with stable doses of metformin and pioglitazone.

Each patient will receive 300 mg of canagliflozin once daily for 52 weeks with stable doses of metformin and pioglitazone.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
April 1, 2010
Last Updated
June 26, 2013
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01106690
Brief Title
The CANTATA-MP Trial (CANagliflozin Treatment and Trial Analysis - Metformin and Pioglitazone)
Official Title
A Randomized, Double-Blind, Placebo-Controlled, 3-Arm, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin in the Treatment of Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin and Pioglitazone Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to evaluate the efficacy and safety of 2 different doses of canagliflozin compared with placebo in patients with type 2 diabetes mellitus who are receving treatment with metformin and pioglitazone and have inadequate glycemic (blood sugar) control.
Detailed Description
Canagliflozin is a drug that is being tested to see if it may be useful in treating patients diagnosed with type 2 diabetes mellitus (T2DM). This is a randomized (study drug assigned by chance), double-blind (neither the patient or the study doctor will know the name of the assigned treatment), parallel-group, 3-arm (3 treatment groups) multicenter study to determine the efficacy, safety, and tolerability of canagliflozin (100 mg and 300 mg) compared to placebo (a capsule that looks like all the other treatments but has no real medicine) in patients with T2DM who are not achieving an adequate response from current antihyperglycemic therapy with metformin and pioglitazone to control their diabetes. Approximately 360 patients with T2DM who are receiving combination therapy with metformin and pioglitazone will receive the addition of once-daily treatment with canagliflozin (100 mg or 300 mg) or placebo capsules for 26 weeks followed by a 26-week extension period where patients treated with canagliflozin (100 mg or 300 mg) will continue treatment for an additional 26 weeks and patients treated with placebo will be switched to active double-blind treatment with sitagliptin 100 mg, an antihyperglycemic agent administered once-daily for 26 weeks. In addition, all patients will take protocol specified stable doses of metformin and pioglitazone along with assigned study drug for the duration of the study. Patients will participate in the study for approximately 59 to 78 weeks. During the study, if a patient's fasting blood sugar remains high despite treatment with study drug, the patient will receive treatment with glimepiride (rescue therapy) in accordance with local prescribing information. During treatment, patients will be monitored for safety by review of adverse events, results from laboratory tests, 12-lead electrocardiograms (ECGs), vital signs measurements, body weight, physical examinations, and self-monitored blood glucose (SMGB) measurements. The primary outcome measure in the study is the effect of canagliflozin relative to placebo on hemoglobin A1c (HbA1c) after 26 weeks of treatment. Study drug will be taken orally (by mouth) once daily before the first meal each day unless otherwise specified. Patients will take single-blind placebo capsules for 2 weeks before randomization. After randomization, patients will take double-blind canagliflozin (100 mg or 300 mg) for 52 weeks OR placebo for 26 weeks switched to double-blind sitagliptin 100 mg for 26 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
Canagliflozin, Placebo, Sitagliptin (Januvia), Metformin, Pioglitazone (Actos), Hemoglobin A1c, Type 2 diabetes mellitus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
344 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo/Sitagliptin
Arm Type
Other
Arm Description
Each patient will receive matching placebo once daily for 26 weeks with stable doses of metformin and pioglitazone. At Week 26, patients will be switched from placebo to 100 mg of sitagliptin once daily with stable doses of metformin and pioglitazone until Week 52.
Arm Title
Canagliflozin 100 mg
Arm Type
Experimental
Arm Description
Each patient will receive 100 mg of canagliflozin once daily for 52 weeks with stable doses of metformin and pioglitazone.
Arm Title
Canagliflozin 300 mg
Arm Type
Experimental
Arm Description
Each patient will receive 300 mg of canagliflozin once daily for 52 weeks with stable doses of metformin and pioglitazone.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
One matching placebo capsule orally (by mouth) once daily for 26 weeks with stable doses of metformin and pioglitazone.
Intervention Type
Drug
Intervention Name(s)
Canagliflozin
Intervention Description
One 100 mg or 300 mg over-encapsulated tablet orally once daily for 52 weeks with stable doses of metformin and pioglitazone.
Intervention Type
Drug
Intervention Name(s)
Sitagliptin
Intervention Description
One 100 mg over-encapsulated tablet orally once daily beginning at Week 26 until Week 52 with stable doses of metformin and pioglitazone.
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
The patient's stable dose of metformin background therapy should be continued throughout the study.
Intervention Type
Drug
Intervention Name(s)
Pioglitazone
Intervention Description
The patient's stable dose of pioglitazone background therapy should be continued throughout the study.
Primary Outcome Measure Information:
Title
Change in HbA1c From Baseline to Week 26
Description
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
Time Frame
Day 1 (Baseline) and Week 26
Secondary Outcome Measure Information:
Title
Percentage of Patients With HbA1c <7% at Week 26
Description
The table below shows the percentage of patients with HbA1c<7% at Week 26 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.
Time Frame
Week 26
Title
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26
Description
The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
Time Frame
Day 1 (Baseline) and Week 26
Title
Change in Homeostasis Model Assessment (HOMA2-%B) From Baseline to Week 26
Description
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.
Time Frame
Day 1 (Baseline) and Week 26
Title
Percent Change in Body Weight From Baseline to Week 26
Description
The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.
Time Frame
Day 1 (Baseline) and Week 26
Title
Change in Systolic Blood Pressure (SBP) From Baseline to Week 26
Description
The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
Time Frame
Day 1 (Baseline) and Week 26
Title
Percent Change in Triglycerides From Baseline to Week 26
Description
The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.
Time Frame
Day 1 (Baseline) and Week 26
Title
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
Description
The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.
Time Frame
Day 1 (Baseline) and Week 26

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All patients must have a diagnosis of T2DM and be currently treated with PPAR gamma agent ((pioglitazone or rosiglitazone) and another anti-diabetes agent (metformin) Patients in the study must have a HbA1c between >=7 and <=10.5% and a fasting plasma glucose (FPG) <270 mg/dL (15 mmol/L) Exclusion Criteria: History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy or a severe hypoglycemic episode within 6 months before screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC C. Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Anniston
State/Province
Alabama
Country
United States
City
Phoenix
State/Province
Arizona
Country
United States
City
Tucson
State/Province
Arizona
Country
United States
City
Little Rock
State/Province
Arkansas
Country
United States
City
Burlingame
State/Province
California
Country
United States
City
Encinitas
State/Province
California
Country
United States
City
Fullerton
State/Province
California
Country
United States
City
Roseville
State/Province
California
Country
United States
City
Santa Ana
State/Province
California
Country
United States
City
Wes Hills
State/Province
California
Country
United States
City
Colorado Springs
State/Province
Colorado
Country
United States
City
Bartow
State/Province
Florida
Country
United States
City
Hollywood
State/Province
Florida
Country
United States
City
Jacksonville
State/Province
Florida
Country
United States
City
Pembroke Pines
State/Province
Florida
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United States
City
Des Moines
State/Province
Iowa
Country
United States
City
Baton Rouge
State/Province
Louisiana
Country
United States
City
Chaska
State/Province
Minnesota
Country
United States
City
Picayune
State/Province
Mississippi
Country
United States
City
Billings
State/Province
Montana
Country
United States
City
Charlotte
State/Province
North Carolina
Country
United States
City
Hickory
State/Province
North Carolina
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United States
City
Raleigh
State/Province
North Carolina
Country
United States
City
Dublin
State/Province
Ohio
Country
United States
City
Perrysburg
State/Province
Ohio
Country
United States
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Tulsa
State/Province
Oklahoma
Country
United States
City
Yukon
State/Province
Oklahoma
Country
United States
City
Bensalem
State/Province
Pennsylvania
Country
United States
City
Bristol
State/Province
Tennessee
Country
United States
City
Kingsport
State/Province
Tennessee
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Nashville
State/Province
Tennessee
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United States
City
Arlington
State/Province
Texas
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Grand Prairie
State/Province
Texas
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United States
City
Houston
State/Province
Texas
Country
United States
City
New Braunfels
State/Province
Texas
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
Falls Church
State/Province
Virginia
Country
United States
City
Virginia Beach
State/Province
Virginia
Country
United States
City
Federal Way
State/Province
Washington
Country
United States
City
Selah
State/Province
Washington
Country
United States
City
Bathurst
State/Province
New Brunswick
Country
Canada
City
Moncton
State/Province
New Brunswick
Country
Canada
City
Grand Falls-Windsor
State/Province
Newfoundland and Labrador
Country
Canada
City
Brampton
State/Province
Ontario
Country
Canada
City
Hamilton
State/Province
Ontario
Country
Canada
City
Ottawa
State/Province
Ontario
Country
Canada
City
Smiths Falls
State/Province
Ontario
Country
Canada
City
Thornhill
State/Province
Ontario
Country
Canada
City
Drummondville
State/Province
Quebec
Country
Canada
City
Calgary
Country
Canada
City
Mount Pearl
Country
Canada
City
Truro
Country
Canada
City
Kuopio
Country
Finland
City
Oulu
Country
Finland
City
Turku
Country
Finland
City
Bondy Cedex
Country
France
City
Le Creusot
Country
France
City
Narbonne Cedex
Country
France
City
Aschaffenburg
Country
Germany
City
Mainz
Country
Germany
City
Neuwied
Country
Germany
City
Schkeuditz
Country
Germany
City
Athens
Country
Greece
City
Thessalonikis
Country
Greece
City
Thessaloniki
Country
Greece
City
Ahmedabad
Country
India
City
Belgaum
Country
India
City
Chennai
Country
India
City
Coimbatore
Country
India
City
Jaipur
Country
India
City
Nagpur
Country
India
City
Chihuahua
Country
Mexico
City
Ciudad Juarez
Country
Mexico
City
Durango
Country
Mexico
City
Mexico
Country
Mexico
City
Almería
Country
Spain
City
Madrid
Country
Spain
City
Sevilla
Country
Spain
City
Bangkok
Country
Thailand
City
Khon Kaen
Country
Thailand
City
Antrim
Country
United Kingdom
City
Belfast
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
28327140
Citation
Davies MJ, Merton K, Vijapurkar U, Yee J, Qiu R. Efficacy and safety of canagliflozin in patients with type 2 diabetes based on history of cardiovascular disease or cardiovascular risk factors: a post hoc analysis of pooled data. Cardiovasc Diabetol. 2017 Mar 21;16(1):40. doi: 10.1186/s12933-017-0517-7.
Results Reference
derived
PubMed Identifier
28241822
Citation
Pfeifer M, Townsend RR, Davies MJ, Vijapurkar U, Ren J. Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure and markers of arterial stiffness in patients with type 2 diabetes mellitus: a post hoc analysis. Cardiovasc Diabetol. 2017 Feb 27;16(1):29. doi: 10.1186/s12933-017-0511-0.
Results Reference
derived
PubMed Identifier
28197834
Citation
Gilbert RE, Mende C, Vijapurkar U, Sha S, Davies MJ, Desai M. Effects of Canagliflozin on Serum Magnesium in Patients With Type 2 Diabetes Mellitus: A Post Hoc Analysis of Randomized Controlled Trials. Diabetes Ther. 2017 Apr;8(2):451-458. doi: 10.1007/s13300-017-0232-0. Epub 2017 Feb 14.
Results Reference
derived
PubMed Identifier
27977934
Citation
Qiu R, Balis D, Xie J, Davies MJ, Desai M, Meininger G. Longer-term safety and tolerability of canagliflozin in patients with type 2 diabetes: a pooled analysis. Curr Med Res Opin. 2017 Mar;33(3):553-562. doi: 10.1080/03007995.2016.1271780. Epub 2017 Jan 4.
Results Reference
derived
PubMed Identifier
27600862
Citation
John M, Cerdas S, Violante R, Deerochanawong C, Hassanein M, Slee A, Canovatchel W, Hamilton G. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus living in hot climates. Int J Clin Pract. 2016 Sep;70(9):775-85. doi: 10.1111/ijcp.12868.
Results Reference
derived
PubMed Identifier
26580237
Citation
Watts NB, Bilezikian JP, Usiskin K, Edwards R, Desai M, Law G, Meininger G. Effects of Canagliflozin on Fracture Risk in Patients With Type 2 Diabetes Mellitus. J Clin Endocrinol Metab. 2016 Jan;101(1):157-66. doi: 10.1210/jc.2015-3167. Epub 2015 Nov 18.
Results Reference
derived
PubMed Identifier
26373629
Citation
Blonde L, Woo V, Mathieu C, Yee J, Vijapurkar U, Canovatchel W, Meininger G. Achievement of treatment goals with canagliflozin in patients with type 2 diabetes mellitus: a pooled analysis of randomized controlled trials. Curr Med Res Opin. 2015 Nov;31(11):1993-2000. doi: 10.1185/03007995.2015.1082991. Epub 2015 Sep 28.
Results Reference
derived
PubMed Identifier
26121561
Citation
Gavin JR 3rd, Davies MJ, Davies M, Vijapurkar U, Alba M, Meininger G. The efficacy and safety of canagliflozin across racial groups in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2015;31(9):1693-702. doi: 10.1185/03007995.2015.1067192. Epub 2015 Sep 4.
Results Reference
derived
PubMed Identifier
25813214
Citation
Cefalu WT, Stenlof K, Leiter LA, Wilding JP, Blonde L, Polidori D, Xie J, Sullivan D, Usiskin K, Canovatchel W, Meininger G. Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes. Diabetologia. 2015 Jun;58(6):1183-7. doi: 10.1007/s00125-015-3547-2. Epub 2015 Mar 27.
Results Reference
derived
PubMed Identifier
25329038
Citation
Weir MR, Januszewicz A, Gilbert RE, Vijapurkar U, Kline I, Fung A, Meininger G. Effect of canagliflozin on blood pressure and adverse events related to osmotic diuresis and reduced intravascular volume in patients with type 2 diabetes mellitus. J Clin Hypertens (Greenwich). 2014 Dec;16(12):875-82. doi: 10.1111/jch.12425. Epub 2014 Oct 20.
Results Reference
derived
PubMed Identifier
24918789
Citation
Usiskin K, Kline I, Fung A, Mayer C, Meininger G. Safety and tolerability of canagliflozin in patients with type 2 diabetes mellitus: pooled analysis of phase 3 study results. Postgrad Med. 2014 May;126(3):16-34. doi: 10.3810/pgm.2014.05.2753.
Results Reference
derived
PubMed Identifier
24786834
Citation
Weir MR, Kline I, Xie J, Edwards R, Usiskin K. Effect of canagliflozin on serum electrolytes in patients with type 2 diabetes in relation to estimated glomerular filtration rate (eGFR). Curr Med Res Opin. 2014 Sep;30(9):1759-68. doi: 10.1185/03007995.2014.919907. Epub 2014 May 22.
Results Reference
derived
PubMed Identifier
24742013
Citation
Sinclair A, Bode B, Harris S, Vijapurkar U, Mayer C, Fung A, Shaw W, Usiskin K, Desai M, Meininger G. Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. BMC Endocr Disord. 2014 Apr 18;14:37. doi: 10.1186/1472-6823-14-37.
Results Reference
derived
PubMed Identifier
24517339
Citation
Nyirjesy P, Sobel JD, Fung A, Mayer C, Capuano G, Ways K, Usiskin K. Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. Curr Med Res Opin. 2014 Jun;30(6):1109-19. doi: 10.1185/03007995.2014.890925. Epub 2014 Feb 21.
Results Reference
derived

Learn more about this trial

The CANTATA-MP Trial (CANagliflozin Treatment and Trial Analysis - Metformin and Pioglitazone)

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