CANagliflozin Treatment And Trial Analysis-Sulfonylurea (CANTATA-SU) SGLT2 Add-on to Metformin Versus Glimepiride

NCT ID: NCT00968812

Last Updated: 2017-01-30

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1452 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-09-30

Study Completion Date

2013-01-31

Brief Summary

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The purpose of this study is to demonstrate the efficacy, safety, and tolerability of canagliflozin (JNJ-28431754) compared with glimepiride in patients with type 2 diabetes mellitus with inadequate control despite treatment with metformin.

Detailed Description

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Type 2 diabetes mellitus (T2DM) is well recognized as a major public health problem that presents patients with a significant risk of complications including heart disease, retinopathy, nephropathy, and neuropathy. Various classes of orally administered antihyperglycemic agents have been developed for the treatment of diabetes and although individual agents may be highly effective for some patients, it is still difficult to maintain optimal glycemic control in most patients, thereby resulting in high rates of morbidity and mortality in the diabetic population. This is a randomized, double-blind, active comparator-controlled, 3-arm, parallel-group, multicenter study to demonstrate the efficacy, safety, and tolerability of canagliflozin compared with a sulfonylurea (glimepiride) in patients with T2DM, 18 to 80 years of age, inclusive, who are not optimally controlled on metformin monotherapy. The primary study hypothesis is that the study drug will be non-inferior to glimepiride as assessed by the change in hemoglobin A1c (HbA1c) from baseline. The patients will receive capsules taken by mouth of canagliflozin (either 100 or 300 mg), or glimepiride with a starting dosage of 1 mg, which will be increased to a maximum dose of 6 or 8 mg once daily for a total duration of 104 weeks.

Conditions

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Diabetes Mellitus, Type 2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Glimepiride

Each patient will receive glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks.

Group Type ACTIVE_COMPARATOR

Glimepiride

Intervention Type DRUG

Glimepiride will be given orally (by mouth), as over-encapsulated tablets, starting at a dose of 1mg once daily and increasing to a maximum of 6 mg or 8 mg once daily for 104 weeks.

Metformin

Intervention Type DRUG

Metformin will be given orally at the protocol-specified dose for 104 weeks.

Canagliflozin 100 mg

Each patient will receive 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.

Group Type EXPERIMENTAL

Canagliflozin (JNJ-28431754)

Intervention Type DRUG

Canagliflozin (JNJ-28431754) will be given orally as over-encapsulated tablets, at a dose of 100 mg or 300 mg once daily for 104 weeks.

Metformin

Intervention Type DRUG

Metformin will be given orally at the protocol-specified dose for 104 weeks.

Canagliflozin 300 mg

Each volunteer will receive 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.

Group Type EXPERIMENTAL

Canagliflozin (JNJ-28431754)

Intervention Type DRUG

Canagliflozin (JNJ-28431754) will be given orally as over-encapsulated tablets, at a dose of 100 mg or 300 mg once daily for 104 weeks.

Metformin

Intervention Type DRUG

Metformin will be given orally at the protocol-specified dose for 104 weeks.

Interventions

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Glimepiride

Glimepiride will be given orally (by mouth), as over-encapsulated tablets, starting at a dose of 1mg once daily and increasing to a maximum of 6 mg or 8 mg once daily for 104 weeks.

Intervention Type DRUG

Canagliflozin (JNJ-28431754)

Canagliflozin (JNJ-28431754) will be given orally as over-encapsulated tablets, at a dose of 100 mg or 300 mg once daily for 104 weeks.

Intervention Type DRUG

Metformin

Metformin will be given orally at the protocol-specified dose for 104 weeks.

Intervention Type DRUG

Other Intervention Names

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sulfonylurea

Eligibility Criteria

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Inclusion Criteria

* Patients must have a diagnosis of type 2 diabetes
* Body mass index (BMI) \>=22 to \<=45 kg/m2, at screening
* Patients must be taking a stable dosage of metformin as monotherapy at screening
* Patients must have a HbA1c between \>=7% and \<=9.5% at Week 2
* Patients must have a fasting plasma glucose (FPG) \<=270 mg/dL (15 mmol/L) at Week -2

Exclusion Criteria

* Patients having prior exposure or known contraindication or suspected hypersensitivity to JNJ-28431754, glimepiride, or metformin
* History of diabetic ketoacidosis or type 1 diabetes mellitus
* History of pancreas or beta-cell transplantation
* History of active proliferative diabetic retinopathy
* History of hereditary glucose-galactose malabsorption or primary renal glucosuria
* Renal disease requiring treatment with immunosuppressive therapy within the past 12 months before screening or a history of dialysis or renal transplant
* Taken thiazolidinedione therapy in the past 16 weeks before screening
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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Calera, Alabama, United States

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Gilbert, Arizona, United States

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Mesa, Arizona, United States

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Tucson, Arizona, United States

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Jonesboro, Arkansas, United States

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Buena Park, California, United States

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Encinitas, California, United States

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Fresno, California, United States

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Lincoln, California, United States

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Roseville, California, United States

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San Diego, California, United States

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Westlake Village, California, United States

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Chipley, Florida, United States

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Marianna, Florida, United States

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Oldsmar, Florida, United States

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Orlando, Florida, United States

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Augusta, Georgia, United States

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Perry, Georgia, United States

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Nampa, Idaho, United States

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Chicago, Illinois, United States

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Vernon Hills, Illinois, United States

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Valparaiso, Indiana, United States

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New Orleans, Louisiana, United States

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Elkridge, Maryland, United States

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Bloomfield Hills, Michigan, United States

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Las Vegas, Nevada, United States

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Canal Fulton, Ohio, United States

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Gallipolis, Ohio, United States

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Mason, Ohio, United States

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Perrysburg, Ohio, United States

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Tulsa, Oklahoma, United States

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Yukon, Oklahoma, United States

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Fleetwood, Pennsylvania, United States

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Greenville, South Carolina, United States

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Nashville, Tennessee, United States

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Houston, Texas, United States

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Odessa, Texas, United States

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Pearland, Texas, United States

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San Antonio, Texas, United States

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Danville, Virginia, United States

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Olympia, Washington, United States

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Milwaukee, Wisconsin, United States

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Wauwatosa, Wisconsin, United States

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Buenos Aires, , Argentina

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Mar del Plata, , Argentina

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Rosario, , Argentina

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Dimitrovgrad, , Bulgaria

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Kazanlak, , Bulgaria

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Rousse, , Bulgaria

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Sofia, , Bulgaria

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Chilliwack, British Columbia, Canada

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Kelowna, British Columbia, Canada

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Vancouver, British Columbia, Canada

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St. John's, Newfoundland and Labrador, Canada

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Mississauga, Ontario, Canada

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Toronto, Ontario, Canada

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Québec, Quebec, Canada

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Saskatoon, Saskatchewan, Canada

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San José, , Costa Rica

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San Pedro, , Costa Rica

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Aalborg, , Denmark

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Ballerup Municipality, , Denmark

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Vejle, , Denmark

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Vipperoed, , Denmark

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Helsinki, , Finland

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Kokkola, , Finland

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Kuopio, , Finland

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Oulu, , Finland

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Turku, , Finland

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Berlin, , Germany

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Dresden, , Germany

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Düsseldorf, , Germany

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Hamburg, , Germany

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Mainz, , Germany

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Villingen-Schwenningen, , Germany

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Bangalore, , India

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Chennai, , India

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Coimbatore, , India

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Hyderabad, , India

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Nagpur, , India

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Pune, , India

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Wardha, , India

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Beersheba, , Israel

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Haifa, , Israel

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Holon, , Israel

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Jerusalem, , Israel

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Ramat Gan, , Israel

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Rehovot, , Israel

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Safed, , Israel

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Tel Aviv, , Israel

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Mexico City, , Mexico

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México, , Mexico

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Monterrey, , Mexico

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Ålesund, , Norway

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Oslo, , Norway

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Cebu, , Philippines

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Marikina City, , Philippines

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Pasay, , Philippines

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Quezon City, , Philippines

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Bydgoszcz, , Poland

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Krakow, , Poland

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Kutno, , Poland

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Lodz, , Poland

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Lublin, , Poland

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Torun, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Zielona Góra, , Poland

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Ponce, , Puerto Rico

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Baia Mare, , Romania

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Brasov, , Romania

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Bucharest, , Romania

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Cluj-Napoca, , Romania

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Galati, , Romania

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Ploieşti, , Romania

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Târgu Mureş, , Romania

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Arkhangelsk, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Samara, , Russia

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Saratov, , Russia

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Banská Bystrica, , Slovakia

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Bratislava, , Slovakia

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Ľubochňa, , Slovakia

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Prešov, , Slovakia

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Daegu, , South Korea

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Goyang-si, , South Korea

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Gyeonggi-do, , South Korea

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Incheon, , South Korea

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Seoul, , South Korea

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Suwon, , South Korea

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Wŏnju, , South Korea

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Dnipro, , Ukraine

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Kharkiv, , Ukraine

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Kiev, , Ukraine

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Poltava, , Ukraine

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Ternopil, , Ukraine

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Vinnitsa, , Ukraine

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Countries

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United States Argentina Bulgaria Canada Costa Rica Denmark Finland Germany India Israel Mexico Norway Philippines Poland Puerto Rico Romania Russia Slovakia South Korea Ukraine

References

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Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

Reference Type DERIVED
PMID: 38770818 (View on PubMed)

Heerspink HJL, Perco P, Mulder S, Leierer J, Hansen MK, Heinzel A, Mayer G. Canagliflozin reduces inflammation and fibrosis biomarkers: a potential mechanism of action for beneficial effects of SGLT2 inhibitors in diabetic kidney disease. Diabetologia. 2019 Jul;62(7):1154-1166. doi: 10.1007/s00125-019-4859-4. Epub 2019 Apr 17.

Reference Type DERIVED
PMID: 31001673 (View on PubMed)

Garvey WT, Van Gaal L, Leiter LA, Vijapurkar U, List J, Cuddihy R, Ren J, Davies MJ. Effects of canagliflozin versus glimepiride on adipokines and inflammatory biomarkers in type 2 diabetes. Metabolism. 2018 Aug;85:32-37. doi: 10.1016/j.metabol.2018.02.002. Epub 2018 Feb 13.

Reference Type DERIVED
PMID: 29452178 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27977934 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27600862 (View on PubMed)

Patel CA, Bailey RA, Vijapurkar U, Meininger G, Blonde L. A post-hoc analysis of the comparative efficacy of canagliflozin and glimepiride in the attainment of type 2 diabetes-related quality measures. BMC Health Serv Res. 2016 Aug 5;16(a):356. doi: 10.1186/s12913-016-1607-z.

Reference Type DERIVED
PMID: 27495291 (View on PubMed)

Blonde L, Stenlof K, Fung A, Xie J, Canovatchel W, Meininger G. Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks. Postgrad Med. 2016 May;128(4):371-80. doi: 10.1080/00325481.2016.1169894. Epub 2016 Apr 7.

Reference Type DERIVED
PMID: 27002421 (View on PubMed)

Leiter LA, Langslet G, Vijapurkar U, Davies MJ, Canovatchel W. Simultaneous Reduction in Both HbA1c and Body Weight with Canagliflozin Versus Glimepiride in Patients with Type 2 Diabetes on Metformin. Diabetes Ther. 2016 Jun;7(2):269-78. doi: 10.1007/s13300-016-0163-1. Epub 2016 Mar 16.

Reference Type DERIVED
PMID: 26984361 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26580237 (View on PubMed)

Lavalle-Gonzalez FJ, Eliaschewitz FG, Cerdas S, Chacon Mdel P, Tong C, Alba M. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America. Curr Med Res Opin. 2016;32(3):427-39. doi: 10.1185/03007995.2015.1121865. Epub 2016 Jan 14.

Reference Type DERIVED
PMID: 26579834 (View on PubMed)

Leiter LA, Yoon KH, Arias P, Langslet G, Xie J, Balis DA, Millington D, Vercruysse F, Canovatchel W, Meininger G. Canagliflozin provides durable glycemic improvements and body weight reduction over 104 weeks versus glimepiride in patients with type 2 diabetes on metformin: a randomized, double-blind, phase 3 study. Diabetes Care. 2015 Mar;38(3):355-64. doi: 10.2337/dc13-2762. Epub 2014 Sep 9.

Reference Type DERIVED
PMID: 25205142 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24517339 (View on PubMed)

Cefalu WT, Leiter LA, Yoon KH, Arias P, Niskanen L, Xie J, Balis DA, Canovatchel W, Meininger G. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet. 2013 Sep 14;382(9896):941-50. doi: 10.1016/S0140-6736(13)60683-2. Epub 2013 Jul 12.

Reference Type DERIVED
PMID: 23850055 (View on PubMed)

Other Identifiers

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28431754DIA3009

Identifier Type: OTHER

Identifier Source: secondary_id

2009-009320-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR016480

Identifier Type: -

Identifier Source: org_study_id

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