A Study for Comparison of Canagliflozin Versus Alternative Antihyperglycemic Treatments on Risk of Heart Failure Hospitalization and Amputation for Participants With Type 2 Diabetes Mellitus and the Subpopulation With Established Cardiovascular Disease

Comparison of Canagliflozin vs. Alternative Antihyperglycemic Treatments on Risk of Heart Failure Hospitalization and Amputation for Patients With Type 2 Diabetes Mellitus and the Subpopulation With Established Cardiovascular Disease

The primary purpose of study is to estimate the incidence and comparative effect on health outcomes: 1) hospitalization for heart failure, 2) below knee lower extremity amputation. The date of first exposure to the particular drug(s) in the database, where the exposure start is between 1-April-2013 to 15-May-2017 and outcome data for these participants will be analyzed and reported in this study.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Canagliflozin; Drug: Empagliflozin; Drug: Dapagliflozin; Drug: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors; Drug: Glucagon-like Peptide-1 (GLP-1) Agonist; Drug: Anti-hyperglycemic Agents (AHA); Drug: Thiazolidinediones (TZD); Drug: Sulfonylureas (SU); Drug: Insulin

• Study Type: Observational
• Enrollment (Actual): 714582

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Titusville, New Jersey, United States, 08560
      • Janssen Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants diagnosed with type 2 diabetes mellitus (T2DM) and established cardiovascular (CV) disease over a 4-year period 1 April 2013 and 15 May 2017 will be observed.

Description

Inclusion Criteria:

• First exposure to the particular drug(s) in database (index date)
• Exposure start is between 1 April 2013 and 15 May 2017
• At least 365 days of continuous observation time prior to index
• At least 1 condition occurrence of 'Type II diabetes' any time in the prior continuous observation time (which is at least 365 days long) before or on the index date (first exposure to the particular drug(s) in database)

For cohort with 'established cardiovascular disease - At least 1 occurrence of 'conditions indicating established cardiovascular disease' on or any time in the prior continuous observation time (which is at least 365 days long) prior to the index date

Exclusion Criteria:

- Participants with type 1 diabetes or secondary diabetes prior to or on the index date of exposure were excluded from the study

Study Plan

How is the study designed?

Number of groups / cohorts

12

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1: Canagliflozin; A target cohort which includes new users of canagliflozin for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. Truven Health MarketScan Commercial Claims and Encounters Database (CCAE) 2. Truven Health MarketScan Medicare Supplemental and Coordination of Benefits Database (MDCR) 3. Truven Health MarketScan Multi-state Medicaid Database (MDCD) 4. OptumInsight's de-identified Clinformatics Datamart, Extended-Date of Death (Optum).	Drug: Canagliflozin; No intervention or treatment assignment imposed by this study. Participants received canagliflozin as a part of routine clinical practice.
Cohort 2: Canagliflozin with Cardiovascular Disease (CVD); A target cohort which includes new users of canagliflozin with established CVD for clinical characterization and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Canagliflozin; No intervention or treatment assignment imposed by this study. Participants received canagliflozin as a part of routine clinical practice.
Cohort 3: Empagliflozin; A comparator cohort which includes new users of empagliflozin for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Empagliflozin; No intervention or treatment assignment imposed by this study. Participants received empagliflozin as a part of routine clinical practice.
Cohort 4: Empagliflozin with CVD; A comparator cohort which includes new users of empagliflozin with established CVD for clinical characterization and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Empagliflozin; No intervention or treatment assignment imposed by this study. Participants received empagliflozin as a part of routine clinical practice.
Cohort 5: Dapagliflozin; A comparator cohort which includes new users of dapagliflozin for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Dapagliflozin; No intervention or treatment assignment imposed by this study. Participants received dapagliflozin as a part of routine clinical practice.
Cohort 6: Dapagliflozin with CVD; A comparator cohort which includes new users of dapagliflozin with established CVD for clinical characterization and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Dapagliflozin; No intervention or treatment assignment imposed by this study. Participants received dapagliflozin as a part of routine clinical practice.
Cohort 7: Empagliflozin or Dapagliflozin; A target cohort which includes new users of empagliflozin or dapagliflozin for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Empagliflozin; No intervention or treatment assignment imposed by this study. Participants received empagliflozin as a part of routine clinical practice.; Drug: Dapagliflozin; No intervention or treatment assignment imposed by this study. Participants received dapagliflozin as a part of routine clinical practice.
Cohort 8: Empagliflozin or Dapagliflozin with CVD; A target cohort which includes new users of empagliflozin or dapagliflozin with established CVD for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Empagliflozin; No intervention or treatment assignment imposed by this study. Participants received empagliflozin as a part of routine clinical practice.; Drug: Dapagliflozin; No intervention or treatment assignment imposed by this study. Participants received dapagliflozin as a part of routine clinical practice.
Cohort 9: DPP-4 inhibitor (i)/ GLP-1 agonist (a)/ other AHA; A comparator cohort which includes new users of any dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) agonist, or other select antihyperglycemic agents (AHA) for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors; No intervention or treatment assignment imposed by this study. Participants received DPP-4 inhibitor as a part of routine clinical practice. DPP-4 inhibitors includes: alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin.; Drug: Glucagon-like Peptide-1 (GLP-1) Agonist; No intervention or treatment assignment imposed by this study. Participants received GLP-1 agonist as a part of routine clinical practice. GLP-1 agonists includes: albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide.; Drug: Anti-hyperglycemic Agents (AHA); No intervention or treatment assignment imposed by this study. Participants received other selected AHA as a part of routine clinical practice. Other select AHAs includes: acarbose, bromocriptine, miglitol, nateglinide, repaglinide.
Cohort 10: DPP-4 (i)/ GLP-1 (a)/ other AHA with CVD; A comparator cohort which includes new users of any DPP-4 inhibitor, GLP-1 agonist, or other select AHA with established CVD for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors; No intervention or treatment assignment imposed by this study. Participants received DPP-4 inhibitor as a part of routine clinical practice. DPP-4 inhibitors includes: alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin.; Drug: Glucagon-like Peptide-1 (GLP-1) Agonist; No intervention or treatment assignment imposed by this study. Participants received GLP-1 agonist as a part of routine clinical practice. GLP-1 agonists includes: albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide.; Drug: Anti-hyperglycemic Agents (AHA); No intervention or treatment assignment imposed by this study. Participants received other selected AHA as a part of routine clinical practice. Other select AHAs includes: acarbose, bromocriptine, miglitol, nateglinide, repaglinide.
Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA; A comparator cohort which includes new users of any DPP-4 inhibitor, GLP-1 agonist, thiazolidinediones (TZD), sulfonylureas (SU), insulin, or other select AHA for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors; No intervention or treatment assignment imposed by this study. Participants received DPP-4 inhibitor as a part of routine clinical practice. DPP-4 inhibitors includes: alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin.; Drug: Glucagon-like Peptide-1 (GLP-1) Agonist; No intervention or treatment assignment imposed by this study. Participants received GLP-1 agonist as a part of routine clinical practice. GLP-1 agonists includes: albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide.; Drug: Anti-hyperglycemic Agents (AHA); No intervention or treatment assignment imposed by this study. Participants received other selected AHA as a part of routine clinical practice. Other select AHAs includes: acarbose, bromocriptine, miglitol, nateglinide, repaglinide.; Drug: Thiazolidinediones (TZD); No intervention or treatment assignment imposed by this study. Participants received TZD as a part of routine clinical practice. TZDs includes: pioglitazone, rosiglitazone, troglitazone.; Drug: Sulfonylureas (SU); No intervention or treatment assignment imposed by this study. Participants received SU as a part of routine clinical practice. SUs includes: glipizide, glyburide, glimepiride, chlorpropamide, tolazamide, tolbutamide, acetohexamide; Drug: Insulin; No intervention or treatment assignment imposed by this study. Participants received Insulin as a part of routine clinical practice.
Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD; A comparator cohort which includes new users of any DPP-4 inhibitor, GLP-1 agonist, TZD, SU, insulin, or other select AHA with established CVD for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors; No intervention or treatment assignment imposed by this study. Participants received DPP-4 inhibitor as a part of routine clinical practice. DPP-4 inhibitors includes: alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin.; Drug: Glucagon-like Peptide-1 (GLP-1) Agonist; No intervention or treatment assignment imposed by this study. Participants received GLP-1 agonist as a part of routine clinical practice. GLP-1 agonists includes: albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide.; Drug: Anti-hyperglycemic Agents (AHA); No intervention or treatment assignment imposed by this study. Participants received other selected AHA as a part of routine clinical practice. Other select AHAs includes: acarbose, bromocriptine, miglitol, nateglinide, repaglinide.; Drug: Thiazolidinediones (TZD); No intervention or treatment assignment imposed by this study. Participants received TZD as a part of routine clinical practice. TZDs includes: pioglitazone, rosiglitazone, troglitazone.; Drug: Sulfonylureas (SU); No intervention or treatment assignment imposed by this study. Participants received SU as a part of routine clinical practice. SUs includes: glipizide, glyburide, glimepiride, chlorpropamide, tolazamide, tolbutamide, acetohexamide; Drug: Insulin; No intervention or treatment assignment imposed by this study. Participants received Insulin as a part of routine clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Hospitalizations for Heart Failure	Number of hospital admissions with a primary diagnosis of 'heart failure' will be reported.	Approximately 4-years
Number of Participants with Below Knee Lower Extremity Amputation Events	Number of participants with new below-knee lower extremity amputation procedures, excluding recent (within 30 day) revisions will be reported.	Approximately 4-years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 22, 2018
• Primary Completion (ACTUAL): April 6, 2018
• Study Completion (ACTUAL): June 25, 2018

Study Registration Dates

• First Submitted: April 3, 2018
• First Submitted That Met QC Criteria: April 3, 2018
• First Posted (ACTUAL): April 10, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 27, 2018
• Last Update Submitted That Met QC Criteria: August 24, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Heart Failure; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin; Hypoglycemic Agents; Glucagon; Empagliflozin; Dipeptidyl-Peptidase IV Inhibitors; Canagliflozin; Glucagon-Like Peptide 1; 2,4-thiazolidinedione
• Other Study ID Numbers: CR108464; RRA-20250 (OTHER: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No