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

NCT03492580 | Completed

• 2 other identifiers: CR108464RRA-20250
• Study Type: observational
• Target: 714,582
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 2; Cardiovascular Diseases

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (12)

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

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

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

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

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

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

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; Drug: Dapagliflozin

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; Drug: Dapagliflozin

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; Drug: Glucagon-like Peptide-1 (GLP-1) Agonist; Drug: Anti-hyperglycemic Agents (AHA)

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; Drug: Glucagon-like Peptide-1 (GLP-1) Agonist; Drug: Anti-hyperglycemic Agents (AHA)

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; Drug: Glucagon-like Peptide-1 (GLP-1) Agonist; Drug: Anti-hyperglycemic Agents (AHA); Drug: Thiazolidinediones (TZD); Drug: Sulfonylureas (SU); Drug: Insulin

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; Drug: Glucagon-like Peptide-1 (GLP-1) Agonist; Drug: Anti-hyperglycemic Agents (AHA); Drug: Thiazolidinediones (TZD); Drug: Sulfonylureas (SU); Drug: Insulin

Interventions

Canagliflozin DRUG

No intervention or treatment assignment imposed by this study. Participants received canagliflozin as a part of routine clinical practice.

Cohort 1: Canagliflozin; Cohort 2: Canagliflozin with Cardiovascular Disease (CVD)

Empagliflozin DRUG

No intervention or treatment assignment imposed by this study. Participants received empagliflozin as a part of routine clinical practice.

Cohort 3: Empagliflozin; Cohort 4: Empagliflozin with CVD; Cohort 7: Empagliflozin or Dapagliflozin; Cohort 8: Empagliflozin or Dapagliflozin with CVD

Dapagliflozin DRUG

No intervention or treatment assignment imposed by this study. Participants received dapagliflozin as a part of routine clinical practice.

Cohort 5: Dapagliflozin; Cohort 6: Dapagliflozin with CVD; Cohort 7: Empagliflozin or Dapagliflozin; Cohort 8: Empagliflozin or Dapagliflozin with CVD

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors DRUG

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.

Cohort 10: DPP-4 (i)/ GLP-1 (a)/ other AHA with CVD; Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA; Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD; Cohort 9: DPP-4 inhibitor (i)/ GLP-1 agonist (a)/ other AHA

Glucagon-like Peptide-1 (GLP-1) Agonist DRUG

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.

Cohort 10: DPP-4 (i)/ GLP-1 (a)/ other AHA with CVD; Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA; Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD; Cohort 9: DPP-4 inhibitor (i)/ GLP-1 agonist (a)/ other AHA

Anti-hyperglycemic Agents (AHA) DRUG

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; Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA; Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD; Cohort 9: DPP-4 inhibitor (i)/ GLP-1 agonist (a)/ other AHA

Thiazolidinediones (TZD) DRUG

No intervention or treatment assignment imposed by this study. Participants received TZD as a part of routine clinical practice. TZDs includes: pioglitazone, rosiglitazone, troglitazone.

Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA; Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD

Sulfonylureas (SU) DRUG

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

Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA; Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD

Insulin DRUG

No intervention or treatment assignment imposed by this study. Participants received Insulin as a part of routine clinical practice.

Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA; Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Janssen Investigative Site

Titusville, New Jersey, 08560, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Cardiovascular Diseases

Interventions

Canagliflozin; empagliflozin; dapagliflozin; Glucagon-Like Peptide 1; Thiazolidinediones; Sulfonylurea Compounds; Insulin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Thiazoles; Azoles; Urea; Amides; Sulfones; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2018
• First Posted: April 10, 2018
• Study Start: February 22, 2018
• Primary Completion: April 6, 2018
• Study Completion: June 25, 2018
• Last Updated: June 25, 2025

Record last verified: 2025-06

Locations

US (1)