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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Diabetes Mellitus, Type 2, Cardiovascular Diseases

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1: Canagliflozin<br>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<br>* No intervention or treatment assignment imposed by this study. Participants received canagliflozin as a part of routine clinical practice.<br>|
| Cohort 2: Canagliflozin with Cardiovascular Disease (CVD)<br>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<br>* No intervention or treatment assignment imposed by this study. Participants received canagliflozin as a part of routine clinical practice.<br>|
| Cohort 3: Empagliflozin<br>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<br>* No intervention or treatment assignment imposed by this study. Participants received empagliflozin as a part of routine clinical practice.<br>|
| Cohort 4: Empagliflozin with CVD<br>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<br>* No intervention or treatment assignment imposed by this study. Participants received empagliflozin as a part of routine clinical practice.<br>|
| Cohort 5: Dapagliflozin<br>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<br>* No intervention or treatment assignment imposed by this study. Participants received dapagliflozin as a part of routine clinical practice.<br>|
| Cohort 6: Dapagliflozin with CVD<br>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<br>* No intervention or treatment assignment imposed by this study. Participants received dapagliflozin as a part of routine clinical practice.<br>|
| Cohort 7: Empagliflozin or Dapagliflozin<br>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<br>* No intervention or treatment assignment imposed by this study. Participants received empagliflozin as a part of routine clinical practice.<br>Drug: Dapagliflozin<br>* No intervention or treatment assignment imposed by this study. Participants received dapagliflozin as a part of routine clinical practice.<br>|
| Cohort 8: Empagliflozin or Dapagliflozin with CVD<br>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<br>* No intervention or treatment assignment imposed by this study. Participants received empagliflozin as a part of routine clinical practice.<br>Drug: Dapagliflozin<br>* No intervention or treatment assignment imposed by this study. Participants received dapagliflozin as a part of routine clinical practice.<br>|
| Cohort 9: DPP-4 inhibitor (i)/ GLP-1 agonist (a)/ other AHA<br>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<br>* 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.<br>Drug: Glucagon-like Peptide-1 (GLP-1) Agonist<br>* 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.<br>Drug: Anti-hyperglycemic Agents (AHA)<br>* 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.<br>|
| Cohort 10: DPP-4 (i)/ GLP-1 (a)/ other AHA with CVD<br>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<br>* 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.<br>Drug: Glucagon-like Peptide-1 (GLP-1) Agonist<br>* 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.<br>Drug: Anti-hyperglycemic Agents (AHA)<br>* 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.<br>|
| Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA<br>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<br>* 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.<br>Drug: Glucagon-like Peptide-1 (GLP-1) Agonist<br>* 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.<br>Drug: Anti-hyperglycemic Agents (AHA)<br>* 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.<br>Drug: Thiazolidinediones (TZD)<br>* No intervention or treatment assignment imposed by this study. Participants received TZD as a part of routine clinical practice. TZDs includes: pioglitazone, rosiglitazone, troglitazone.<br>Drug: Sulfonylureas (SU)<br>* 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<br>Drug: Insulin<br>* No intervention or treatment assignment imposed by this study. Participants received Insulin as a part of routine clinical practice.<br>|
| Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD<br>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<br>* 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.<br>Drug: Glucagon-like Peptide-1 (GLP-1) Agonist<br>* 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.<br>Drug: Anti-hyperglycemic Agents (AHA)<br>* 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.<br>Drug: Thiazolidinediones (TZD)<br>* No intervention or treatment assignment imposed by this study. Participants received TZD as a part of routine clinical practice. TZDs includes: pioglitazone, rosiglitazone, troglitazone.<br>Drug: Sulfonylureas (SU)<br>* 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<br>Drug: Insulin<br>* No intervention or treatment assignment imposed by this study. Participants received Insulin as a part of routine clinical practice.<br>|

What is the study measuring?
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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 |