Cardiovascular Outcomes in Participants With Type 2 Diabetes Mellitus (T2DM)

Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus

The purpose of this study is to identify and evaluate the event rate of the composite endpoint of all-cause mortality (ACM) or hospitalization for heart failure (HF) for participants with Type 2 Diabetes mellitus (T2DM) and established cardiovascular (CV) disease among new users of sodium-glucose co-transporter 2 inhibitor (SGLT2i) as compared with new users of non-SGLT2i anti-hyperglycemic agent (AHA).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Dipeptidyl Peptidase-4 Inhibitor (DPP-4); Drug: Glucagon-Like Peptide-1 Agonist (GLP-1); Drug: Thiazolidinedione (TZD); Drug: Sulfonylureas; Drug: Insulin; Drug: Canagliflozin; Drug: Empagliflozin; Drug: Dapagliflozin

• Study Type: Observational
• Enrollment (Actual): 25358

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Trevose, Pennsylvania, United States, 19053
      • Health ResearchTx, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• 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 using the military health system (MHS) over a 3-year period (4/01/2013 to 3/31/2016) will be observed for the cardiovascular outcomes.

Description

Inclusion Criteria:

• Type 2 diabetes mellitus (T2DM), defined as: greater than or equal to (>=) 1 anti-hyperglycemic agent (AHA) medication in the study period, and; >=1 diagnosis of T2DM in any available diagnosis field on or prior to index
• Established cardiovascular disease, defined as >=1 diagnosis in any diagnosis field for any of the following conditions: cerebrovascular disease; coronary artery disease (including heart failure [HF]); peripheral artery disease
• >=1-year pre-index continuous eligibility; enrollment gaps of less than or equal to (<=) 30 days will be considered continuous enrollment

Exclusion Criteria:

• Type 1 Diabetes mellitus (T1DM) diagnosis on or prior to the index date
• Secondary diabetes mellitus (DM) on or prior to the index date
• Missing sex data

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1: Non-SGLT2i new Users; This is a retrospective cohort study identifying participants with type 2 diabetes mellitus (T2DM) and established cardiovascular (CV) disease using the Military Health System (MHS) over a 3-year period. Cohort 1 included participants with incident exposure of one or more non-sodium glucose co-transporter 2 inhibitor (SGLT2i) anti-hyperglycemic agent (AHA) therapy during the study period with no prior or subsequent SGLT2i exposure throughout the study period. New users are defined as participants whose first exposure to any non-metformin AHA medication occurs greater than or equal to (>=) 365 days after their start of observation in the database with no prior exposure to any medication within the same AHA medication class in the prior 365 days.	Drug: Dipeptidyl Peptidase-4 Inhibitor (DPP-4); Participants who received a DPP-4 as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.; Drug: Glucagon-Like Peptide-1 Agonist (GLP-1); Participants who received a GLP-1 as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.; Drug: Thiazolidinedione (TZD); Participants who received a TZD as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.; Drug: Sulfonylureas; Participants who received a sulfonylureas as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.; Drug: Insulin; Participants who received a insulin as a part of routine clinical practice and met new user criteria, will be included in non-SGLT2i new users group.
Cohort 2: SGLT2i new Users; Cohort 2 included participants with incident SGLT2i exposure during the study period regardless of prior or concurrent exposure to one or more additional AHA therapy. New users are defined as participants whose first exposure to SGLT2i medication occurs >= 365 days after their start of observation in the database with no prior exposure to the same AHA medication class in the prior 365 days.	Drug: Canagliflozin; Participants who received canagliflozin as a part of routine clinical practice and met new user criteria, will be included in SGLT2i new user group.; Drug: Empagliflozin; Participants who received empagliflozin as a part of routine clinical practice and met new user criteria, will be included in SGLT2i new user group.; Drug: Dapagliflozin; Participants who received dapagliflozin as a part of routine clinical practice and met new user criteria, will be included in SGLT2i new user group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate of the Composite of All-cause Mortality (ACM) or Hospitalization for Heart Failure (HF)	Composite of ACM and hospitalization of HF will be assessed in participants with type 2 diabetes mellitus. ACM is defined as any record of death regardless of the cause of death and is identified through a master death file within the military health system (MHS) that compiles, processes, and validates all death records from the following data sources: inpatient hospitalization discharge dispositions from military and civilian hospitals, ambulatory and outpatient encounter records with recorded death disposition, casualty death feed related to active duty service member combat related deaths, survivor self-report, and an established, recurring social security death index (SSDI) feed from the social security administration. Hospitalization for HF will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an international classification of disease-9th or 10th edition (ICD-9/10) in the primary diagnosis field.	approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate of All-Cause Mortality	ACM is defined as any record of death regardless of the cause of death and is identified through a master death file within MHS that compiles, processes, and validates all death records from the following data sources: inpatient hospitalization discharge dispositions from military and civilian hospitals, ambulatory and outpatient encounter records with recorded death disposition, casualty death feed related to active duty service member combat related deaths, survivor self-report, and an established, recurring SSDI feed from the social security administration.	approximately 3 years
Incidence Rate of Hospitalization for HF	Hospitalization for HF will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an international classification of disease-9th or 10th edition (ICD-9/10) in the primary diagnosis field.	approximately 3 years
Incidence Rate of Major Adverse Cardiovascular Events (MACE)	MACE will be defined as the composite endpoint of ACM, non-fatal stroke, or non-fatal myocardial infarction (MI).	approximately 3 years
Incidence Rate of Composite of MACE or Hospitalization for HF	Participants for composite of ACM and hospitalization of HF will be assessed. MACE will be defined as the composite endpoint of ACM, non-fatal stroke, or non-fatal myocardial infarction (MI). Hospitalization for HF will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an international classification of disease-9th or 10th edition (ICD-9/10) in the primary diagnosis field.	approximately 3 years
Incidence Rate of Non-fatal stroke	Non-fatal stroke will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an ICD-9/10 in the primary diagnosis field pertaining to either ischemic stroke or hemorrhagic stroke and the participant did not die during the index hospitalization.	approximately 3 years
Incidence Rate of Non-Fatal Myocardial Infarction	Non-fatal MI will be defined as any inpatient hospitalization record, inclusive of both military and civilian hospitals, with an ICD-9/10 in the primary diagnosis field and the participant did not die during the index hospitalization.	approximately 3 years
Percentage of Participants With Below Knee Lower Extremity (BKLE) Amputation	The occurrence of a below-knee lower extremity amputation will be defined by observing an associated procedure code in the outpatient or inpatient medical service claims.	approximately 3 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2016
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: August 11, 2017
• First Submitted That Met QC Criteria: August 11, 2017
• First Posted (Actual): August 15, 2017

Study Record Updates

• Last Update Posted (Actual): November 21, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; 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; Glucagon; Empagliflozin; Dipeptidyl-Peptidase IV Inhibitors; Canagliflozin; Glucagon-Like Peptide 1; 2,4-thiazolidinedione
• Other Study ID Numbers: CR108355; RRA-17640 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

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