Obesity, Overweight, Type 2 Diabetes Mellitus
Conditions
Brief summary
Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
Detailed description
This is a non-randomized, non-interventional study that is part of the Randomized Controlled Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology (RCT-DUPLICATE) initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to assess the comparative effectiveness of semaglutide vs dulaglutide on cardiovascular outcomes in individuals typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes (T2DM) and overweight. Although many features of the target trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the target trial. Randomization cannot be achieved in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. The database study will be a new-user active-comparative study, conducted using 3 national United States claims databases, where the effect of semaglutide vs dulaglutide on the composite end point of all-cause mortality, myocardial infarction, or stroke will be assessed. Clinical guidelines during the study period recommended both injectable semaglutide and dulaglutide for the same indications of glucose lowering and cardiovascular risk reduction.
Interventions
DRUGSemaglutide
Initiation of injectable semaglutide described in electronic health records is used as the exposure.
DRUGDulaglutide
Initiation of dulaglutide described in electronic health records is used as the reference.
Sponsors
Brigham and Women's Hospital
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Study Period: Optum: Eligible cohort entry period between December 5, 2017 to November 30, 2025. MarketScan: Eligible cohort entry period between December 5, 2017 to September 30, 2023. Medicare: Eligible cohort entry period between December 5, 2017 to September 30, 2020. Inclusion Criteria: * Men or women aged 18 years or older * History of myocardial infarction, stroke, any surgical or percutaneous revascularization procedure * Use of antihypertensive or lipid-lowering drugs * Coronary, carotid, or peripheral artery disease * BMI greater than or equal to 25.0 mg/m2 * Type 2 diabetes
Exclusion criteria
* Medullary thyroid carcinoma * MEN syndrome type 2 * Malignancy * Type 1 diabetes * Secondary diabetes * End-stage renal disease or dialysis * Uncontrolled diabetic retinopathy or maculopathy * Pregnancy * History of bariatric surgery * Prior use of pramlintide or any GLP-1-RA, except semaglutide or dulaglutide * Cardiovascular event or intervention in the last 7 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of all-cause mortality, myocardial infarction, or stroke. | 1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA | To evaluate the comparative effect of injectable semaglutide vs dulaglutide on the composite of all-cause mortality, myocardial infarction, or stroke in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke | 1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA | To evaluate the comparative effect of injectable semaglutide vs dulaglutide on the individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight. |
| Composite of myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure | 1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA | To evaluate the comparative effect of injectable semaglutide vs dulaglutide on the composite of myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight. |
| Hospitalization for heart failure | 1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA | To evaluate the comparative effect of injectable semaglutide vs dulaglutide on the occurrence of heart failure hospitalizations in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight. |
| Hospitalization for unstable angina | 1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA | To evaluate the comparative effect of injectable semaglutide vs dulaglutide on hospitalizations for unstable angina in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight. |
| Coronary revascularization | 1 day after cohort entry until outcome, disenrollment, end of study period, death, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA | To evaluate the comparative effect of injectable semaglutide vs dulaglutide on the occurrence of coronary revascularization in patients typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with type 2 diabetes and overweight. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORShirley Wang, PhD, ScM
Brigham and Women's Hospital
PRINCIPAL_INVESTIGATORNils Krüger, MD
Brigham and Women's Hospital
Outcome results
None listed