Atherosclerotic Cardiovascular Disease, Type2 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 tirzepatide vs sitagliptin as a placebo proxy, after the pivotal RCT SURPASS-CVOT (NCT04255433) and its emulation (NCT07088718) demonstrated non-inferiority, leaving both regulators and clinical guideline committees uncertain whether to approve and recommend tirzepatide for a cardiovascular indication. This comparative effectiveness target trial described below draws from eligibility criteria from the SURPASS-CVOT trial and its emulation. 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 purpose of this protocol is to specify the target trial assessing the comparative effectiveness of the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1-RA) tirzepatide vs the dipeptidyl peptidase-4 inhibitors (DPP4i) sitagliptin on atherosclerotic cardiovascular end points in patients with type 2 diabetes and atherosclerotic cardiovascular disease. The database study will be a new-user active-comparative study, conducted using 2 national United States claims databases, where we compare the effect of tirzepatide vs sitagliptin in preventing atherosclerotic cardiovascular events. Clinical guidelines during the study period recommended both agents under investigation as second-line options for glucose lowering and were similarly costly.
Interventions
DRUGInitiation of tirzepatide
New use of tirzepatide dispensing claim is used as the exposure.
DRUGInitiation of sitagliptin
New use of sitagliptin dispensing claim is used as the reference.
Sponsors
Brigham and Women's Hospital
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* History of MI or stroke, surgical or percutaneous coronary/carotid peripheral artery revascularization, amputation, diagnosis of coronary/carotid/peripheral artery disease * BMI ≥25.0kg/m2 * Type 2 diabetes * Age ≥40 years * Male or female sex
Exclusion criteria
* Medullary thyroid carcinoma, MEN syndrome type 2, malignancy * Treatment for diabetic retinopathy/macular edema, heart failure NYHA IV, gastric emptying abnormality/bariatric surgery, end-stage renal disease or dialysis, pregnancy * Prior use of pramlintide or any GLP-1-RA except tirzepatide, * Pancreatitis, liver disease * Cardiovascular event or intervention, hospitalization for heart failure * Concurrent use of both drugs i.e. tirzepatide and sitagliptin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major adverse cardiovascular events | 1 day after cohort entry date until the first of outcome or censoring, up to 365 days | To evaluate the comparative effect of tirzepatide vs sitagliptin on the composite of myocardial infarction, stroke, or all-cause mortality in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite of myocardial infarction or stroke | 1 day after cohort entry date until the first of outcome or censoring, up to 365 days | To evaluate the comparative effect of tirzepatide vs sitagliptin on the composite of myocardial infarction or stroke in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial. |
| Myocardial infarction | 1 day after cohort entry date until the first of outcome or censoring, up to 365 days | To evaluate the comparative effect of tirzepatide vs sitagliptin at preventing myocardial infarction in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial. |
| Stroke | 1 day after cohort entry date until the first of outcome or censoring, up to 365 days | To evaluate the comparative effect of tirzepatide vs sitagliptin at preventing stroke in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial. |
| All-cause mortality | 1 day after cohort entry date until the first of outcome or censoring, up to 365 days | To evaluate the comparative effect of tirzepatide vs sitagliptin at preventing all-cause mortality in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial. |
| Infection-related mortality | 1 day after cohort entry date until the first of outcome or censoring, up to 365 days | To evaluate the comparative effect of tirzepatide vs sitagliptin at preventing infection-related mortality in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial. |
| Composite of myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. | 1 day after cohort entry date until the first of outcome or censoring, up to 365 days | To evaluate the comparative effect of tirzepatide vs sitagliptin on the composite of myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial. |
| Serious bacterial infections | 1 day after cohort entry date until the first of outcome or censoring, up to 365 days | To evaluate the comparative effect of tirzepatide vs sitagliptin on the safety outcome of serious bacterial infections in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial. |
| Urinary tract infections | 1 day after cohort entry date until the first of outcome or censoring, up to 365 days | To evaluate the comparative effect of tirzepatide vs sitagliptin on the safety outcome of urinary tract infections in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial. |
| Gastrointestinal adverse events | 1 day after cohort entry date until the first of outcome or censoring, up to 365 days | To evaluate the comparative effect of tirzepatide vs sitagliptin on the safety outcome of gastrointestinal adverse events in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial. |
| Infections across care settings | 1 day after cohort entry date until the first of outcome or censoring, up to 365 days | To evaluate the comparative effect of tirzepatide vs sitagliptin on the safety outcome of infections across care settings in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial. |
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