Emulation of the Study of Tirzepatide Compared with Dulaglutide on Major Cardiovascular Events in Participants with Type 2 Diabetes (SURPASS-CVOT)

Mass General Brigham

Status

Active, not recruiting

Conditions

Type 2 Diabetes

Treatments

Drug: Tirzepatide

Drug: Dulaglutide

Study type

Observational

Funder types

Other

Identifiers

NCT06779929

2024P001317

Details and patient eligibility

About

This cohort study was initiated to emulate the design of the SURPASS-CVOT trial using observational analogues of the trial design components in a study based on insurance claims data.

Full description

Recent evidence suggests that the metabolic effects of glucagon-like peptide-1 receptor agonists (GLP-1RA) can be enhanced by combining them with the actions of other entero-pancreatic hormones, such as glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon. Tirzepatide is a once-weekly GIP/GLP-1RA, approved for the treatment of type 2 diabetes in May 2022.

The Study of Tirzepatide Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes (SURPASS-CVOT; NCT04255433) is an event-driven, randomized, double- blind, active comparator, parallel-group study, to evaluate cardiovascular (CV) outcomes with tirzepatide treatment in people with type 2 diabetes (T2D) and established atherosclerotic CV disease (ASCVD) compared with dulaglutide treatment, stratified by baseline sodium-glucose cotransporter-2 (SGLT2) inhibitors use. SURPASS-CVOT was designed to establish CV protection with tirzepatide by demonstrating noninferiority of tirzepatide to dulaglutide, and also to determine whether tirzepatide produces a greater CV benefit than dulaglutide (superiority analysis).

This new user active comparator cohort study aims to emulate the SURPASS-CVOT trial using insurance claims data. Trial design parameters were adapted in claims data using observational analogues for eligibility criteria, treatment strategies, treatment assignment, follow-up start, follow-up end, outcome, and causal contrast. We also conducted HbA1c-adjusted analyses among those with HbA1c values (54% of population).

Enrollment

50,000 estimated patients

Sex

All

Ages

40+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with T2D who were new users of tirzepatide or new users of dulaglutide
AND established ASCVD defined as:
- History of Myocardial Infarction (MI) or MI sequela
- Unstable or stable angina
- Coronary atherosclerosis disease or procedures
- Ischemic stroke
- Peripheral arterial disease or procedures
- Atherosclerotic cerebrovascular disease or cerebrovascular procedures
- Lower-limb amputation
Age >= 40 years old
Patients with at least 180 days of continuous health plan enrollment before and including the treatment initiation date

Exclusion criteria

Patients with Type 1 diabetes mellitus
Patients with missing age or sex information
Patients with history of proliferative diabetic retinopathy, panretinal photocoagulation, vitreous hemorrhage, or intravitreal anti-VEGF injection
Patient within history of left ventricular assisted device (LVAD) or heart transplant
Patients with any previous organ transplants
Patients with acute of chronic pancreatitis
Patients with gastroparesis, bowel obstruction or bariatric surgery
Patient with CKD Stage 5, end stage kidney disease, kidney transplant, or hemodialysis
Patients with multiple endocrine neoplasm syndrome type 2 (MEN-2)
Patient with cancer
Pregnant women
Patient with diabetic ketoacidosis or HONK within the last year to treatment initiation
Patients with acute hepatitis within the last year to treatment initiation
Patients with elevated serum calcitonin level within the last year to treatment initiation
Previous exposure to GLP-1RA or pramlintide during the 180-days washout period and including treatment initiation date
Patients with severe hypoglycemia within the last 6 months to treatment initiation
Patients with hospitalization for heart failure within the last 60 days to treatment initiation
Patient with acute coronary syndrome, ischemic stroke, peripheral arterial disease, or coronary or cerebrovascular procedure within the last 60 days to treatment initiation
Patients with prescription dispensing for both tirzepatide and dulaglutide on treatment initiation date