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

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.

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).

Eligibility Criteria:
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