Clinical trial NCT06779929: Emulation of the Study of Tirzepatide Compared with Dulaglutide on Major Cardiovascular Events in Participants with Type 2 Diabetes (SURPASS-CVOT)
Official title: Emulation of the Study of Tirzepatide Compared with Dulaglutide on Major Cardiovascular Events in Participants with Type 2 Diabetes (SURPASS-CVOT)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Type 2 Diabetes
Keywords: Tirzepatide
Dulaglutide
Type 2 diabetes
Cardiovascular disease
Myocardial infarction
Stroke
Mortality
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2025-01-17
Enrollment: 50000
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients \> 40 years old with T2D and established atherosclerotic cardiovascular disease.

Brief summary: 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.

Detailed 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).

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

Primary outcomes:
measure: Composite CV outcome
timeFrame: From treatment initiation to end of follow up, up to 48 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
References:
citation: Nicholls SJ, Bhatt DL, Buse JB, Prato SD, Kahn SE, Lincoff AM, McGuire DK, Nauck MA, Nissen SE, Sattar N, Zinman B, Zoungas S, Basile J, Bartee A, Miller D, Nishiyama H, Pavo I, Weerakkody G, Wiese RJ, D'Alessio D; SURPASS-CVOT investigators. Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics. Am Heart J. 2024 Jan;267:1-11. doi: 10.1016/j.ahj.2023.09.007. Epub 2023 Sep 25.