emulation of the study of tirzepatide compared with dulaglutide on major cardiovascular events in participants with type 2 diabetes (surpass-cvot)

Conditions: Type 2 Diabetes

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.

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

Keywords: tirzepatide dulaglutide type 2 diabetes cardiovascular disease myocardial infarction stroke mortality