SURPASS-CVOT - cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes

SURPASS-CVOT investigated the cardiovascular outcomes of tirzepatide, a dual incretin agonist of the glucagon-like peptide-1 and glucose dependent insulinotropic polypeptide receptors, in patients with type 2 diabetes (1):

Methodology:

• conducted an active-comparator–controlled, double-blind, noninferiority trial in which patients with type 2 diabetes and atherosclerotic cardiovascular disease were randomly assigned in a 1:1 ratio to receive a weekly subcutaneous injection of tirzepatide (up to 15 mg) or dulaglutide (1.5 mg)
• primary end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke and was tested for noninferiority of tirzepatide to dulaglutide with a margin of 1.05 for the upper limit of the 95.3% confidence interval for the hazard ratio. An upper limit of less than 1.00 was considered to indicate superiority of tirzepatide to dulaglutide

Inclusion criteria:

• patients at least 40 years of age were eligible if they had type 2 diabetes with a glycated hemoglobin level between 7.0% (53 mmol per mole) and 10.5% (91 mmol per mole), a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 25,
• and established atherosclerotic cardiovascular disease in at least one vascular territory

Exclusion criteria:

• among the exclusion criteria were any cardiovascular event in the 60 days before screening, use of a GLP-1 receptor agonist or pramlintide in the 3 months before screening, planned treatment for diabetic retinopathy or macular edema, chronic advanced heart failure, a history of pancreatitis, a clinically significant abnormality in gastric emptying or previous bariatric surgery, active liver disease (not including metabolic dysfunction–associated steatohepatitis), an estimated glomerular filtration rate (eGFR) of less than 15 ml per minute per 1.73 m2 of body-surface area or use of longterm dialysis, or a family or personal history of
  multiple endocrine neoplasia or medullary thyroid carcinoma

Study results:

• a total of 13,299 patients underwent randomization; 134 were subsequently excluded because they did not meet inclusion criteria
  • patients were followed for a median of 4.0 years
  • the modified intention-to treat population thus included 6586 patients in the tirzepatide group and 6579 in the dulaglutide group
  • mean (±SD) age of the patients was 64.1±8.8 years, 29.0% were women, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 32.6±5.5, the mean glycated hemoglobin level was 8.4±0.9%, and the mean duration of diabetes was 14.7±8.8 years
  • a primary end-point event occurred in 801 patients (12.2%) in the tirzepatide group and 862 (13.1%) in the dulaglutide group (hazard ratio, 0.92; 95.3% confidence interval, 0.83 to 1.01; P = 0.003 for noninferiority; P = 0.09 for superiority)
  • incidence of adverse events appeared to be similar in the two groups, although more gastrointestinal adverse events were observed in the tirzepatide group

Study conclusions:

• among patients with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was noninferior to dulaglutide with respect to a composite of death from cardiovascular causes, myocardial infarction, or stroke

Reference:

1. Nicholls SJ et al; SURPASS-CVOT Investigators. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes. N Engl J Med. 2025 Dec 18;393(24):2409-2420.