Semaglutide, Tirzepatide and the Cardiologist: Weight-Directed Therapy as Cardiovascular Therapy
DOI:
https://doi.org/10.5281/zenodo.22365904Abstract
For most of their clinical life, GLP-1 receptor agonists and the dual GLP-1/GIP agonist tirzepatide have been discussed in
cardiology mainly as diabetes or obesity drugs with cardiovascular side effects worth monitoring. Two recent trials
change that framing: SELECT showed semaglutide reduces major adverse cardiovascular events in patients who do not have diabetes, and STEP-HFpEF showed the same drug improves symptoms and function in obesity-related heart failure with preserved ejection fraction. Tirzepatide's own cardiovascular outcomes trial has also now reported, though with a different and more modest evidentiary claim.
References
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes" (SELECT). N Engl J Med 389(2023):2221-2232.
Kosiborod MN, Abildstrom SZ, Borlaug BA, et al. "Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity" (STEP-HFpEF). N Engl J Med 389(2023):1069-1084.
Deanfield J, Verma S, Scirica BM, et al. "Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial". Lancet 404(2024):773-786.
[Authors not independently confirmed beyond the indexed press release]. "Tirzepatide meets primary endpoint of noninferiority to dulaglutide for cardiovascular outcomes" (SURPASS-CVOT). Eli Lilly and Company, topline results, 31 July 2025.
