Comment on 'Semaglutide and Tirzepatide Effects on Cardiovascular Outcomes in People With Overweight or Obesity in the Real World (STEER)'.
Journal
Diabetes, obesity & metabolism
ISSN
1463-1326
Date Issued
2026-02-26
Author(s)
Abstract
This retrospective analysis by Wilson et al. [1] comparing semaglutide and tirzepatide provides valuable real world information regarding incretin-based therapies in patients with obesity and established ASCVD. The study addresses a clinically pivotal question, and the effort to evaluate comparative cardiovascular outcomes in routine practice is judicious. However, the inference of lower major adverse cardiovascular events (MACE) with semaglutide may warrant additional methodological and analytic consideration, particularly regarding cohort interchangeability and interpretation of causality. Actually, the index period encompassed different regulatory and adoption phases for both medications. Semaglutide was widely implemented following established cardiovascular outcome data for near 10 years, whereas tirzepatide entered clinical practice later under advancing indications. Such temporal differences will inaugurate calendar time confounding, including changes with probable background cardioprotective medications, and healthcare utilisation styles that propensity matching may not fully catch up [2]. Even with extensive adjustment, residual confounding bias related to prescribing context should be considered. The early separation of MACE curves also merits more cautious interpretation. Atherosclerotic risk modification generally requires sustained exposure and plaque stabilisation, and rapid divergence in 8 months may reflect therapeutic channelling or immortal time bias rather than intrinsic biological differences between therapies [3]. This possibility is especially relevant when therapeutic adoption follows evidence maturity in different stages. Furthermore, individual MACE components would not be independently significant, and composite significance could depend on heterogeneous outcomes without determination. Such findings may complicate interpretation of comparative clinical benefit, since composite cardiovascular outcomes can be sensitive to variations in variable component event rates [4, 5]. Therefore, the study may be considered to be most appropriately interpreted as hypothesis-generating observational evidence rather than definitive comparative cardiovascular efficacy. These considerations along with established epidemiologic principles indicate that observational comparative effectiveness analyses cannot substitute for randomised cardiovascular outcome trials [2, 3, 6]. The author has nothing to report. The author has nothing to report. The author declares no conflicts of interest. Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/dom.70618.
Type
letter