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May 19, 2026Frontiers in MedicineOpen Access

Tirzepatide initiation was associated with a significantly lower 1-year risk of venous thromboembolism compared with GLP-1 receptor agonists in patients with obesity (HR 0.90).

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Why the study?

Although GLP-1 RAs have been associated with potential reductions in VTE risk, evidence regarding the comparative effectiveness of tirzepatide on VTE risk in patients with obesity remains limited.

Does tirzepatide reduce the risk of venous thromboembolism in adults with obesity compared to GLP-1 receptor agonists?

Population

701,374 matched adults with obesity

Comparison

Tirzepatide vs GLP-1 RAs

Design

Retrospective, active-comparator, new-user propensity-matched cohort study

Follow-up

1-year

Key result

Tirzepatide initiation was associated with a significantly lower 1-year risk of venous thromboembolism compared with GLP-1 receptor agonists in patients with obesity (HR 0.90).

Authors

JWJheng-Yan WuKLKeng-Wei LeeSHSheng-Chi Huang

Discussion

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Member takes

Overview

Should not yet change prescribing; leaves open whether tirzepatide reduces VTE versus GLP-1 RAs in randomized trials.

Study Design

Type

Cohort (n=701,374)

Multicenter

Yes

Structured PICO

Does tirzepatide reduce the risk of venous thromboembolism in adults with obesity compared to GLP-1 receptor agonists?

P
Population
701,374 adults with obesity initiating either tirzepatide or GLP-1 receptor agonists, matched for baseline characteristics, followed for up to 1 year.
E
Exposure
Tirzepatide initiation (new users)
C
Comparator
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) initiation (new users)
O
Outcome
1-year incidence of venous thromboembolism (VTE)hard clinical

Main Result

Hazard Ratio: 0.9 (95% CI 0.83–0.98)

Absolute Event Rate: 0.3% vs 0.4%

p-value: p=0.011

In adults with obesity, tirzepatide initiation was associated with a significantly lower 1-year risk of venous thromboembolism compared with GLP-1 receptor agonists, driven by reductions in pulmonary embolism and all-cause mortality.

Limitations

  • Risk of misidentification and underrepresentation in registry-based database
  • Misclassification bias from use of diagnostic codes
  • Duration of therapy could not be reliably ascertained
  • Residual unmeasured confounding
  • GLP-1RAs analyzed as a class, introducing heterogeneity
  • Specific causes of mortality unavailable
  • Registry-based database with risk of misidentification and underrepresentation
  • Use of diagnostic codes raises possibility of misclassification bias
  • Differences in treatment-related weight loss and metabolic improvements could not be fully accounted for
  • Calendar time was not explicitly adjusted for in the propensity score model
  • Potential unmeasured confounding

Cite This Study

Wu et al. (2026) conducted a cohort in Obesity (n=701,374). Tirzepatide vs. GLP-1 receptor agonists was evaluated on 1-year incidence of venous thromboembolism (VTE) (HR 0.90, 95% CI 0.83-0.98, p=0.011). Tirzepatide initiation was associated with a significantly lower 1-year risk of venous thromboembolism compared with GLP-1 receptor agonists in patients with obesity (HR 0.90).

synapsesocial.com/papers/6a95d738d6dd5cd2182505bfhttps://doi.org/10.3389/fmed.2026.1820366
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Tirzepatide and reduced risk of pulmonary embolism and deep vein thrombosis: a multicenter U.S. cohort study2026
  2. 2Tirzepatide and risk of newly diagnosed aortic stenosis in patients with obesity: a multi-institutional real-world cohort study2026
  3. 3Cardiovascular Outcomes With Tirzepatide Versus <scp>GLP</scp> ‐1 Receptor Agonists in Overweight or Obesity: A Systematic Review and Meta‐Analysis2026 · 1 citations
  4. 4Real‐World Cardiovascular Outcomes of Obesity Treatment With Tirzepatide Versus Semaglutide in Non‐Diabetic Adults2026 · 1 citations
  5. 5An Observational Study of Cardiovascular Outcomes of Tirzepatide vs Glucagon-Like Peptide-1 Receptor Agonists2025 · 28 citations