Is it safe to use GLP-1 (Glucagon-like peptide-1) analogs, such as liraglutide (Victoza), semaglutide (Ozempic), or dulaglutide (Trulicity), in patients with a history of pulmonary embolism?

GLP-1 Receptor Agonists and Pulmonary Embolism Risk

GLP-1 receptor agonists can be used in patients with a history of pulmonary embolism, as current guidelines do not list prior venous thromboembolism as a contraindication or caution, though emerging evidence suggests a potential increased risk of deep vein thrombosis (but not pulmonary embolism) that warrants clinical vigilance. 1

Guideline-Based Contraindications and Cautions

The American College of Cardiology's expert consensus clearly outlines the contraindications and cautions for GLP-1 receptor agonists, and pulmonary embolism or venous thromboembolism history is notably absent from both lists. 1

Established contraindications include: 1

• History of serious hypersensitivity reaction to the drug
• Severe renal impairment or ESRD (for exenatide and lixisenatide specifically)
• Personal or family history of medullary thyroid cancer
• Multiple endocrine neoplasia syndrome type 2 (MEN2)

Established cautions include: 1

• History of pancreatitis (particularly for liraglutide)
• Severe renal impairment or ESRD (for liraglutide and semaglutide)
• Hypoglycemia risk when combined with insulin or sulfonylureas
• Gastroparesis or prior gastric surgery
• Diabetic retinopathy complications (particularly for semaglutide due to rapid glucose reduction)

Emerging Evidence on Venous Thromboembolism

Recent research presents conflicting data that requires careful interpretation:

Evidence suggesting potential harm:

• A 2025 meta-analysis of 39 randomized controlled trials (70,499 participants) found GLP-1 receptor agonists were associated with a significantly increased risk of deep vein thrombosis (OR 1.64,95% CI 1.14-2.36), with 25 additional DVT events per 10,000 person-years. 2
• This risk was particularly prominent in trials with treatment duration >1.5 years (OR 2.32) and in cardiovascular outcome trials (OR 2.18). 2
• A 2021 meta-analysis of the SUSTAIN and PIONEER trials specifically found semaglutide increased deep vein thrombosis risk by 266% (RR 3.66,95% CI 1.09-12.25). 3
• Critically, neither study found an increased risk of pulmonary embolism specifically. 2, 3

Evidence suggesting potential benefit:

• A 2025 target trial emulation study (540,258 patients) found GLP-1 receptor agonists were associated with a lower risk of VTE compared to DPP-4 inhibitors (HR 0.78,95% CI 0.73-0.83), including lower rates of both pulmonary embolism (HR 0.74) and deep vein thrombosis (HR 0.81). 4

Clinical Decision-Making Algorithm

For patients with a history of pulmonary embolism considering GLP-1 receptor agonist therapy:

1. Assess cardiovascular benefit potential: If the patient has type 2 diabetes with established atherosclerotic cardiovascular disease, GLP-1 receptor agonists (liraglutide, semaglutide, dulaglutide) provide proven cardiovascular mortality and MACE reduction benefits. 1, 5, 6

2. Evaluate current anticoagulation status: If the patient is on therapeutic anticoagulation for their prior PE, the theoretical DVT risk is substantially mitigated, making GLP-1 receptor agonist use more favorable. 2, 3

3. Consider alternative agents first: If the patient has no established cardiovascular disease and the primary indication is glycemic control, consider alternative agents (metformin, SGLT2 inhibitors) that lack any thrombotic signal. 1, 5

4. If proceeding with GLP-1 receptor agonist therapy:

   • Educate the patient about DVT warning signs (unilateral leg swelling, pain, warmth)
   • Consider more frequent monitoring in the first 1.5 years of therapy when DVT risk appears highest 2
   • Prioritize liraglutide or dulaglutide over semaglutide, given semaglutide's stronger DVT signal in meta-analysis 3

Important Caveats

The cardiovascular mortality benefit of GLP-1 receptor agonists in high-risk patients likely outweighs the potential DVT risk. Liraglutide reduced all-cause mortality by 15% (HR 0.85,95% CI 0.74-0.97) and cardiovascular death by 22% (HR 0.78,95% CI 0.66-0.93) in the LEADER trial. 1, 6 This mortality benefit in patients with established cardiovascular disease is substantial and should be the primary consideration when weighing risks and benefits.

The conflicting evidence on VTE risk may reflect differences in study design (randomized trials vs. real-world observational data) and comparator groups (placebo vs. active comparators like DPP-4 inhibitors). 4, 2 The absence of increased pulmonary embolism risk specifically in the meta-analyses is reassuring for patients with prior PE. 2, 3