From the Guidelines
Semaglutide therapy is not associated with an increased risk of thrombosis based on current evidence. Clinical trials and post-marketing surveillance of semaglutide and other GLP-1 receptor agonists have not demonstrated a significant association with thromboembolic events, as seen in the SUSTAIN-6 trial 1 and PIONEER 6 trial 1. In fact, some research suggests these medications may have cardiovascular protective effects, as demonstrated in cardiovascular outcome trials where semaglutide reduced major adverse cardiovascular events in high-risk patients. The medication works by improving glycemic control, promoting weight loss, and potentially having beneficial effects on vascular function and inflammation, which could theoretically reduce rather than increase thrombosis risk.
Key Findings
- The SUSTAIN-6 trial showed that semaglutide reduced the primary outcome of cardiovascular death, nonfatal MI, or nonfatal stroke by 26% compared to placebo 1.
- The PIONEER 6 trial demonstrated that oral semaglutide was noninferior to placebo for the primary composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke 1.
- A meta-analysis of trials reported that GLP-1 receptor agonists, including semaglutide, reduce the risk of atherosclerotic major adverse cardiovascular events to a comparable degree in people with type 2 diabetes 1.
Clinical Implications
- Patients with diabetes already have an elevated baseline risk of thrombotic events due to the disease itself, but semaglutide does not appear to exacerbate this risk.
- Common side effects of semaglutide include gastrointestinal symptoms like nausea, vomiting, and diarrhea, but thrombosis is not considered a safety concern for this medication class.
- As with any medication, patients should report unusual symptoms like severe leg pain, chest pain, or shortness of breath to their healthcare provider promptly.
- The most recent guidelines from 2023 support the use of semaglutide for reducing the risk of major adverse cardiovascular events in patients with type 2 diabetes and established cardiovascular disease 1.
From the Research
Thrombosis Risk Associated with Semaglutide
- The risk of thrombosis associated with semaglutide therapy has been evaluated in several studies 2, 3, 4, 5, 6.
- A meta-analysis of the PIONEER and SUSTAIN trials found that semaglutide significantly increased the risk of deep vein thrombosis (RR 3.66,95% CI 1.09-12.25; I2 = 0) 2.
- Another study found that semaglutide reduced the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P<0.001 for noninferiority) 3.
- A review of the safety of semaglutide found that it induces mostly mild-to-moderate and transient gastrointestinal disturbances and increases the risk of biliary disease (cholelithiasis), but no unexpected safety issues have arisen to date 4.
- A study on the risks and benefits of semaglutide found that it is associated with concerning adverse effects like acute pancreatitis, anesthetic risks, acute kidney injury, acute gallbladder injury, nonarteritic anterior ischemic optic neuropathy, and diabetic retinopathy 5.
- A trial on oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes found that oral semaglutide was associated with a significantly lower risk of major adverse cardiovascular events than placebo, without an increase in the incidence of serious adverse events 6.
Key Findings
- Semaglutide increases the risk of deep vein thrombosis 2.
- Semaglutide reduces the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke 3.
- Semaglutide has a favorable risk/benefit profile for patients with type 2 diabetes 4.
- Semaglutide is associated with several adverse effects, including acute pancreatitis and diabetic retinopathy 5.
- Oral semaglutide reduces the risk of major adverse cardiovascular events in high-risk type 2 diabetes patients 6.