Does semaglutide (glucagon-like peptide-1 receptor agonist) cause erythrocytosis (increased red blood cell count)?

Semaglutide and Erythrocytosis: Current Evidence

There is no evidence that semaglutide (a GLP-1 receptor agonist) causes erythrocytosis. The available medical literature does not establish any association between semaglutide use and increased red blood cell counts.

Evidence Analysis

GLP-1 Receptor Agonists and Hematologic Parameters

The extensive clinical trials and guidelines reviewing semaglutide's safety profile do not mention erythrocytosis as an adverse effect. Multiple cardiovascular outcome trials (SUSTAIN-6, PIONEER 6, SELECT, SOUL) have thoroughly documented semaglutide's effects, focusing on:

• Cardiovascular outcomes 1, 2, 3
• Renal outcomes 4
• Weight management 1

None of these comprehensive studies report erythrocytosis as an adverse effect of semaglutide.

Medications Associated with Erythrocytosis

While semaglutide has not been linked to erythrocytosis, recent evidence shows that:

• SGLT2 inhibitors (a different class of diabetes medications) are associated with erythrocytosis 5, 6
• In a large cohort study, SGLT2 inhibitor use was associated with a 5.5-5.8% higher prevalence of erythrocytosis compared to DPP-4 inhibitors and GLP-1 receptor agonists 5
• The combination of SGLT2 inhibitors with testosterone replacement therapy significantly increases the risk of erythrocytosis compared to either treatment alone 6

Clinical Implications

Medication Selection for Patients at Risk of Erythrocytosis

For patients with concerns about erythrocytosis:

• Semaglutide appears to be a safe option without evidence of increasing red blood cell counts
• SGLT2 inhibitors should be used with caution, especially in:
  • Male patients (adjusted OR for erythrocytosis: 4.12) 5
  • Smokers (adjusted OR: 2.00) 5
  • Patients on testosterone replacement therapy 6

Monitoring Recommendations

For patients on GLP-1 receptor agonists like semaglutide:

• Routine monitoring of hematocrit is not specifically required based on current evidence
• Focus monitoring on known adverse effects including:
  • Gastrointestinal symptoms 1
  • Risk of aspiration during anesthesia 1
  • Gallbladder disorders 7

Safety Reassurance

Even with SGLT2 inhibitor-induced erythrocytosis:

• No increased risk of thrombotic events has been observed 5
• No increased risk of myocardial infarction (HR 0.92), venous thromboembolism (HR 1.56), or stroke (HR 1.26) was found 5

Conclusion

Based on the most recent and highest quality evidence, semaglutide does not cause erythrocytosis. If erythrocytosis is observed in a patient taking semaglutide, clinicians should investigate other causes or concomitant medications, particularly SGLT2 inhibitors or testosterone replacement therapy.