SGLT2 Inhibitors Linked to Higher Erythrocytosis Risk Without Increasing Blood Clot Events in Type 2 Diabetes: JAMA

The study, led by Dr. Maor Lewis from the Department of Family Medicine at Meuhedet Health Maintenance Organization in Tel-Aviv, Israel, analyzed data from over 269,000 adult patients with type 2 diabetes using records from Israel’s largest healthcare system. The research aimed to assess how frequently SGLT2is causes erythrocytosis—a condition characterized by elevated red blood cell levels—and whether this condition is associated with an increased risk of arterial or venous thrombosis.

Using a propensity score-matched design, the researchers compared new users of SGLT2is to those initiating either dipeptidyl peptidase 4 inhibitors (DPP-4is) or glucagon-like peptide 1 receptor agonists (GLP-1RAs). After matching, the final analysis included 68,776 patients in both the SGLT2i and DPP-4i groups and 65,756 in each of the SGLT2i and GLP-1RA groups.

Based on the study, the researchers reported the following findings:

• Patients who began SGLT2i therapy showed a 5.5% higher prevalence of erythrocytosis compared to DPP-4i users.
• Compared to GLP-1RA users, the prevalence of erythrocytosis was 5.8% higher among SGLT2i initiators.
• SGLT2i use was associated with a mean increase in hemoglobin levels by 0.37 g/dL.
• Hematocrit levels increased by 1.5% among patients taking SGLT2is.
• Male sex, smoking, and the use of empagliflozin (as opposed to dapagliflozin) were linked to a higher risk of developing erythrocytosis.
• Despite the rise in erythrocytosis, there was no significant increase in the risk of major cardiovascular or thrombotic events.
• The hazard ratio for myocardial infarction in patients with erythrocytosis was 0.92, indicating no elevated risk.
• The hazard ratio for venous thromboembolism was 1.56, which was also not statistically significant.
• The risk of stroke in patients with erythrocytosis remained statistically unchanged.

The authors noted that these findings provide significant reassurance about the clinical use of SGLT2 inhibitors. While these medications may cause a measurable increase in red blood cell counts, this effect does not appear to elevate the risk of clot-related complications. They further emphasized that the results add to the expanding body of evidence supporting the favorable cardiovascular safety profile of SGLT2 inhibitors.

According to the authors, ongoing monitoring of hematologic parameters in patients receiving SGLT2is may be advisable, particularly in those with other risk factors for erythrocytosis. However, the absence of a thrombotic signal should ease concerns among prescribers and patients alike.

Reference:

Lewis M, Burrack N, Heymann A, Grossman A, Neuman T, Abuhasira R. Sodium-Glucose Cotransporter 2 Inhibitors, Erythrocytosis, and Thrombosis in Adults With Type 2 Diabetes. JAMA Netw Open. 2025;8(6):e2517086. doi:10.1001/jamanetworkopen.2025.17086