Endocrine Abstracts

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a promising class of medications, demonstrating a significant reduction in the risk of cardiovascular events. An associated consequence of SGLT2i is an increase in hematocrit levels, with cardiovascular outcome trials revealing frequent hematocrit mean elevations varying from +2.3% to 3.5%. This rise in hematocrit introduces a potential dilemma when evaluating the risk-benefit profile of SGLT2i in patients with high cardiovascular risk. While effectively reducing the relative risk of major cardiovascular events, the associated secondary polycythemia raises concerns about an elevated risk of thrombotic events. Notably, existing guidelines and recommendations do not address this specific concern, emphasizing the need for further exploration and guidance in managing hematological alterations associated with SGLT2i therapy.

Case series: To address this issue, we present a case series involving five male patients, with a median age of 53 years [41-61], diagnosed with type 2 diabetes for 6 years [1-12], all prescribed a daily dose of the SGLT2 inhibitor dapagliflozin. Only one patient was a former smoker. Baseline blood tests revealed normal hemogram values, including hemoglobin at 16.2 g/l [15.5-16.9], hematocrit at 47.2% [44.7-49.8], and erythrocytes at 5.33×10¹²/l [5.28-5.33]. Following a mean treatment duration of 3±1 months, a substantial increase was observed in both hemoglobin (17.8 g/dl [17.3-18.3], P=0.043) and hematocrit (51.2% [49.5-53.4], P=0.043), reaching peak values of 18.4 g/dl and 54.2%, respectively. However, there was no significant change in erythrocyte count (P=0.109). All patients underwent normal blood smear assessments, and their erythropoietin levels, electrolytes, kidney, and liver functions remained within the normal range. The absence of the JAK2 v617f mutation in all five patients ruled out Polycythemia Vera and other myeloproliferative disorders. In two cases, dapagliflozin was suspended, resulting in decreased hemoglobin levels (15.9 and 16.4 g/l) and reduced hematocrit (44% and 46.5%) after three and four months, without the need for phlebotomy. Conversely, for the remaining three patients, the cardiovascular benefits of dapagliflozin were deemed superior, and consequently, treatment continued in conjunction with periodic phlebotomies. In conclusion, these case reports demonstrate that SGLT2i-induced erythrocytosis accompanies the cardiovascular benefits of these drugs. Clinicians should maintain close monitoring of patients’ hemogram and carefully weigh the risk-benefit profile in an individualized approach, considering potential interventions such as drug suspension or therapeutic phlebotomy.