Prevalence and thrombotic risk of SGLT-2 inhibitor-associated erythrocytosis: a retrospective cohort study

Abstract

Background: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors, widely used for type 2 diabetes and cardiorenal conditions, may induce erythrocytosis, potentially increasing cardiovascular risk. This study investigates its prevalence, risk factors, and thrombotic implications. Methods: In a single-center retrospective study, we analyzed 6787 patients prescribed SGLT-2 inhibitors (2014–2024). Erythrocytosis was defined as hemoglobin > 16.5 g/dL or hematocrit > 49% in men, > 16.0 g/dL or > 48% in women. We assessed prevalence, risk factors, and thrombotic events using logistic regression. Results: Erythrocytosis occurred in 1145 patients (16.9%) over a median follow-up of 530 days (IQR, 277–981), with a median hemoglobin rise of 1.0 g/dL (IQR, 0.4–1.8). Male sex (OR 3.24, 95% CI 2.47–4.26), BMI ≥ 25 kg/m2 (OR 1.97, 95% CI 1.63–2.39), and current smoking (OR 2.41, 95% CI 1.96–2.96) significantly increased risk (all p < 0.001), while age ≥ 70 years, hypertension, dyslipidemia, and chronic kidney disease were associated with reduced risk. Thrombosis was rare (0.5%, 33 patients) and associated with antiplatelet use (OR 3.57, 95% CI 1.60–7.97), anticoagulant use (OR 5.93, 95% CI 2.60–13.57), and baseline erythrocytosis (OR 3.75, 95% CI 1.41–9.96). Among 33 patients with thrombosis, five exhibited erythrocytosis at the time of the event and within the prior six months; all had arterial thrombosis associated with underlying conditions (atrial fibrillation, coronary calcification, atherosclerosis), not directly attributable to SGLT-2-induced erythrocytosis. Conclusions: SGLT-2 inhibitors are associated with a 16.9% prevalence of erythrocytosis, but thrombotic risk appears primarily driven by pre-existing conditions.