Early erythrocytosis and predictors of hematocrit response after SGLT2 inhibitor initiation in type 2 diabetes

Sodium-glucose cotransporter-2 (SGLT2) inhibitors reproducibly increase hemoglobin and hematocrit, but prospective data on early threshold-defined erythrocytosis and patient-level predictors of hematocrit response remain limited. This prospective observational cohort study included 156 adults with type 2 diabetes who initiated dapagliflozin or empagliflozin and underwent complete blood count assessment at baseline and at 3 and 6 months. Hemoglobin increased from 14.3 (13.3–15.4) g/dL at baseline to 14.9 (13.9–16.0) g/dL at 3 months and 15.2 (14.1–16.1) g/dL at 6 months, while hematocrit increased from 44.1 (41.3–47.0)% to 45.9 (43.0–49.1)% and 46.2 (43.7–49.3)%, respectively (both p < 0.001). World Health Organization-defined erythrocytosis increased from 16.7% to 30.1% ( p < 0.001), and a pronounced hematocrit response, defined as an absolute increase of ≥ 3% to identify a more marked individual response, occurred in 34.0% of patients. Lower baseline hematocrit (OR 0.70 per 1% increase, p < 0.001), higher triglyceride level (OR 1.21 per 50 mg/dL increase, p = 0.047), and higher white blood cell count (OR 1.25 per 1 × 10³/µL increase, p = 0.027) independently predicted pronounced hematocrit response. In this prospective observational cohort, early hematologic changes were observed after SGLT2 inhibitor initiation; however, these findings represent associations and should not be interpreted as establishing causality.