Sodium–glucose cotransporter 2 inhibitor-associated erythrocytosis in type 2 diabetes: a retrospective cohort study

Abstract

Aims

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) increase haematocrit and may cause erythrocytosis, creating uncertainty in type 2 diabetes management. Most available data derive from administrative registries or mixed, non-diabetic and/or non-European population. This study aimed to assess the onset, clinical characteristics and management outcomes of people with type 2 diabetes developing SGLT2i-associated erythrocytosis in a routine clinical setting.

Methods

This retrospective, single-centre cohort study included adults with type 2 diabetes who developed at least one episode of erythrocytosis (haematocrit ≥ 48% in women, ≥ 49% in men) during the first year after initiation of SGLT2i therapy. Haemoglobin and haematocrit were collected at baseline, at erythrocytosis onset, and at 6 and 12 months with the first erythrocytosis episode defined as the “index date”. No time effect or effect modification across predictive variables was observed. Management included no intervention in 84.1%, SGLT2i discontinuation in 5.3%, and phlebotomy in 4.5%. JAK2 V617F testing was performed in 19 cases, yielding negative results.

Results

Erythrocytosis was detected in 3.4% of subjects (n = 132 out of 3,848). The cohort was predominantly male (87.9%), with a median age of 68.4 years and diabetes duration of 10.5 years. Cardiovascular comorbidities were common. The median time from SGLT2i initiation to erythrocytosis was 11.9 months. Over 12 months, haematocrit and haemoglobin levels remained stable, with no thrombotic events.

Conclusions

SGLT2i-associated erythrocytosis is an uncommon, stable, and seemingly low-risk phenomenon. However, it may trigger unnecessary interventions, including treatment discontinuation. These findings highlight a gap between the benign nature of this effect and real-world practice, supporting the need for evidence-based, multidisciplinary guidelines to preserve SGLT2i cardiorenal benefits and optimise patient management.