Endocrine Abstracts

Background

Sodium glucose cotransporter-2 (SGLT-2) inhibitors have proven valuable in the management of type 2 diabetes. These agents are particularly effective in reducing hospitalisations with heart failure and cardiovascular mortality. Adverse effects are primarily centred on urogenital infections and hypovolaemia. Here, we report the case of a patient who developed asymptomatic erythrocytosis while taking empagliflozin.

Case report

A 44-year-old male patient with type 2 diabetes for 12 years, presented to diabetes clinic for review of suboptimal glycaemic control. He was treated with sitagliptin/metformin (50/1000 mg) BD and empagliflozin 10 mg once daily. Nine months later, his blood work showed erythrocytosis with haemoglobin (Hb) 18.3 g/dl (13.5–17.5), red blood cells (RBC) 6.34 × 10¹²/l (4.5–5.5), haematocrit (Hct) 0.53 (0.4–0.5), reticulocyte count 202 × 10⁹/l (50–100), normal white cell count 7.2 × 10⁹/l and normal platelet count 169 × 10⁹/l. The patient was asymptomatic and had no history of smoking, sleep apnoea, malignancy, testosterone use or exposure to high altitudes. Oxygen saturation was 98% on room air and BMI was 26 kg/m². Subsequent investigations showed packed red cells and reactive lymphocytes on blood film, normal erythropoietin level, normal SPEP, normal Hb electrophoresis and negative JAK2 V617F mutation. In the meantime, the patient decided to stop all anti-hyperglycaemic medications and relied solely on lifestyle modification for diabetes control. Coincidentally, erythrocytosis resolved spontaneously (Hb 17.4 g/dl, Hct 0.49) six months after stopping anti-hyperglycaemic agents. Follow-up in diabetes clinic revealed worsening glycaemic control (HbA1c 75 mmol/mol). At this point, he was restarted on empagliflozin 10 mg once daily. 4 months later, investigations showed recurrence of erythrocytosis (Hb 18.9 g/dl, Hct 0.55, RBC 6.6 × 10¹²/l). Empagliflozin was discontinued and 6 weeks later his blood work showed slight improvement in erythrocytosis (Hb 18.6 g/dl, Hct 0.53). CT thorax/abdomen/pelvis showed no evidence of hepatic, renal or adrenal masses. He is due to have repeat blood work.

Discussion

There are five reported cases of erythrocytosis during treatment with SGLT-2 inhibitors in the literature; two cases had no risk factors for increased haematocrit, two were associated with co-administration with testosterone and one was unmasking of polycythemia vera. Our patient did not have any risk factor for increased haematocrit and erythrocytosis appears to be coincidental with SGLT-2 inhibitor use. A degree of plasma volume depletion due to osmotic diuresis leading to a relative erythrocytosis would make mechanistic sense. As erythrocytosis may predispose to prothrombotic events such as myocardial infarction and stroke, our case highlights the importance of monitoring haematocrits in patients on SGLT-2 inhibitors.