Secondary Erythrocytosis Among Type 2 Diabetes Mellitus Patients With Hypogonadism Using Sodium‐Glucose Cotransporter 2 Inhibitors and Testosterone Replacement Therapy

ABSTRACT Hypogonadism is commonly linked to type 2 diabetes mellitus (T2DM), with testosterone replacement therapy (TRT) representing a key treatment option. Sodium glucose cotransporter‐2 inhibitors (SGLT‐2i) class is part of T2DM management. Both treatments can increase Hct, Hb and RBC levels with a potential risk for secondary erythrocytosis. This study compares Hct, RBC and Hb changes between T2DM patients treated with and without SGLT‐2i and TRT for hypogonadism. Methods Data from Clalit Healthcare Services (2015–2023) was analysed from male T2DM patients with hypogonadism. Mixed linear regression assessed SGLT‐2i effects on Hct, Hb and RBC levels, while generalised estimation equations were used to predict the proportion of patients with Hct > 54%. Results In total, 5235 male patients met the inclusion criteria, with 3146 in the SGLT‐2i (+) group, while 2089 comprised the SGLT‐2i (−) group. Mean age was 63.8 ± 11.0 years, mean Hct was 43.3% ± 4.4%, BMI was 30.8 ± 5.2 kg/m2 and eGFR was 84.9 ± 19.3 mL/min/1.73m2. The SGLT‐2i (+) group demonstrated a statistically significant increase in Hct, Hb, and RBC after TRT initiation (p < 0.001). While the overall increase in Hct > 54% was not statistically significant after TRT initiation with OR = 1.85 [95% CI 0.96–3.67], p = 0.06. However, in the SGLT2i (+) group, it was significantly higher than for those in the SGLT2i (−) group, OR = 4.85 [95% CI 3.06–7.69], p = 0.02. Conclusions SGLT‐2i and TRT co‐administration are associated with an increased chance of developing secondary erythrocytosis in T2DM. Awareness and potential treatment discontinuation may prevent unnecessary investigations. Frequent monitoring of these parameters is essential.

Abstract licence: CC BY

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