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

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.