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

SGLT-2i use in T2DM patients with hypogonadism was associated with statistically significant increases in Hct, Hb, and RBC after TRT initiation.

• The SGLT-2i (+) group demonstrated a statistically significant increase in Hct, Hb, and RBC after TRT initiation (p < 0.001).
• Mixed linear regression was used to assess SGLT-2i effects on Hct, Hb, and RBC levels.
• The study included 3146 patients in the SGLT-2i (+) group and 2089 in the SGLT-2i (-) group.
• Mean baseline Hct was 43.3% ± 4.4% across all patients.

Patients in the SGLT-2i (+) group had significantly higher odds of developing Hct > 54% (secondary erythrocytosis threshold) compared to patients in the SGLT-2i (-) group.

• The odds of Hct > 54% in the SGLT-2i (+) group were significantly higher than in the SGLT-2i (-) group, OR = 4.85 [95% CI 3.06-7.69], p = 0.02.
• Generalised estimation equations were used to predict the proportion of patients with Hct > 54%.
• The overall increase in Hct > 54% after TRT initiation across all patients was not statistically significant, OR = 1.85 [95% CI 0.96-3.67], p = 0.06.

The study population consisted of 5235 male T2DM patients with hypogonadism drawn from Clalit Healthcare Services data from 2015 to 2023.

• Mean age was 63.8 ± 11.0 years.
• Mean BMI was 30.8 ± 5.2 kg/m².
• Mean eGFR was 84.9 ± 19.3 mL/min/1.73m².
• 3146 patients were in the SGLT-2i (+) group and 2089 were in the SGLT-2i (-) group.

Both SGLT-2 inhibitors and testosterone replacement therapy independently have the potential to increase hematocrit, hemoglobin, and red blood cell levels.

• Hypogonadism is commonly linked to type 2 diabetes mellitus, with TRT representing a key treatment option.
• SGLT-2 inhibitors are part of standard T2DM management.
• Both treatments can increase Hct, Hb, and RBC levels with a potential risk for secondary erythrocytosis.
• The background rationale for this study was the overlapping erythrocytosis-promoting effects of both drug classes in a population likely to receive both.

The authors recommend frequent monitoring of hematological parameters and consideration of treatment discontinuation in T2DM patients co-administered SGLT-2i and TRT.

• Awareness and potential treatment discontinuation may prevent unnecessary investigations.
• Frequent monitoring of Hct, Hb, and RBC parameters is described as essential.
• The finding that OR for Hct > 54% was 4.85 in the combined treatment group supports heightened clinical vigilance.