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

IF 2.7 Q3 ENDOCRINOLOGY & METABOLISM

Endocrinology, Diabetes and Metabolism Pub Date : 2025-06-03 DOI:10.1002/edm2.70064

Maharan Kabha, Hadar Dana, Sameer Kassem, Yoram Dekel, Hilla Cohen, Adnan Zaina

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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.

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钠-葡萄糖共转运蛋白2抑制剂和睾酮替代治疗对2型糖尿病伴性腺功能减退患者继发性红细胞增多的影响

性腺功能减退通常与2型糖尿病（T2DM）有关，睾酮替代疗法（TRT）是一种关键的治疗选择。钠葡萄糖共转运蛋白-2抑制剂（SGLT-2i）类是T2DM治疗的一部分。两种治疗均可增加Hct、Hb和RBC水平，并有继发性红细胞增多的潜在风险。本研究比较了接受和不接受SGLT-2i和TRT治疗性腺功能减退的T2DM患者的Hct、RBC和Hb的变化。方法分析2015-2023年Clalit医疗服务中心收治的男性T2DM性腺功能减退患者的数据。混合线性回归评估SGLT-2i对Hct、Hb和RBC水平的影响，而广义估计方程用于预测Hct患者比例（54%）。结果共有5235例男性患者符合纳入标准，其中3146例为SGLT-2i（+）组，2089例为SGLT-2i（−）组。平均年龄63.8±11.0岁，平均Hct为43.3%±4.4%，BMI为30.8±5.2 kg/m2， eGFR为84.9±19.3 mL/min/1.73m2。SGLT-2i（+）组在TRT启动后Hct、Hb和RBC有统计学意义的增加（p < 0.001）。而TRT启动后Hct总升高54%，OR = 1.85 (95% CI 0.96-3.67), p = 0.06无统计学意义。然而，SGLT2i（+）组明显高于SGLT2i（-）组，OR = 4.85 [95% CI 3.06-7.69], p = 0.02。结论：SGLT-2i和TRT联合使用与T2DM患者继发性红细胞增多的几率增加有关。意识和潜在的治疗中断可以防止不必要的调查。经常监测这些参数是必不可少的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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