Section of Endocrinology, Stratton VA Medical Center, 113 Holland Ave, Albany, 12208, USA.
Division of Endocrinology, Department of Medicine, Albany Medical College, Albany, NY, USA.
J Endocrinol Invest. 2024 Oct;47(10):2615-2621. doi: 10.1007/s40618-024-02350-1. Epub 2024 Mar 27.
In clinical trials, sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and testosterone replacement therapy (TRT) were shown to stimulate red blood cell production. Little is known if combination therapy poses risk of erythrocytosis in real world clinical practice.
This was a retrospective nationwide cohort study of US Veterans with type 2 diabetes (T2D) and baseline hematocrit between 38 and 50% who were prescribed SGLT-2i and/or TRT between 3/2013 and 10/2022 and had adequate adherence based on the proportion of days covered > 80%. Patients were divided into 3 groups: SGLT-2i only, TRT only, or combination therapy. Odds Ratio (OR) of new erythrocytosis defined as hematocrit level > 54% within 365 days of therapy initiation was calculated by logistic regression model adjusted for baseline hematocrit, age, BMI, obstructive sleep apnea, diuretic use, and smoking status.
Of the entire cohort of 53,971 people with T2D, total of 756 (1.4%) patients developed erythrocytosis. In unadjusted analyses, the OR of new onset erythrocytosis was higher in the combined SGLT-2i and TRT group compared with the SGLT-2i or TRT group alone (4.99, 95% CI (3.10-7.71) and 2.91, 95% CI (1.87-4.31), respectively). In the models adjusted for baseline characteristics, patients on combination therapy had significantly higher odds of erythrocytosis compared to those on SGLT-2i (OR 3.80, 95% CI (2.27-6.11)) or TRT alone (OR 2.49, 95% CI (1.51-3.59)). Testosterone delivery route (topical vs injectable) did not modify increased odds of erythrocytosis.
For the first time, we demonstrated that in large cohort of patients combined therapy with SGLT-2i and TRT is associated with increased erythrocytosis risk compared with either treatment alone. Given rising prevalence of SGLT-2i use, providers should consider periodic hematocrit assessment in persons receiving both SGLT-2i and TRT.
在临床试验中，钠-葡萄糖共转运蛋白-2 抑制剂（SGLT-2i）和睾酮替代疗法（TRT）被证明可刺激红细胞生成。在真实世界的临床实践中，尚不清楚联合治疗是否会增加红细胞增多症的风险。
这是一项回顾性的全美队列研究，纳入了 2013 年 3 月至 2022 年 10 月期间，使用 SGLT-2i 和/或 TRT 且基线血细胞比容在 38%至 50%之间的美国退伍军人，并且基于比例≥80%的天，药物的使用达到了足够的依从性。患者分为三组：仅 SGLT-2i 组、仅 TRT 组或联合治疗组。使用逻辑回归模型，根据基线血细胞比容、年龄、BMI、阻塞性睡眠呼吸暂停、利尿剂使用和吸烟状况，计算治疗开始后 365 天内新发生红细胞增多症（定义为血细胞比容水平>54%）的比值比（OR）。
在整个患有 2 型糖尿病（T2D）的 53971 名患者中，共有 756 名（1.4%）患者出现红细胞增多症。在未调整的分析中，与 SGLT-2i 或 TRT 单药组相比，联合 SGLT-2i 和 TRT 组新发红细胞增多症的 OR 更高（4.99，95%CI（3.10-7.71）和 2.91，95%CI（1.87-4.31））。在调整基线特征的模型中，与 SGLT-2i 组（OR 3.80，95%CI（2.27-6.11））或 TRT 组（OR 2.49，95%CI（1.51-3.59））相比，联合治疗组的红细胞增多症发生几率明显更高。睾酮的给药途径（局部 vs 注射）并没有改变红细胞增多症的几率。
我们首次证明，在大型患者队列中，与单独使用 SGLT-2i 或 TRT 相比，联合使用 SGLT-2i 和 TRT 治疗与红细胞增多症风险增加相关。鉴于 SGLT-2i 的使用日益普及，对于接受 SGLT-2i 和 TRT 联合治疗的患者，临床医生应考虑定期进行血细胞比容评估。
