Endocrine Abstracts

Purpose of Study: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and testosterone replacement therapy (TRT) can increase red blood cell production through different mechanisms. Little is known if combination therapy poses risk of erythrocytosis (ERY) in real world clinical practice.

Methods: This was a retrospective nationwide cohort study of US Veterans with type 2 diabetes (T2D) without prior history of ERY who were prescribed SGLT-2i and/or TRT between 3/2013 – 10/2022, had no missing medical records data, 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. Odds Ratio (OR) of new ERY defined as hematocrit (Hct) level>54% within 365 days of therapy initiation was calculated by logistic regression model adjusted for case-mix. This study was approved by the IRB of Stratton VAMC, Albany, NY.

Results: Baseline clinical and biochemical characteristics were well balanced among the groups except higher rate of uncontrolled T2D in the SGLT-2i group and lower obstructive sleep apnea (OSA) prevalence in the TRT group (Table). Of the entire cohort, total of 732 (1.4%) patients developed ERY. In models adjusted for baseline Hct, age, BMI, OSA, diuretic use, and smoking status, patients on combination therapy had significantly higher odds of ERY compared to those on SGLT-2i (OR 3.86, 95% CI (2.35 – 6.12)) or TRT alone (OR 2.05, 95% CI (1.29 – 3.09)). The unadjusted ORs were comparable as well. The odds of developing ERY in each group were independent of baseline Hct.

Conclusions: For the first time, we demonstrated that in large cohort of patients combined therapy with SGLT-2i and TRT is associated with increased ERY risk compared with either treatment alone. Given rising prevalence of SGLT-2i use, providers should consider periodic Hct assessment in persons receiving both SGLT-2i and TRT.