Background: Analyses of prospective trials consistently demonstrated that therapy with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in type 2 diabetes (T2D) results in mild but significant increase in hematocrit (Hct) . We sought to determine if SGLT-2i therapy poses risk of erythrocytosis (ERY) in routine clinical practice.

Methods: This was a retrospective study of T2D US Veterans who were prescribed an SGLT-2i and had adequate adherence based on the proportion of days covered >80% during 3/2013-12/2019 and baseline Hct<50%. ERY incidence was defined as first Hct>54% within 180 days of an SGLT-2i initiation. The detailed patient data were obtained using the VA Informatics and Computing Infrastructure (VINCI) database. Odds ratio (OR) of ERY risk was calculated by logistic regression models adjusted for case-mix.

Results: We identified 9402 patients (76.0% Whites/14.7% Blacks) with baseline mean±SD age 65.0±8.9 yrs, BMI 34.1±6.3 kg/m2, Hct 41.5±4.1 % and hemoglobin A1c 8.5±1.2 %. By the end of observation period, mean Hct increased from the baseline by 1.74% [95% CI 1.68-1.80] in the entire cohort and 61 patients (0.65% of the cohort) developed ERY. We found that BMI, tobacco use, or obstructive sleep apnea (OSA) were not associated with risk of developing ERY. However, concomitant use of testosterone replacement therapy (TRT) was associated with significant ERY risk compared with SGLT-2i users not on TRT in both unadjusted analyses (OR 12.28 [95% CI 5.29-25.10]) and after adjustments for age, race, BMI, OSA, and tobacco use (OR 7.26 [95% CI 2.95-16.04]) . The risk of ERY was independent of baseline Hct or modality of TRT (topical vs. injectable) .

Conclusions: For the first time, we demonstrated that SGLT-2i initiation in men with T2D in real world clinical setting can result in detectable risk of erythrocytosis. It appears that concomitant TRT can significantly influence that risk. We recommend monitoring for Hct changes following SGLT-2i initiation and, particularly, in those persons who receive testosterone therapy.


A. R. Gosmanov: Research Support; AbbVie Inc., Kowa Research Institute, Inc., Speaker’s Bureau; AstraZeneca. D. E. Gemoets: None. M. A. Green: None. K. Schumacher: None.

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