SGLT2 inhibitor use is associated with more polycythemia vera diagnosis codes but not with JAK2-positive polycythemia vera: a propensity score–matched cohort study
5 affiliations
- 1Department of Internal Medicine A, Kaplan Medical Center, Rehovot and Faculty of Medicine, Hebrew University of Jerusalem
- 2Institute of Hematology and Blood Bank, Meir Medical Center, Kfar Saba and Gray Faculty of Medical and Health Sciences, Tel Aviv University
- 3Department of Cardiology, Kaplan Medical Center, Rehovot and Faculty of Medicine, Hebrew University of Jerusalem
- 4Intensive Care Unit, Kaplan Medical Center, Rehovot and Faculty of Medicine, Hebrew University of Jerusalem
- 5Department of Diabetes, Endocrinology, and Metabolic diseases, Wolfson Medical Center, Holon and Gray Faculty of Medical and Health Sciences, Tel Aviv University
Abstract
Background: Treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2is) is associated with modest increases in hematocrit, which may prompt hematologic evaluation. We examined whether SGLT2i use is associated with increased detection of previously unrecognized myeloproliferative neoplasms (MPNs) and compared diagnosis code–based with JAK2 -positive ascertainment of polycythemia vera (PV).
Methods: We conducted a retrospective cohort study using electronic health records from Clalit Health Services, including adults aged ≥40 years with diabetes who initiated SGLT2is or dipeptidyl peptidase-4 inhibitors (DPP4is) between January 2015 and July 2025, with follow-up through November 2025. Baseline clinical, laboratory, and medication data were collected, and participants were followed for incident MPNs. SGLT2i users were matched 1:1 to DPP4i users using propensity scores. Hazard ratios (HRs) were estimated using Cox and Fine–Gray competing-risk models.
Results: A total of 73,147 SGLT2i and 48,639 DPP4i users were eligible. After propensity score matching, 40,550 patients remained in each group, with balance across most baseline characteristics; residual creatinine imbalance was addressed in an extended model. Median follow-up was 3.8 years with SGLT2is and 7.0 years with DPP4is. A new PV diagnosis code (ICD-10 D45) was recorded in 204 SGLT2i users and 205 DPP4i users [1.22 vs. 0.76 per 1,000 person-years; adjusted HR (aHR) 1.69, 95% confidence interval (CI) 1.39–2.05], with the excess concentrated in the first year after initiation. Among the 204 patients who underwent JAK2 testing, 64 (31.4%) had a positive result, representing 15.6% of all 409 patients with a D45 code. JAK2 positivity among tested patients was lower with SGLT2is than DPP4is (24.5% vs. 37.7%). JAK2 -positive coded PV was identified in 24 and 40 patients, respectively (0.14 vs. 0.15 per 1,000 person-years; aHR 1.00, 95% CI 0.60–1.65). No significant differences were observed for essential thrombocythemia or primary myelofibrosis. Results were consistent in competing-risk and sensitivity analyses.
Conclusions: SGLT2i use was associated with more PV diagnosis codes but not with JAK2 -positive PV or other MPNs. The findings are consistent with increased diagnostic evaluation of SGLT2i-related erythrocytosis rather than increased occurrence of clonal PV. Diagnosis codes alone may substantially overestimate confirmed disease.
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BibTeX
@article{kirzhner2026sglt2,
title = {{SGLT2 inhibitor use is associated with more polycythemia vera diagnosis codes but not with JAK2-positive polycythemia vera: a propensity score–matched cohort study}},
author = {Alena Kirzhner and Martin Ellis and Maya Berla and Haitham abu Khadija and Hefziba Green and Dan Haberman and Meital Zikry Deitch and Tal Schiller},
journal = {Frontiers in Endocrinology},
year = {2026},
month = nov,
doi = {10.3389/fendo.2026.1979710},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1979710/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - SGLT2 inhibitor use is associated with more polycythemia vera diagnosis codes but not with JAK2-positive polycythemia vera: a propensity score–matched cohort study
AU - Alena Kirzhner
AU - Martin Ellis
AU - Maya Berla
AU - Haitham abu Khadija
AU - Hefziba Green
AU - Dan Haberman
AU - Meital Zikry Deitch
AU - Tal Schiller
PY - 2026
DA - 2026/11/03
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1979710
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1979710/full
AB - Background: Treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2is) is associated with modest increases in hematocrit, which may prompt hematologic evaluation. We examined whether SGLT2i use is associated with increased detection of previously unrecognized myeloproliferative neoplasms (MPNs) and compared diagnosis code–based with JAK2 -positive ascertainment of polycythemia vera (PV). Methods: We conducted a retrospective cohort study using electronic health records from Clalit Health Services, including adults aged ≥40 years with diabetes who initiated SGLT2is or dipeptidyl peptidase-4 inhibitors (DPP4is) between January 2015 and July 2025, with follow-up through November 2025. Baseline clinical, laboratory, and medication data were collected, and participants were followed for incident MPNs. SGLT2i users were matched 1:1 to DPP4i users using propensity scores. Hazard ratios (HRs) were estimated using Cox and Fine–Gray competing-risk models. Results: A total of 73,147 SGLT2i and 48,639 DPP4i users were eligible. After propensity score matching, 40,550 patients remained in each group, with balance across most baseline characteristics; residual creatinine imbalance was addressed in an extended model. Median follow-up was 3.8 years with SGLT2is and 7.0 years with DPP4is. A new PV diagnosis code (ICD-10 D45) was recorded in 204 SGLT2i users and 205 DPP4i users [1.22 vs. 0.76 per 1,000 person-years; adjusted HR (aHR) 1.69, 95% confidence interval (CI) 1.39–2.05], with the excess concentrated in the first year after initiation. Among the 204 patients who underwent JAK2 testing, 64 (31.4%) had a positive result, representing 15.6% of all 409 patients with a D45 code. JAK2 positivity among tested patients was lower with SGLT2is than DPP4is (24.5% vs. 37.7%). JAK2 -positive coded PV was identified in 24 and 40 patients, respectively (0.14 vs. 0.15 per 1,000 person-years; aHR 1.00, 95% CI 0.60–1.65). No significant differences were observed for essential thrombocythemia or primary myelofibrosis. Results were consistent in competing-risk and sensitivity analyses. Conclusions: SGLT2i use was associated with more PV diagnosis codes but not with JAK2 -positive PV or other MPNs. The findings are consistent with increased diagnostic evaluation of SGLT2i-related erythrocytosis rather than increased occurrence of clonal PV. Diagnosis codes alone may substantially overestimate confirmed disease.
SN - 1664-2392
ER -