SGLT2 inhibitors and secondary polycythemia: a systematic review and meta-analysis of hematologic effects in patients with type 2 diabetes
In brief
SGLT2 inhibitors boost hematocrit by 2.3% and cause polycythemia in ~10%
A meta-analysis of ten studies found that SGLT2 inhibitors raise hematocrit by about 2.3 percentage points and hemoglobin by roughly half a gram per deciliter, with real-world data showing polycythemia prevalence climbing from 2.4% to 9.7% of patients. The rise appears early, reverses after stopping the drug, and may increase thrombotic risk, so clinicians should monitor patients at risk while awaiting larger outcome studies.
- Journal
- European journal of clinical pharmacology (Q2)
- Published
- 13 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Elrazi Awadelkarim Hamid Ali, Marrita Rabadi, Ruba Adel Aweer, Eihab Subahi, Elabbass A Abdelmahmuod, Awni Alshurafa, et al.
- PMID
- 42587114
- DOI
- 10.1007/s00228-026-04160-1
Why clinicians should know about it
- Picked for Pharmacology (medical) (top studies of the week, 16 August 2026).
Abstract
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used in the management of type 2 diabetes mellitus (T2DM) due to their survival benefits. However, these agents are associated with increases in hemoglobin (Hgb) and hematocrit (Hct), raising concern for secondary polycythemia or erythrocytosis and potential thrombotic risk. The clinical significance of these hematologic changes remains unclear. METHODS: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines. PubMed, Scopus, and Embase were searched up to February 2026 for studies evaluating the effect of SGLT2 inhibitors on hematologic parameters in adults with T2DM. Patients with primary polycythemia, end-stage renal disease (ESRD), or heart failure were excluded. Primary outcomes were changes in Hgb and Hct. Secondary outcomes included the incidence of erythrocytosis/polycythemia and thrombotic events. RESULTS: A total of 10 studies met inclusion criteria, comprising randomized and observational studies, with follow-up ranging from 8 weeks to 24 months. SGLT2 inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, were consistently associated with increases in Hgb and Hct. Across three randomized controlled trials, SGLT2 inhibitors significantly increased hematocrit (3 studies, 171 patients, pooled mean difference + 2.29%, 95% CI 1.48 to 3.09) and hemoglobin (3 studies, 171 patients, pooled mean difference + 0.51 g/dL, 95% CI 0.28 to 0.74) compared with placebo. Real-world data (9,646 patients) reported an increase in polycythemia prevalence from 2.4% to 9.7%, with severe cases in 1.4% of patients. Limited data suggested a potential association with thrombotic events, with one observational study of 100 patients with JAK2-unmutated erythrocytosis reporting a 10% event rate. Hematologic changes were observed early after treatment initiation and appeared reversible following drug discontinuation. CONCLUSIONS: In patients with type 2 diabetes, ESRD, or heart failure, SGLT2 inhibitor use is associated with consistent increases in hemoglobin and hematocrit. Although these effects may contribute to cardiovascular benefit, a subset of patients may develop clinically significant erythrocytosis. Clinicians should be aware of this potential effect and monitor high-risk individuals. Larger prospective studies are needed to better define the clinical significance of these findings.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.