Sodium-Glucose Cotransporter 2 Inhibitors, Erythrocytosis, and Thrombosis in Adults With Type 2 Diabetes
Authors' conclusion
In this cohort study of patients with type 2 diabetes, SGLT2i use was associated with a higher risk of erythrocytosis compared with DPP-4is and GLP-1RAs; however, erythrocytosis was not associated with thrombotic events. These findings provide important reassurance regarding the safety of SGLT2i-induced erythrocytosis.
Study context
- Population
- Adults ≥18 years with T2D initiating SGLT2i, DPP-4i or GLP-1 RA, Israel's largest health care organization, January 1, 2015–June 30, 2024two matched cohorts
- Exposure
- SGLT2i initiation vs DPP-4i or GLP-1 RA initiation
- Outcome
- Erythrocytosis within 1 year of initiating SGLT2is; arterial and venous thrombotic events until end of follow-up
- Follow-up
- 1 year
Methodological detailspropensity score-matched, active-comparator, new-user design, 1:1 matching
- Propensity score-matched
- Active-comparator
- New-user design
- 1:1 matching
Main finding
As reported in the abstract
Increase in erythrocytosis prevalence, SGLT2i vs DPP-4i cohort (137 552 adults; 68 776 pairs)
5.5%
95% CI 5.1%–5.8%
Increase in erythrocytosis prevalence, SGLT2i vs GLP-1RA cohort (131 512 adults; 65 756 pairs)
5.8%
95% CI 5.4%–6.2%
Observational data: associations, not effects.
Further findings
Risk factors for erythrocytosis
| aOR (95% CI) | ||
|---|---|---|
| Male sex | 4.12 (3.80–4.48) | |
| Smoking | 2.00 (1.85–2.16) | |
| 0.20.5125Adjusted odds ratio (log scale) |
| Outcome | aOR (95% CI) | |
|---|---|---|
| Risk factors for erythrocytosisEmpagliflozinvs Dapagliflozin | 1.16 (1.09–1.25) | |
| 0.512Adjusted odds ratio (log scale) |
Hemoglobin and hematocrit increase, SGLT2i vs GLP-1RA cohort
- Hemoglobin increase
- 0.37 g/dL (95% CI, 0.36-0.38 g/dL)
- Hematocrit increase
- 1.50% (95% CI, 1.48%-1.53%)
Safety
Thrombotic events with new-onset erythrocytosis · until end of follow-up
| HR (95% CI) | ||
|---|---|---|
| New-onset erythrocytosisMI · time-varying Cox models | 0.92 (0.58–1.44) | |
| New-onset erythrocytosisVTE · time-varying Cox models | 1.56 (0.68–3.60) | |
| New-onset erythrocytosisStroke · time-varying Cox models | 1.26 (0.84–1.90) | |
| 0.20.5125Hazard ratio (log scale) |
Original publication
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