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SGLT2 Inhibitors and Risk for Hyperkalemia Among Individuals Receiving RAAS Inhibitors
Sara Wing1,2,3, Joel G Ray2,4,5,6,7,8, Kevin Yau2,3,4,9
1Division of Nephrology, Department of Medicine, St Michael's Hospital, Toronto, Ontario, Canada.
JAMA Internal Medicine
|April 28, 2025
Summary
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce hyperkalemia risk in patients taking renin-angiotensin-aldosterone system inhibitors (RAASi). This study confirms the benefit in real-world practice, also showing reduced RAASi discontinuation.
Area of Science:
- Nephrology
- Cardiology
- Endocrinology
Background:
- Hyperkalemia is a frequent complication for patients on renin-angiotensin-aldosterone system inhibitors (RAASi).
- Prior studies suggest sodium-glucose cotransporter 2 inhibitors (SGLT2i) may mitigate this risk.
- Real-world evidence on SGLT2i's effect on hyperkalemia in RAASi users is limited.
Purpose of the Study:
- To assess the association between initiating SGLT2i and the risk of hyperkalemia.
- To evaluate this association in patients with diabetes, heart failure, or chronic kidney disease on RAASi therapy.
Main Methods:
- Population-based retrospective cohort study in Ontario, Canada (2015-2021).
- Included adults aged 66+ prescribed RAASi with specific comorbidities or kidney function markers.
- Used inverse probability of treatment weighting to compare SGLT2i initiators vs. non-initiators.
Main Results:
- SGLT2i initiation was linked to a reduced risk of hyperkalemia (HR, 0.89; 95% CI, 0.82-0.96).
- Patients initiating SGLT2i had significantly lower rates of RAASi discontinuation (36% vs. 45%).
- The cohort predominantly included patients with diabetes (95%).
Conclusions:
- SGLT2i initiation is associated with a lower risk of hyperkalemia in patients on RAASi.
- This real-world evidence supports SGLT2i use for managing hyperkalemia risk.
- SGLT2i use may also help maintain RAASi therapy.
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