SGLT2 inhibitor use is associated with a reduced risk of hyperkalemia and lower rates of renin-angiotensin-aldosterone system inhibitor (RAASi) discontinuation in high-risk patients, according to a large population-based study.
Hyperkalemia is a frequent complication of RAASi therapy, particularly in individuals with diabetes, heart failure , or chronic kidney disease (CKD), often leading to treatment interruptions. While earlier clinical trials suggested sodium-glucose cotransporter 2 inhibitors (SGLT2i) might mitigate this risk, real-world evidence remained limited. This retrospective cohort study analysed 20,063 SGLT2i users and 19,781 matched nonusers aged ≥66 years in Ontario, Canada, all prescribed RAASi between 2015–2021. Participants had diabetes (95%), heart failure (17%), or CKD (32%), with outcomes assessed over one year.
SGLT2i initiation was linked to a 11% lower hyperkalemia risk (hazard ratio 0.89; 95% CI 0.82–0.96) and significantly reduced RAASi discontinuation rates (36% vs 45% in nonusers; P<0.001). These findings align with European data showing SGLT2i users had 23% fewer hyperkalemia events than DPP-4i initiators (HR 0.77), and meta-analyses demonstrating consistent risk reductions across CKD stages and heart failure subgroups.
For clinicians, these results support prioritising SGLT2i in RAASi-treated patients at high hyperkalemia risk, potentially improving adherence to cardiorenal therapies. Widespread SGLT2i adoption could help maintain guideline-directed RAASi use, reducing cardiovascular and renal complications in vulnerable populations.
Reference
Wing S et al. SGLT2 Inhibitors and risk for hyperkalemia among individuals receiving RAAS inhibitors. JAMA Intern Med. 2025;DOI:10.1001/jamainternmed.2025.0686.
