{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:44:12Z","timestamp":1782823452641,"version":"3.54.5"},"reference-count":21,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacy"],"abstract":"<jats:p>Background: Hyperkalemia (HK) is a common complication of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, and the risk is often increased by concomitant use of a mineralocorticoid receptor antagonist (MRA). The effect of SGLT2i co-prescription on this risk in routine clinical practice remains incompletely understood. Methods: This is a secondary analysis of a published retrospective cohort of 905 adult RAASi users attending outpatient clinics at King Abdulaziz Medical City, Jeddah, Saudi Arabia (IRB: NRJ22J\/279\/11), followed for a median of 28 months. Patients were classified as RAASi alone (n = 723) or RAASi plus MRA (n = 182). Beta-blockers and digoxin were excluded from the exposure definition. Effect modification by SGLT2i was assessed using logistic regression with a multiplicative interaction term. Results: MRA addition was associated with significantly higher rates of any HK (48.4% vs. 28.9%; RR 1.67, 95% CI 1.38\u20132.02, p &lt; 0.001) and moderate-to-severe HK (13.7% vs. 6.9%; RR 1.99, 95% CI 1.26\u20133.12, p = 0.003). Overall, RAASi discontinuation rates were similar between groups. SGLT2i co-prescription significantly modified the association between MRA use and HK-driven RAASi discontinuation (interaction p = 0.004): among patients without SGLT2i, MRA addition was associated with a more than 5-fold increase in HK-driven discontinuation (21.1% vs. 4.1%; RR 5.11, p = 0.001), whereas no significant excess risk was observed among SGLT2i users (1.8% vs. 4.2%; RR 0.44, 95% CI 0.12\u20131.57, p = 0.190), although this subgroup estimate was imprecise. CKD (aOR 2.16, 95% CI 1.56\u20132.99) and age \u2265 75 years (aOR 1.64, 95% CI 1.04\u20132.58) were the strongest independent predictors of HK. Conclusions: MRA addition to RAASi substantially increases HK burden, and SGLT2i co-prescription appears to protect against HK-driven RAASi discontinuation in combined RAASi\u2013MRA-treated patients. In patients with established indications for SGLT2i, co-prescription may confer the additional benefit of preserving RAASi continuity in the setting of MRA combination therapy.<\/jats:p>","DOI":"10.3390\/pharmacy14040091","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:01:17Z","timestamp":1782813677000},"page":"91","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sodium-Glucose Co-Transporter 2 Inhibitors and Hyperkalemia-Related Discontinuation of Renin-Angiotensin-Aldosterone System Inhibitors During Mineralocorticoid Receptor Antagonist Therapy: A Real-World Cohort Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1885-3709","authenticated-orcid":false,"given":"Abdullah Hashim","family":"Almalki","sequence":"first","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah 11481, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Jeddah 22384, Saudi Arabia"},{"name":"Nephrology Section, Department of Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah 11426, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nourah Abdulaziz","family":"Alorainan","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center, Jeddah 22384, Saudi Arabia"},{"name":"Nephrology Section, Department of Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah 11426, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhjah Abdulhakim","family":"Bukhari","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center, Jeddah 22384, Saudi Arabia"},{"name":"Nephrology Section, Department of Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah 11426, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahad Ali","family":"Dokhaikh","sequence":"additional","affiliation":[{"name":"Nephrology Section, Department of Medicine, King Fahad Hospital, Al-Baha 65732, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma Mohamed Abbas","family":"Quqandi","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center, Jeddah 22384, Saudi Arabia"},{"name":"Endocrinology Section, Department of Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah 11426, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reyan Hatem","family":"Merdad","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah 11481, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Jeddah 22384, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0133-8615","authenticated-orcid":false,"given":"Laila Fahad","family":"Sadagah","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah 11481, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Jeddah 22384, Saudi Arabia"},{"name":"Nephrology Section, Department of Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah 11426, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2020). 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