{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:34:40Z","timestamp":1793205280172,"version":"4.5.0"},"reference-count":33,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Intern Med"],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"\n Importance<\/jats:title>\n Hyperkalemia is a common complication of taking a renin-angiotensin-aldosterone system inhibitor (RAASi). Post hoc analyses of large randomized clinical trials suggested that the addition of sodium-glucose cotransporter 2 inhibitors (SGLT2i) may attenuate this risk. It is unknown if this observation extends to daily clinical practice.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the association between SGLT2i initiation and hyperkalemia in individuals receiving RAASi with a background of diabetes, heart failure, or chronic kidney disease.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This population-based retrospective cohort study was conducted in Ontario, Canada, from July 1, 2015, to June 30, 2021. The cohort comprised adults 66 years and older who were prescribed a RAASi and had a history of diabetes or heart failure, an estimated glomerular filtration rate of less than 45 mL\/min\/1.73 m\n 2<\/jats:sup>\n , and\/or a urine albumin to creatinine ratio of greater than 30 mg\/mmol. The data were analyzed between March 28, 2023, and March 22, 2024.\n <\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n The study exposure was a new prescription of an SGLT2i compared to noninitiation of an SGLT2i. Inverse probability of treatment weighting by a propensity score for the receipt of SGLT2i was used to achieve balance of baseline covariates in both exposure groups.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary study outcome was hyperkalemia, defined as a serum potassium of greater than 5.5 mEq\/L or an administrative code for an inpatient or outpatient encounter with hyperkalemia within 1 year of the index date.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 20\u202f063 individuals who initiated an SGLT2i (mean [SD] age, 76.9 [6.6] years; 12\u202f020 [59.9%] male) were compared to a pseudopopulation of 19\u202f781 nonusers (mean [SD] age, 76.8 [7.0] years; 11\u202f731 [59.3%] male). In the overall cohort, 95% had diabetes, 17% had heart failure, and 32% had stage 3 to 5 chronic kidney disease. SGLT2i initiation was associated with a lower risk of hyperkalemia (hazard ratio, 0.89 [95% CI, 0.82-0.96]). SGLT2i users had a significantly lower rate of RAASi discontinuation compared to nonusers (36% vs 45%;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This cohort study demonstrated that, among individuals with diabetes, heart failure, or chronic kidney disease who were receiving a RAASi, SGLT2i initiation was associated with a lower risk of hyperkalemia and RAASi discontinuation.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamainternmed.2025.0686","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T11:31:00Z","timestamp":1745839860000},"page":"827","source":"Crossref","is-referenced-by-count":32,"title":["SGLT2 Inhibitors and Risk for Hyperkalemia Among Individuals Receiving RAAS Inhibitors"],"prefix":"10.1001","volume":"185","author":[{"given":"Sara","family":"Wing","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, St Michael\u2019s Hospital, Toronto, Ontario, Canada"},{"name":"Department of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"Li Ka Shing Knowledge Institute, St Michael\u2019s Hospital, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel G.","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada"},{"name":"Institute for Clinical Evaluative Sciences, Ontario, Canada"},{"name":"Department of Medicine, St Michael\u2019s Hospital, University of Toronto, Toronto, Ontario, Canada"},{"name":"Department of Obstetrics and Gynaecology, St Michael\u2019s Hospital, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Yau","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"Li Ka Shing Knowledge Institute, St Michael\u2019s Hospital, Toronto, Ontario, Canada"},{"name":"Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada"},{"name":"University Health Network, Division of Nephrology, Department of Medicine, University of Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nivethika","family":"Jeyakumar","sequence":"additional","affiliation":[{"name":"Institute for Clinical Evaluative Sciences, Ontario, Canada"},{"name":"Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheikh","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Institute for Clinical Evaluative Sciences, Ontario, Canada"},{"name":"Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute for Clinical Evaluative Sciences, Ontario, Canada"},{"name":"Lawson Health Research Institute, London Health Sciences Centre, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Z. 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