{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:24:47Z","timestamp":1792070687957,"version":"4.4.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2022,5,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Hyperkalemia increases risk of cardiac arrhythmias and death and limits the use of renin-angiotensin-aldosterone system inhibitors and mineralocorticoid receptor antagonists, which improve clinical outcomes in people with chronic kidney disease or systolic heart failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of cardiorenal events in people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease. However, their effect on hyperkalemia has not been systematically evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>A meta-analysis was conducted using individual participant data from randomized, double-blind, placebo-controlled clinical outcome trials with SGLT2 inhibitors in people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease in whom serum potassium levels were routinely measured. The primary outcome was time to serious hyperkalemia, defined as central laboratory\u2013determined serum potassium \u22656.0 mmol\/L, with other outcomes including investigator-reported hyperkalemia events and hypokalemia (serum potassium \u22643.5 mmol\/L). Cox regression analyses were performed to estimate treatment effects from each trial with hazards ratios and corresponding 95% CIs pooled with random-effects models to obtain summary treatment effects, overall and across key subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Results from 6 trials were included comprising 49\u2009875 participants assessing 4 SGLT2 inhibitors. Of these, 1754 participants developed serious hyperkalemia, and an additional 1119 investigator-reported hyperkalemia events were recorded. SGLT2 inhibitors reduced the risk of serious hyperkalemia (hazard ratio, 0.84 [95% CI, 0.76\u20130.93]), an effect consistent across studies (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>heterogeneity<\/jats:sub>\n                      =0.71). The incidence of investigator-reported hyperkalemia was also lower with SGLT2 inhibitors (hazard ratio, 0.80 [95% CI, 0.68\u20130.93];\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>heterogeneity<\/jats:sub>\n                      =0.21). Reductions in serious hyperkalemia were observed across a range of subgroups, including baseline kidney function, history of heart failure, and use of renin-angiotensin-aldosterone system inhibitor, diuretic, and mineralocorticoid receptor antagonist. SGLT2 inhibitors did not increase the risk of hypokalemia (hazard ratio, 1.04 [95% CI, 0.94\u20131.15];\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>heterogeneity<\/jats:sub>\n                      =0.42).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>SGLT2 inhibitors reduce the risk of serious hyperkalemia in people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease without increasing the risk of hypokalemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.121.057736","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T14:08:51Z","timestamp":1649426931000},"page":"1460-1470","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":278,"title":["Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Hyperkalemia in People With Type 2 Diabetes: A Meta-Analysis of Individual Participant Data From Randomized, Controlled Trials"],"prefix":"10.1161","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-8380","authenticated-orcid":true,"given":"Brendon L.","family":"Neuen","sequence":"first","affiliation":[{"name":"The George Institute for Global Health, University of New South Wales, Sydney, Australia (B.L.N., C.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Oshima","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Laboratory Medicine, Kanazawa University, Japan (M.O., T.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-7100","authenticated-orcid":true,"given":"Rajiv","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine and VA Medical Center, Indianapolis (R.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9370-9913","authenticated-orcid":true,"given":"Clare","family":"Arnott","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, University of New South Wales, Sydney, Australia (B.L.N., C.A.)."},{"name":"Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia (C.A.)."},{"name":"Sydney Medical School, University of Sydney, Australia (C.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4164-0429","authenticated-orcid":true,"given":"David Z.","family":"Cherney","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Physiology, Division of Nephrology, University Health Network, University of Toronto, Ontario, Canada (D.Z.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Edwards","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC, Raritan, NJ (R.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Langkilde","sequence":"additional","affiliation":[{"name":"AstraZeneca, Gothenburg, Sweden (A.M.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth W.","family":"Mahaffey","sequence":"additional","affiliation":[{"name":"Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6412-7989","authenticated-orcid":true,"given":"Darren K.","family":"McGuire","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, and Parkland Health and Hospital System, Dallas (D.K.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0490-7465","authenticated-orcid":true,"given":"Bruce","family":"Neal","sequence":"additional","affiliation":[{"name":"The Charles Perkins Centre, University of Sydney, Australia (B.N.)."},{"name":"Department of Epidemiology and Biostatistics, Imperial College London, UK (B.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4257-7620","authenticated-orcid":true,"given":"Vlado","family":"Perkovic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of New South Wales, Sydney, Australia (V.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annpey","family":"Pong","sequence":"additional","affiliation":[{"name":"Merck &amp; Co Inc, Kenilworth, NJ (A.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0691-3359","authenticated-orcid":true,"given":"Marc S.","family":"Sabatine","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.S.S., S.D.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0209-4453","authenticated-orcid":true,"given":"Itamar","family":"Raz","sequence":"additional","affiliation":[{"name":"Diabetes Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Israel 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