{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:07:17Z","timestamp":1790240837368,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council of Australia","id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Eli Lilly Alliance"},{"DOI":"10.13039\/501100025520","name":"Medical Research Future Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100025520","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015539","name":"Australian Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015539","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Polypharmacy in chronic kidney disease (CKD) is substantial. Clinicians and patients are often reluctant to add medications to already complex regimens, partly due to concerns about diminishing efficacy and increased adverse effects. We assessed whether the efficacy and safety of canagliflozin are modified by polypharmacy status in patients with type 2 diabetes (DM) and CKD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a post-hoc analysis of the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial, which evaluated the effects of canagliflozin on outcomes in patients with DM and CKD. Participants were categorized as no polypharmacy (0\u20134 medicines), polypharmacy (5\u20139 medicines) or hyperpolypharmacy (\u226510 medicines). We assessed the relative effects of canagliflozin on clinical and safety outcomes by polypharmacy status using Cox proportional hazards models. We assessed absolute benefits using Poisson regression. The primary outcome was a composite of doubling of serum creatinine, kidney failure, or death due to cardiovascular or kidney disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 4401 participants, 612 (14%), 2404 (55%) and 1385 (31%) were categorized as no polypharmacy, polypharmacy and hyperpolypharmacy, respectively. Mean number of medications was 8.3 (SD 3.77). The effect of canagliflozin on kidney and cardiovascular outcomes was consistent irrespective of polypharmacy status, with no interaction observed for safety outcomes (all P-interaction &amp;gt;.06). Rates of treatment discontinuation increased with medication burden, but were lower with canagliflozin versus placebo, regardless of polypharmacy status (P-interaction = .16). Incidence of all-cause hospitalization, and heart failure hospitalization or cardiovascular death increased with higher medication burden; thus absolute risk reductions were estimated to be substantially greater in patients with polypharmacy and hyperpolypharmacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Among patients with DM and CKD, the efficacy and safety of canagliflozin appear consistent regardless of polypharmacy status, with larger estimated absolute reductions in hospitalizations and cardiovascular events in those experiencing polypharmacy or hyperpolypharmacy. These findings suggest that polypharmacy alone should not preclude consideration of sodium glucose cotransporter 2 inhibitor therapy in patients with CKD and DM for whom treatment is otherwise indicated.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfag203","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:34:56Z","timestamp":1788521696000},"source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of canagliflozin are consistent across polypharmacy burden in CKD: insights from the CREDENCE trial"],"prefix":"10.1093","author":[{"given":"Emily K","family":"Yeung","sequence":"first","affiliation":[{"name":"Renal & Metabolic Division, The George Institute for Global Health, University of New South Wales , Sydney ,","place":["Australia"]},{"name":"Department of Nephrology, Royal Melbourne Hospital , Melbourne, Victoria 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W","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, School of Clinical Medicine, The University of Hong Kong ,","place":["Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sradha","family":"Kotwal","sequence":"additional","affiliation":[{"name":"Renal & Metabolic Division, The George Institute for Global Health, University of New South Wales , Sydney ,","place":["Australia"]},{"name":"Department of Nephrology, Prince of Wales Hospital , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9370-9913","authenticated-orcid":false,"given":"Clare","family":"Arnott","sequence":"additional","affiliation":[{"name":"Renal & Metabolic Division, The George Institute for Global Health, University of New South Wales , Sydney ,","place":["Australia"]},{"name":"St Vincent\u2019s Hospital , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeera","family":"Levin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, The University of British Columbia , Vancouver, British Columbia ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meg","family":"Jardine","sequence":"additional","affiliation":[{"name":"NHMRC Clinical Trials Centre, University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Department of Renal Medicine, Concord Repatriation and General Hospital , Sydney, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Kun","family":"Lim","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, University of Malaya , Kuala Lumpur 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