{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T05:07:51Z","timestamp":1794028071642,"version":"4.8.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2024,2,6]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Sodium glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and the nonsteroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone all individually reduce cardiovascular, kidney, and mortality outcomes in patients with type 2 diabetes and albuminuria. However, the lifetime benefits of combination therapy with these medicines are not known.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We used data from 2 SGLT2i trials (CANVAS [Canagliflozin Cardiovascular Assessment] and CREDENCE [Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation]), 2 ns-MRA trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease]), and 8 GLP-1 RA trials to estimate the relative effects of combination therapy versus conventional care (renin-angiotensin system blockade and traditional risk factor control) on cardiovascular, kidney, and mortality outcomes. Using actuarial methods, we then estimated absolute risk reductions with combination SGLT2i, GLP-1 RA, and ns-MRA in patients with type 2 diabetes and at least moderately increased albuminuria (urinary albumin:creatinine ratio \u226530 mg\/g) by applying estimated combination treatment effects to participants receiving conventional care in CANVAS and CREDENCE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Compared with conventional care, the combination of SGLT2i, GLP-1 RA, and ns-MRA was associated with a hazard ratio of 0.65 (95% CI, 0.55\u20130.76) for major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). The corresponding estimated absolute risk reduction over 3 years was 4.4% (95% CI, 3.0\u20135.7), with a number needed to treat of 23 (95% CI, 18\u201333). For a 50-year-old patient commencing combination therapy, estimated major adverse cardiovascular event\u2013free survival was 21.1 years compared with 17.9 years for conventional care (3.2 years gained [95% CI, 2.1\u20134.3]). There were also projected gains in survival free from hospitalized heart failure (3.2 years [95% CI, 2.4\u20134.0]), chronic kidney disease progression (5.5 years [95% CI, 4.0\u20136.7]), cardiovascular death (2.2 years [95% CI, 1.2\u20133.0]), and all-cause death (2.4 years [95% CI, 1.4\u20133.4]). Attenuated but clinically relevant gains in event-free survival were observed in analyses assuming 50% additive effects of combination therapy, including for major adverse cardiovascular events (2.4 years [95% CI, 1.1\u20133.5]), chronic kidney disease progression (4.5 years [95% CI, 2.8\u20135.9]), and all-cause death (1.8 years [95% CI, 0.7\u20132.8]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>In patients with type 2 diabetes and at least moderately increased albuminuria, combination treatment of SGLT2i, GLP-1 RA, and ns-MRA has the potential to afford relevant gains in cardiovascular and kidney event-free and overall survival.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.123.067584","type":"journal-article","created":{"date-parts":[[2023,11,12]],"date-time":"2023-11-12T08:45:13Z","timestamp":1699778713000},"page":"450-462","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":368,"title":["Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria"],"prefix":"10.1161","volume":"149","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., H.J.L.H., R.A.F., C.A., B.N., V.P.)."},{"name":"Department of Renal Medicine, Royal North Shore Hospital, Sydney, Australia (B.L.N.)."},{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (B.L.N., B.L.C., S.D.S., M.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":true,"given":"Hiddo J.L.","family":"Heerspink","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, University of New South Wales, Sydney, Australia (B.L.N., H.J.L.H., R.A.F., C.A., B.N., V.P.)."},{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen, The Netherlands (H.J.L.H., P.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Vart","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen, The Netherlands (H.J.L.H., P.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4215-9218","authenticated-orcid":true,"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (B.L.N., B.L.C., S.D.S., M.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0885-1788","authenticated-orcid":true,"given":"Robert A.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, University of New South Wales, Sydney, Australia (B.L.N., H.J.L.H., R.A.F., C.A., B.N., V.P.)."}],"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., H.J.L.H., R.A.F., C.A., B.N., V.P.)."},{"name":"Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia (C.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8355-023X","authenticated-orcid":true,"given":"Julianna","family":"de Oliveira Costa","sequence":"additional","affiliation":[{"name":"Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, UNSW Sydney, Australia (J.d.O.C., M.O.F., S.-A.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6444-7272","authenticated-orcid":true,"given":"Michael O.","family":"Falster","sequence":"additional","affiliation":[{"name":"Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, UNSW Sydney, Australia (J.d.O.C., M.O.F., S.-A.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7137-6855","authenticated-orcid":true,"given":"Sallie-Anne","family":"Pearson","sequence":"additional","affiliation":[{"name":"Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, UNSW Sydney, Australia (J.d.O.C., M.O.F., S.-A.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3791-2148","authenticated-orcid":true,"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\/0000-0002-0490-7465","authenticated-orcid":true,"given":"Bruce","family":"Neal","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, University of New South Wales, Sydney, Australia (B.L.N., H.J.L.H., R.A.F., C.A., B.N., V.P.)."},{"name":"Department of Epidemiology and Biostatistics, Imperial College London, United Kingdom (B.N.)."}],"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\/0000-0003-1183-1267","authenticated-orcid":true,"given":"George","family":"Bakris","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Chicago, IL (G.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4257-7620","authenticated-orcid":true,"given":"Vlado","family":"Perkovic","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health, University of New South Wales, Sydney, Australia (B.L.N., H.J.L.H., R.A.F., C.A., B.N., V.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3698-9597","authenticated-orcid":true,"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (B.L.N., B.L.C., S.D.S., M.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0885-1953","authenticated-orcid":true,"given":"Muthiah","family":"Vaduganathan","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (B.L.N., B.L.C., S.D.S., M.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2022.06.013"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2337\/dci22-0034"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(21)00203-5"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)02074-8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab777"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.101163"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.2337\/dci23-0030"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2025845"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2110956"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30748-0"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.2215\/cjn.08900722"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.058929"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1509753"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.08.745"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001063"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad195"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14108"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14108"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(19)30066-X"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(18)30023-8"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(16)30267-4"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.0000000000000186"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1681\/asn.2022020207"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.057934"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14179"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-0294"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.057736"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc21-1113"},{"key":"e_1_3_3_32_2","unstructured":"National Institute for Health and Care Excellence. Finerenone for treating chronic kidney disease in type 2 diabetes. Technical appraisal guidance [TA877]. March 23 2023. Accessed September 1 2023. https:\/\/www.nice.org.uk\/guidance\/ta877"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.016835"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-0614"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018100971"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgph.0001467"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l5873"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfac198"},{"key":"e_1_3_3_39_2","unstructured":"ClinicalTrials.gov. Prevention of Cardiovascular and Diabetic Kidney Disease in Type 2 Diabetes (PRECIDENTD). Accessed September 1 2023. https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT05390892"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfad009"},{"key":"e_1_3_3_41_2","unstructured":"Novo Nordisk. Company announcement Novo Nordisk will stop the once-weekly injectable semaglutide kidney outcomes trial FLOW based on interim analysis. October 10 2023. Accessed October 10 2023. https:\/\/www.novonordisk.com\/news-and-media\/news-and-ir-materials\/news-details.html?id=166327"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.13731"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.123.067584","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:00:53Z","timestamp":1791968453000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.123.067584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,6]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,2,6]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.123.067584"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.123.067584","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,6]]},"assertion":[{"value":"2023-10-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}