{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:22:56Z","timestamp":1791411776872,"version":"4.3.3"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"25","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2018,12,18]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>LEADER trial (Liraglutide Effect and Action in Diabetes: Evaluation of CV Outcome Results) results demonstrated cardiovascular benefits for patients with type 2 diabetes mellitus at high cardiovascular risk on standard of care randomized to liraglutide versus placebo. The effect of glucagon-like peptide-1 receptor agonist liraglutide on cardiovascular events and all-cause mortality in patients with type 2 diabetes mellitus and chronic kidney disease is unknown. Liraglutide\u2019s treatment effects in patients with and without kidney disease were analyzed post hoc.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              Patients were randomized (1:1) to liraglutide or placebo, both in addition to standard of care. These analyses assessed outcomes stratified by baseline estimated glomerular filtration rate (eGFR; &lt;60 versus \u226560 mL\/min\/1.73 m\n              <jats:sup>2<\/jats:sup>\n              ) and baseline albuminuria. The primary outcome (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and secondary outcomes, including all-cause mortality and individual components of the primary composite outcome, were analyzed using Cox regression.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Overall, 2158 and 7182 patients had baseline eGFR &lt;60 or \u226560 mL\/min\/1.73 m\n              <jats:sup>2<\/jats:sup>\n              , respectively. In patients with eGFR &lt;60 mL\/min\/1.73 m\n              <jats:sup>2<\/jats:sup>\n              , risk reduction for the primary composite cardiovascular outcome with liraglutide was greater (hazard ratio [HR], 0.69; 95% CI, 0.57\u20130.85) versus those with eGFR \u226560 mL\/min\/1.73 m\n              <jats:sup>2<\/jats:sup>\n              (HR, 0.94; 95% CI, 0.83\u20131.07; interaction\n              <jats:italic>P<\/jats:italic>\n              =0.01). There was no consistent effect modification with liraglutide across finer eGFR subgroups (interaction\n              <jats:italic>P<\/jats:italic>\n              =0.13) and when analyzing eGFR as a continuous variable (interaction\n              <jats:italic>P<\/jats:italic>\n              =0.61). Risk reductions in those with eGFR &lt;60 versus \u226560 mL\/min\/1.73 m\n              <jats:sup>2<\/jats:sup>\n              were as follows: for nonfatal myocardial infarction, HR, 0.74; 95% CI, 0.55\u20130.99 versus HR, 0.93; 95% CI, 0.77\u20131.13; for nonfatal stroke, HR, 0.51; 95% CI, 0.33\u20130.80 versus HR, 1.07; 95% CI, 0.84\u20131.37; for cardiovascular death, HR, 0.67; 95% CI, 0.50\u20130.90 versus HR, 0.84; 95% CI, 0.67\u20131.05; for all-cause mortality, HR, 0.74; 95% CI, 0.60\u20130.92 versus HR, 0.90; 95% CI, 0.75\u20131.07. Risk reduction for the primary composite cardiovascular outcome was not different for those with versus without baseline albuminuria (HR, 0.83; 95% CI, 0.71\u20130.97; and HR, 0.92; 95% CI, 0.79\u20131.07, respectively; interaction\n              <jats:italic>P<\/jats:italic>\n              =0.36).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Liraglutide added to standard of care reduced the risk for major cardiovascular events and all-cause mortality in patients with type 2 diabetes mellitus and chronic kidney disease. These results appear to apply across the chronic kidney disease spectrum enrolled.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/\">https:\/\/www.clinicaltrials.gov\/<\/jats:ext-link>\n              . Unique identifier: NCT01179048.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.118.036418","type":"journal-article","created":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T19:02:41Z","timestamp":1545073361000},"page":"2908-2918","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":136,"title":["Effects of Liraglutide Versus Placebo on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease"],"prefix":"10.1161","volume":"138","author":[{"given":"Johannes F. E.","family":"Mann","sequence":"first","affiliation":[{"name":"Kuratorium f\u00fcr Dialyse Kidney Center, Munich, Germany (J.F.E.M.)."},{"name":"Department of Nephrology, Friedrich Alexander University of Erlangen, Germany (J.F.E.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Tulane University Health Sciences Center, School of Medicine, New Orleans, LA (V.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofri","family":"Mosenzon","sequence":"additional","affiliation":[{"name":"Diabetes Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel (O.M., I.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itamar","family":"Raz","sequence":"additional","affiliation":[{"name":"Diabetes Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel (O.M., I.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Goldman","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark (B.G., T.I., B.J.v.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Idorn","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark (B.G., T.I., B.J.v.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernt Johan","family":"von Scholten","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark (B.G., T.I., B.J.v.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil R.","family":"Poulter","sequence":"additional","affiliation":[{"name":"Imperial Clinical Trials Unit, Imperial College London, UK (N.R.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The LEADER Publication Committee on behalf of the LEADER Trial Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.12861\/jrip.2013.11"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014070714"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2009.09.014"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008121270"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.536"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-134-8-200104170-00007"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.4.421"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60739-3"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810177"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043545"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30104-3"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1470-0"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1203858"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615692"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1307684"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1305889"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501352"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603827"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607141"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12983"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-1850"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2017.4228"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.028268"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gft462"},{"key":"e_1_3_4_28_2","unstructured":"FDA. 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