{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:48:28Z","timestamp":1790995708851,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To conduct a pooled analysis of Phase 3 trials investigating the efficacy and safety of inclisiran across glycaemic and body mass index (BMI) strata.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Participants were randomized 1:1 to receive 300\u2009mg inclisiran sodium or placebo twice yearly, after initial and 3\u2010month doses up to 18\u2009months, with background oral lipid\u2010lowering therapy. Analyses were stratified by glycaemic status (normoglycaemia, prediabetes, and diabetes) or BMI (&lt;25, \u226525 to &lt;30, \u226530 to &lt;35, and \u226535\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ). Co\u2010primary endpoints were percentage and time\u2010adjusted percentage change in low\u2010density lipoprotein (LDL) cholesterol from baseline. Safety was also assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Baseline characteristics were balanced between treatment arms and across strata. Percent LDL cholesterol change (placebo\u2010corrected) with inclisiran from baseline to Day 510 ranged from \u221247.6% to \u221251.9% and from \u221248.8% to \u221254.4% across glycaemic\/BMI strata, respectively. Similarly, time\u2010adjusted percentage changes after Day 90 and up to Day 540 ranged from \u221246.8% to \u221252.0% and from \u221248.6% to \u221253.3% across glycaemic\/BMI strata, respectively. Inclisiran led to significant reductions in proprotein convertase subtilisin\/kexin type 9 and other atherogenic lipids and lipoproteins versus placebo across the glycaemic\/BMI strata. The proportions of individuals achieving LDL cholesterol thresholds of &lt;1.8\u2009mmol\/L and &lt;1.4\u2009mmol\/L with inclisiran increased with increasing glycaemic and BMI strata. Across the glycaemic\/BMI strata, a higher proportion of individuals had mild\/moderate treatment\u2010emergent adverse events (TEAEs) at the injection site with inclisiran (2.8%\u20137.7%) versus placebo (0.2%\u20132.1%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Inclisiran provided substantial and sustained LDL cholesterol lowering across glycaemic\/BMI strata, with a modest excess of transient mild\u2010to\u2010moderate TEAEs at the injection site.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15650","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T05:34:24Z","timestamp":1715924064000},"page":"3223-3237","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Inclisiran in individuals with diabetes or obesity: Post hoc pooled analyses of the\n                    <scp>ORION<\/scp>\n                    \u20109,\n                    <scp>ORION<\/scp>\n                    \u201010 and\n                    <scp>ORION<\/scp>\n                    \u201011 Phase 3 randomized trials"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1040-6229","authenticated-orcid":false,"given":"Lawrence A.","family":"Leiter","sequence":"first","affiliation":[{"name":"Li Ka Shing Knowledge Institute, St. Michael's Hospital University of Toronto  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick J.","family":"Raal","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences University of the Witwatersrand  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2954-0695","authenticated-orcid":false,"given":"Gregory G.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Division of Cardiology University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Koenig","sequence":"additional","affiliation":[{"name":"Deutsches Herzzentrum M\u00fcnchen Technische Universit\u00e4t M\u00fcnchen  Munich Germany"},{"name":"DZHK (German Centre for Cardiovascular Research) Partner Site Munich Heart Alliance  Munich Germany"},{"name":"Institute of Epidemiology and Medical Biometry University of Ulm  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0508-0954","authenticated-orcid":false,"given":"Kausik K.","family":"Ray","sequence":"additional","affiliation":[{"name":"Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health Imperial College  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Landmesser","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9 Charit\u00e9 University Medicine Berlin, Friede Springer Cardiovascular Prevention Center od Charit\u00e9, Berlin Institute of Health, DZHK, Partner Site Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackie","family":"Han","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena Garcia","family":"Conde","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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