{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:10:29Z","timestamp":1792188629159,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Evaluate the effects of once\u2010weekly subcutaneous semaglutide 2.4 mg on cardiometabolic risk factors in people with overweight\/obesity without diabetes in the STEP 1 and 4 trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      STEP 1 and 4 were phase III, 68\u2010week, placebo\u2010controlled trials of once\u2010weekly semaglutide 2.4\u00a0mg combined with lifestyle intervention; STEP 4 had a 20\u2010week semaglutide run\u2010in and 48\u2010week randomized withdrawal period. Participants had a body mass index \u226530\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      or \u226527\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      with one or more weight\u2010related comorbidity, without diabetes. Pre\u2010specified endpoints were changes in waist circumference, systolic\/diastolic blood pressure (SBP\/DBP), lipids, fasting plasma glucose (FPG), fasting serum insulin and antihypertensive\/lipid\u2010lowering medication use. Post\u2010hoc assessments included non\u2010high\u2010density lipoprotein (HDL) cholesterol, homeostatic model assessment of insulin resistance (HOMA\u2010IR; STEP 1 only), atherosclerotic cardiovascular disease (ASCVD) risk (American College of Cardiology\/American Heart Association algorithm; STEP 1 only) and cardiometabolic risk factors by weight loss achieved (&lt;5%, 5% to &lt;10%, 10% to &lt;15%, or \u226515%) (STEP 1 only).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 1961 participants in STEP 1 and 803 in STEP 4, most had one or more complication\/comorbidity at baseline, with dyslipidaemia and hypertension most prevalent. In STEP 1, reductions in waist circumference, SBP, DBP, FPG, fasting serum insulin, lipids and HOMA\u2010IR were greater with semaglutide versus placebo (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u2009.001). Reductions in SBP, non\u2010HDL cholesterol, low\u2010density lipoprotein cholesterol and FPG were generally greater with semaglutide than placebo within weight\u2010loss categories. Non\u2010significant ASCVD risk reductions were observed with semaglutide versus placebo (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u2009.05). In STEP 4, improvements in waist circumference, SBP, FPG, fasting serum insulin and lipids during the semaglutide run\u2010in (week 0\u201020) were maintained over week 20\u201068 with continued semaglutide, but deteriorated following the switch to placebo (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001 [week 20\u201068]). Net reductions in antihypertensive\/lipid\u2010lowering medication use occurred with semaglutide versus placebo (both trials).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Semaglutide may improve cardiometabolic risk factors and reduce antihypertensive\/lipid\u2010lowering medication use versus placebo in adults with overweight\/obesity without diabetes. These potential benefits were not maintained after treatment discontinuation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      numbers\n                    <\/jats:title>\n                    <jats:p>STEP 1 NCT03548935, STEP 4 NCT03548987.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14890","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T05:12:33Z","timestamp":1665033153000},"page":"468-478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity:\n                    <scp>STEP<\/scp>\n                    1 and 4 exploratory analyses"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3750-9789","authenticated-orcid":false,"given":"Mikhail N.","family":"Kosiborod","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Disease Saint Luke's Mid America Heart Institute and University of Missouri\u2010Kansas City School of Medicine  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meena","family":"Bhatta","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9987-9371","authenticated-orcid":false,"given":"Melanie","family":"Davies","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre University of Leicester  Leicester UK"},{"name":"NIHR Leicester Biomedical Research Centre  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Deanfield","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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