{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:42:16Z","timestamp":1791978136882,"version":"4.4.0"},"reference-count":39,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100009457","name":"Region Sj\u00e6lland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009457","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Steno Diabetes Center Zealand"},{"DOI":"10.13039\/501100003035","name":"Aase og Ejnar Danielsens Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003035","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF19OC0058155"],"award-info":[{"award-number":["NNF19OC0058155"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Steno Diabetes Center Odense"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>To examine the effects of semaglutide on insulin sensitivity, insulin resistance, and \u03b2-cell function and explore whether these changes were mediated by weight loss in overweight or obese individuals with schizophrenia and prediabetes receiving second-generation antipsychotics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>In this 30-week, double-blind trial, 154 participants were randomized to semaglutide (n = 77) or placebo (n = 77); 141 (91.5%) completed the study. Baseline and end-of-study assessments included fasting glucose, insulin, C-peptide, HOMA2 of \u03b2-cell function, HOMA2 of insulin sensitivity, HOMA of insulin resistance, and body weight.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Participants (56% women, mean age 38.3 years) provided complete insulin data in 131 cases. Compared with placebo, semaglutide significantly reduced fasting glucose (\u22120.87 mmol\/L [95% CI \u22121.15, \u22120.59]; P &amp;lt; 0.001), improved insulin sensitivity (8.60 [5.82, 13.65]; P = 0.001), and lowered insulin resistance (\u22120.69 [\u22121.00, \u22120.20]; P = 0.006). Mean weight loss was 9.2 kg and mediated improvements in insulin sensitivity (estimate 7.82; P = 0.01) and insulin resistance (estimate \u22120.75; P = 0.01). Nonsignificant trends were observed toward reduced fasting insulin (\u221252.3 pmol\/L; P = 0.11) and C-peptide (\u2212182.9 pmol\/L; P = 0.096), with a modest, nonsignificant increase in \u03b2-cell function (8.10; P = 0.19).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Semaglutide significantly improved insulin sensitivity, reduced insulin resistance, lowered fasting glucose, and promoted substantial weight loss in patients with antipsychotic-induced metabolic disturbances. Weight loss partly mediated the metabolic improvements, while \u03b2-cell function remained largely unchanged. These findings support semaglutide as a potential strategy for mitigating metabolic dysfunction in this high-risk population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc25-2041","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T15:13:37Z","timestamp":1772637217000},"page":"800-807","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":3,"title":["Semaglutide Effects on Insulin Sensitivity and \u03b2-Cell Function in Patients With Schizophrenia, Prediabetes, and Obesity Treated With Second-Generation Antipsychotics: Findings From the HISTORI Trial, a 30-Week Randomized, Placebo-Controlled Trial With Semaglutide 1.0 mg Weekly"],"prefix":"10.2337","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2218-5045","authenticated-orcid":false,"given":"Ashok A.","family":"Ganeshalingam","sequence":"first","affiliation":[{"name":"Endocrine Research Unit, Department of Endocrinology, Odense University Hospital 1 , Odense, Denmark"},{"name":"Department of Clinical Research, Faculty of Health Science, University of Southern Denmark 2 , Odense, Denmark"},{"name":"Steno Diabetes Center Odense, Odense University Hospital 3 , Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Uhrenholt","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Faculty of Health Science, University of Southern Denmark 2 , Odense, Denmark"},{"name":"Research Unit for Clinical Psychopharmacology, Psychiatry West in Region Zealand 4 , Slagelse, Denmark"},{"name":"Child and Adolescent Psychiatry Odense, Mental Health Services in the Region of Southern Denmark 5 , Odense, Denmark"},{"name":"Psychiatric Research Unit, Copenhagen University Hospital\u2013Psychiatry Region Zealand 6 , Slagelse, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidse","family":"Arnfred","sequence":"additional","affiliation":[{"name":"Psychiatric Research Unit, Copenhagen University Hospital\u2013Psychiatry Region Zealand 6 , Slagelse, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen 7 , Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"G\u00e6de","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Geriatrics and Neurology, N\u00e6stved, Slagelse og Ringsted Sygehuse 8 , Slagelse, Denmark"},{"name":"IRS\u2013Department of Regional Health Research, Faculty of Health Science, University of Southern Denmark 9 , Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas K.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"OUH, OPEN\u2013Open Patient Data Explorative Network (Odense) 10 , Odense, 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