{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:37:12Z","timestamp":1792456632611,"version":"4.5.0"},"reference-count":29,"publisher":"American Diabetes Association","issue":"6","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"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":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Studies have demonstrated dose-dependent efficacy of glucagon-like peptide 1 receptor agonists for glycemic control and body weight. The aim of this trial was to characterize the dose-dependent effects of semaglutide (up to 16 mg\/week) in people with type 2 diabetes and overweight or obesity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>In this parallel-group, participant- and investigator-blinded, phase 2 trial, 245 individuals with type 2 diabetes and BMI \u226527 kg\/m2 on metformin were randomized to weekly semaglutide (2, 8, or 16 mg s.c.) or placebo for 40 weeks. Doses were escalated every 4 weeks, followed by a maintenance period. Dose modifications were not allowed. Primary and secondary efficacy end points included change from baseline to week 40 in HbA1c and body weight, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Estimated treatment difference between 16 and 2 mg was \u22120.3 percentage points (%-points) (95% CI \u22120.7 to 0.2; P = 0.245) for HbA1c change and \u22123.4 kg (\u22126.0 to \u22120.8; P = 0.011) for weight change for the treatment policy estimand and \u22120.5%-points (\u22121.0 to \u22120.1; P = 0.015) and \u22124.5 kg (\u22127.6 to \u22121.4; P = 0.004), respectively, for the hypothetical estimand. Dose-response modeling confirmed these findings. Treatment-emergent adverse events (AEs) and treatment discontinuations due to AEs, primarily gastrointestinal, were more frequent in the semaglutide 8 and 16 mg groups than in the 2 mg group. No severe hypoglycemic episodes were reported.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Higher semaglutide doses for type 2 diabetes and overweight or obesity provide modest additional glucose-lowering effect, with additional weight loss, at the expense of more AEs and treatment discontinuations. A study for evaluating high-dose semaglutide in obesity is currently underway.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc24-2425","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T16:59:04Z","timestamp":1746637144000},"page":"905-913","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":26,"title":["High-Dose Semaglutide (Up to 16 mg) in People With Type 2 Diabetes and Overweight or Obesity: A Randomized, Placebo-Controlled, Phase 2 Trial"],"prefix":"10.2337","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7706-4585","authenticated-orcid":false,"given":"Vanita R.","family":"Aroda","sequence":"first","affiliation":[{"name":"1Endocrinology, Diabetes, and Hypertension, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils B.","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"2Novo Nordisk A\/S, S\u00f8borg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharath","family":"Kumar","sequence":"additional","affiliation":[{"name":"3Biostatistics, Novo Nordisk Service Centre India Private Ltd., Bangalore, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7006-7401","authenticated-orcid":false,"given":"Ildiko","family":"Lingvay","sequence":"additional","affiliation":[{"name":"4Department of Internal Medicine\/Endocrinology and Peter O\u2019Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Sofie","family":"Laulund","sequence":"additional","affiliation":[{"name":"2Novo Nordisk A\/S, S\u00f8borg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9723-3876","authenticated-orcid":false,"given":"John B.","family":"Buse","sequence":"additional","affiliation":[{"name":"5Division of Endocrinology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"trial investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"2025052014523398200_B1","year":"2021"},{"key":"2025052014523398200_B2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0140-6736(23)01301-6","article-title":"Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021","volume":"402","author":"GBD 2021 Diabetes Collaborators","year":"2023","journal-title":"Lancet"},{"key":"2025052014523398200_B3","unstructured":"World Obesity Federation\n          . 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