{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:07:31Z","timestamp":1792699651669,"version":"4.5.0"},"reference-count":65,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"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":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Glucagon\u2010like peptide\u20101 receptor agonists improve glycaemic control: some are now available as oral and subcutaneous formulations, and some have indications for reducing cardiovascular risk. The expanded scope for these therapies warrants comprehensive safety evaluations. We\u00a0report the safety\/tolerability of subcutaneous and oral semaglutide from the SUSTAIN and PIONEER clinical trial programmes, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Adverse events (AEs) from 16 randomized placebo\u2010 or active\u2010controlled phase IIIa trials in patients with type 2 diabetes (n\u00a0=\u00a011\u2009159) including once\u2010weekly subcutaneous semaglutide (n\u00a0=\u00a03150; SUSTAIN trials) or once\u2010daily oral semaglutide (n\u00a0=\u00a04116; PIONEER trials) were analysed. Data pools were analysed for each programme, with separate analyses of cardiovascular outcomes trials (CVOTs; n\u00a0=\u00a06480).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the phase IIIa pools, gastrointestinal disorders were reported in 41.9%\/39.1% of patients with subcutaneous\/oral semaglutide, respectively (most prevalent during initiation\/escalation) versus 22.0%\/24.8% with comparators. Rates of kidney disorders, acute pancreatitis, malignant neoplasms, hypoglycaemia, diabetic retinopathy, heart failure and other cardiovascular events were similar for semaglutide versus comparators. Cholelithiasis incidence was higher with subcutaneous and oral semaglutide versus placebo. Diabetic retinopathy incidence was higher with subcutaneous semaglutide versus placebo in SUSTAIN 6. Small pulse rate increases occurred with both formulations; there was no increased rate of arrhythmias. Fatal AE incidence was similar between semaglutide and comparators. Versus placebo, CVOTs showed a reduced risk of major adverse cardiovascular events with subcutaneous semaglutide and non\u2010inferiority criteria were met with oral semaglutide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The most common AEs with semaglutide were gastrointestinal disorders, which decreased with continued therapy. These comprehensive safety\/tolerability data may better inform patient selection and guidance in care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14990","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T04:43:23Z","timestamp":1674708203000},"page":"1385-1397","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Safety and tolerability of semaglutide across the\n                    <scp>SUSTAIN<\/scp>\n                    and\n                    <scp>PIONEER<\/scp>\n                    phase\n                    <scp>IIIa<\/scp>\n                    clinical trial programmes"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7706-4585","authenticated-orcid":false,"given":"Vanita R.","family":"Aroda","sequence":"first","affiliation":[{"name":"Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umut","family":"Erhan","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Jelnes","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5835-8019","authenticated-orcid":false,"given":"Juris J.","family":"Meier","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gastroenterology, Hepatology and Diabetology Augusta Clinic  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten Tind","family":"Abildlund","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2912-1389","authenticated-orcid":false,"given":"Richard","family":"Pratley","sequence":"additional","affiliation":[{"name":"AdventHealth Translational Research Institute  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0456-6787","authenticated-orcid":false,"given":"Tina","family":"Vilsb\u00f8ll","sequence":"additional","affiliation":[{"name":"Clinical Research, Steno Diabetes Center Copenhagen  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-6739","authenticated-orcid":false,"given":"Mansoor","family":"Husain","sequence":"additional","affiliation":[{"name":"Ted Rogers Centre for Heart Research, Department of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12849"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-019-05039-w"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-S009"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(21)00203-5"},{"key":"e_1_2_10_6_1","unstructured":"European Medicines Agency.Ozempic\u00ae (semaglutide) European summary of product characteristics;2021https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/ozempic. 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