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Oral semaglutide, the first oral GLP\u20101RA, has recently been approved for clinical use, based on the results of the randomized, Phase 3a Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) clinical trials. The PIONEER programme tested oral semaglutide in patients with T2D of duration ranging from 3.5 to 15\u2009years, from monotherapy through to insulin add\u2010on, in global populations and two trials dedicated to Japanese patients. Outcomes (glycated haemoglobin [HbA1c] and body weight reduction, plus other relevant efficacy and safety endpoints) were tested against both placebo and active standard\u2010of\u2010care medications. A separate trial evaluated the cardiovascular safety of oral semaglutide in patients with T2D at high cardiovascular risk. Over periods of treatment up to 78\u2009weeks, oral semaglutide 7 and 14\u2009mg once daily reduced HbA1c and body weight across the spectrum of T2D, and improved other diabetes\u2010related endpoints, such as fasting plasma glucose. Oral semaglutide provided significantly better efficacy than placebo and commonly used glucose\u2010lowering medications from the dipeptidyl peptidase\u20104 inhibitor (sitagliptin) and sodium\u2010glucose co\u2010transporter\u20102 inhibitor (empagliflozin) classes, as well as the subcutaneous GLP\u20101RAs liraglutide and dulaglutide. Oral semaglutide was well tolerated in line with the known safety profile of GLP\u20101RAs, with transient gastrointestinal events being the most common side effects reported. Cardiovascular safety was demonstrated for oral semaglutide in patients with cardiovascular disease or high cardiovascular risk. The results of the PIONEER programme suggest that oral semaglutide is efficacious and well tolerated for glycaemic control of T2D. The availability of oral semaglutide may help to broaden treatment choice and facilitate adoption of earlier GLP\u20101RA treatment in the paradigm of T2D management.<\/jats:p>","DOI":"10.1111\/dom.14054","type":"journal-article","created":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T06:02:10Z","timestamp":1586325730000},"page":"1263-1277","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":129,"title":["Efficacy, safety and cardiovascular outcomes of once\u2010daily oral semaglutide in patients with type 2 diabetes: The\n                    <scp>PIONEER<\/scp>\n                    programme"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6140-906X","authenticated-orcid":false,"given":"Tina K.","family":"Thethi","sequence":"first","affiliation":[{"name":"AdventHealth Translational Research Institute  Orlando Florida USA"}],"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\/0000-0002-5835-8019","authenticated-orcid":false,"given":"Juris J.","family":"Meier","sequence":"additional","affiliation":[{"name":"Diabetes Centre Bochum\u2010Hattingen, St Josef\u2010Hospital Ruhr\u2010University Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12591"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69705-5"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2012.11.008"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-019-05039-w"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-S009"},{"key":"e_1_2_8_7_1","unstructured":"European Medicines Agency. 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