{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:30:38Z","timestamp":1790137838667,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,6,10]],"date-time":"2018-06-10T00:00:00Z","timestamp":1528588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To assess the efficacy and safety of semaglutide, a recently approved glucagon\u2010like peptide 1 receptor agonist (GLP\u20101 RA) for type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We searched major electronic databases and grey literature sources for randomized controlled trials comparing semaglutide with placebo or other antidiabetic agents. Primary outcome was change from baseline in HbA1c. Secondary endpoints included change from baseline in body weight, blood pressure, heart rate and incidence of hypoglycaemia, gastrointestinal adverse effects, pancreatitis and diabetic retinopathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 6 placebo\u2010controlled and 7 active\u2010controlled studies with subcutaneous semaglutide were included. We identified only 1 trial with oral semaglutide. Compared with placebo, subcutaneous semaglutide 0.5 and 1 mg reduced HbA1c by 1.01% (95% CI, 0.56\u20101.47) and 1.38% (1.05\u20101.70), respectively. Both doses demonstrated superior glycaemic efficacy compared to other antidiabetic agents, including sitagliptin, exenatide, liraglutide, dulaglutide and insulin glargine. Semaglutide also had a beneficial effect on body weight (mean difference vs placebo \u22124.11 kg, 95% CI \u22124.85 to \u22123.37 for semaglutide 1 mg) and systolic blood pressure. We did not observe increased hypoglycaemia rates with semaglutide; nevertheless, we noted an increased incidence of nausea, vomiting and diarrhoea. Cases of pancreatitis were infrequent and the odds ratio for diabetic retinopathy compared with placebo was 1.32 (95% CI, 0.98\u20101.77).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Semaglutide is a potent once\u2010weekly GLP\u20101 RA, significantly reducing HbA1c, body weight and systolic blood pressure. However, it is associated with increased incidence of gastrointestinal adverse events. Results for pancreatitis and retinopathy require further assessment in post\u2010approval pharmacovigilance studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13361","type":"journal-article","created":{"date-parts":[[2018,5,13]],"date-time":"2018-05-13T22:09:55Z","timestamp":1526249395000},"page":"2255-2263","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":135,"title":["Semaglutide for type 2 diabetes mellitus: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0968-1039","authenticated-orcid":false,"given":"Panagiotis","family":"Andreadis","sequence":"first","affiliation":[{"name":"Clinical Research and Evidence\u2010Based Medicine Unit, Second Medical Department Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5242-0574","authenticated-orcid":false,"given":"Thomas","family":"Karagiannis","sequence":"additional","affiliation":[{"name":"Clinical Research and Evidence\u2010Based Medicine Unit, Second Medical Department Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5134-2401","authenticated-orcid":false,"given":"Konstantinos","family":"Malandris","sequence":"additional","affiliation":[{"name":"Clinical Research and Evidence\u2010Based Medicine Unit, Second Medical Department Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2232-1342","authenticated-orcid":false,"given":"Ioannis","family":"Avgerinos","sequence":"additional","affiliation":[{"name":"Clinical Research and Evidence\u2010Based Medicine Unit, Second Medical Department Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3261-2979","authenticated-orcid":false,"given":"Aris","family":"Liakos","sequence":"additional","affiliation":[{"name":"Clinical Research and Evidence\u2010Based Medicine Unit, Second Medical Department Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1055-0324","authenticated-orcid":false,"given":"Apostolos","family":"Manolopoulos","sequence":"additional","affiliation":[{"name":"Clinical Research and Evidence\u2010Based Medicine Unit, Second Medical Department Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9975-3835","authenticated-orcid":false,"given":"Eleni","family":"Bekiari","sequence":"additional","affiliation":[{"name":"Clinical Research and Evidence\u2010Based Medicine Unit, Second Medical Department Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9028-2328","authenticated-orcid":false,"given":"David R","family":"Matthews","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes, Endocrinology and Metabolism Churchill Hospital  Oxford UK"},{"name":"Harris Manchester College University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0221-4072","authenticated-orcid":false,"given":"Apostolos","family":"Tsapas","sequence":"additional","affiliation":[{"name":"Clinical Research and Evidence\u2010Based Medicine Unit, Second Medical Department Aristotle University of Thessaloniki  Thessaloniki Greece"},{"name":"Harris Manchester College University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,10]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"Food and Drug Administration (FDA). OZEMPIC (semaglutide) injection for subcutaneous use. Initial U.S. Approval: 2017.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/209637lbl.pdf. Accessed January 15 2018."},{"key":"e_1_2_6_3_1","unstructured":"European Medicines Agency (EMA). Summary of opinion (inital authorisation). Ozempic: Semaglutide 0.5 mg and 1 mg.2017.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Summary_of_opinion\u2010Initial_authorisation\/human\/004174\/WC500240373.pdf. Accessed February 20 2018."},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.14752"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30013-X"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30092-X"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-0417"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30085-2"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(18)30024-X"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607141"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000100"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13172"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603827"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-1210"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2017-000475"},{"key":"e_1_2_6_16_1","unstructured":"2016 JPT Higgins JAC Sterne J Savovi\u0107 A revised tool for assessing risk of bias in randomized trials"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7109.629"},{"key":"e_1_2_6_18_1","unstructured":"HigginsJPT GreenS. Cochrane Handbook for systematic reviews of interventions: imputing standard deviations for changes from baseline.2011http:\/\/handbook\u20105\u20101.cochrane.org\/chapter_16\/16_1_3_2_imputing_standard_deviations_for_changes_from_baseline.htm. Accessed January 15 2018."},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-147-8-200710160-00182"},{"key":"e_1_2_6_20_1","unstructured":"RyanRCochrane Consumers and Communication Review Group. Heterogeneity and subgroup analyses in Cochrane Consumers and Communication Group reviews: planning the analysis at protocol stage.2016.http:\/\/cccrg.cochrane.org\/sites\/cccrg.cochrane.org\/files\/public\/uploads\/heterogeneity_subgroup_analyses_revising_december_1st_2016.pdf. Accessed January 15 2018."},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4289-0"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0165"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13082"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13218"},{"key":"e_1_2_6_25_1","unstructured":"RodbardHL ReedJ de laRoseR et al. Efficacy and safety of semaglutide once\u2010weekly vs placebo as add\u2010on to basal insulin alone or in combination with metformin in subjects with type 2 diabetes (SUSTAIN 5). Paper presented at: EASD 2016;Munich Germany."},{"key":"e_1_2_6_26_1","unstructured":"HigginsJPT GreenS. Cochrane handbook for systematic reviews of interventions: imputing standard deviations for changes from baseline. Recommendations on testing for funnel plot asymmetry.2011.http:\/\/handbook\u20105\u20101.cochrane.org\/chapter_10\/10_4_3_1_recommendations_on_testing_for_funnel_plot_asymmetry.htm. Accessed April 24 2018."},{"key":"e_1_2_6_27_1","unstructured":"Food and Drug Administration (FDA). Endocrinologic and Metabolic Drugs Advisory Committee Meeting new drug application (NDA) 209637 for semaglutide.2017.https:\/\/www.fda.gov\/downloads\/advisorycommittees\/committeesmeetingmaterials\/drugs\/endocrinologicandmetabolicdrugsadvisorycommittee\/ucm580460.pdf. Accessed January 19 2018."},{"key":"e_1_2_6_28_1","article-title":"A systematic literature review and network meta\u2010analysis comparing once\u2010weekly semaglutide with other GLP\u20101 receptor agonists in patients with type 2 diabetes previously receiving 1\u20132 oral anti\u2010diabetic drugs","author":"Witkowski M","year":"2018","journal-title":"Diabetes Ther."},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13331"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12849"},{"key":"e_1_2_6_31_1","unstructured":"ClinicalTrials.gov. Identifier: NCT02906930. Efficacy and safety of oral semaglutide versus placebo in subjects with type 2 diabetes mellitus treated with diet and exercise only (PIONEER 1).2016.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02906930. Accessed January 19 2018."},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2012-001986"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq271"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.032038"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.13361","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.13361","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T05:48:23Z","timestamp":1761889703000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.13361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,10]]},"references-count":35,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1111\/dom.13361"],"URL":"https:\/\/doi.org\/10.1111\/dom.13361","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,10]]},"assertion":[{"value":"2018-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}