{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:52:46Z","timestamp":1790265166254,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This meta-analysis aimed to evaluate the efficacy and safety of oral small-molecule glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes (T2D) and obesity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a meta-analysis of randomized controlled trials assessing the efficacy and safety of oral small-molecule GLP-1RAs in adults with T2D or obesity. A systematic literature search was conducted in databases including Web of Science, PubMed, Scopus, Google Scholar, Embase, and the Cochrane Library from database inception to March 2026. Continuous outcomes were summarized as mean differences (MDs), and dichotomous outcomes as risk ratios (RRs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ten studies were included. Oral small-molecule GLP-1RAs significantly reduced body weight (MD=-3.93, 95%CI:-4.78 to -3.09), body mass index (MD=-2.39, 95%CI:-3.02 to -1.77), waist circumference (MD=-4.62, 95%CI:-6.09 to -3.16), fasting blood glucose (MD=-24.59, 95%CI:-28.80 to -20.37), and HbA1c (MD=-0.94, 95%CI: -1.09 to -0.79), while fasting insulin was not significantly changed (MD = 1.21, 95%CI: -0.77 to 3.19). These agents increased likelihood of achieving weight loss, including \u22655% (RR = 2.68, 95% CI: 2.24 to 3.20), \u226510% (RR = 4.14, 95% CI: 3.19 to 5.36), and \u226515% body weight reduction (RR = 10.61, 95% CI: 7.76 to 14.49). Treatment-emergent adverse events (RR = 1.09, 95% CI: 1.06 to 1.12) and overall adverse events (AEs) (RR = 2.75, 95% CI: 2.41 to 3.15) were increased, particularly gastrointestinal events such as nausea, vomiting, diarrhea, constipation, dyspepsia, and abdominal symptoms. However, serious adverse events were not increased (RR = 1.15, 95%CI: 0.93 to 1.43).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Oral small-molecule GLP-1RAs provide significant benefits in weight reduction and glycemic control, supporting their potential role as effective oral incretin therapies. However, their clinical use, should balance these metabolic benefits against high incidence of predominantly gastrointestinal AEs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1854779","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:46:55Z","timestamp":1783403215000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Investigation into the efficacy and safety profile of oral small-molecule GLP-1 receptor agonists in type 2 diabetes and obesity: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Li","family":"Li","sequence":"first","affiliation":[{"name":"Hainan Vocational University of Science and Technology","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianpeng","family":"Shui","sequence":"additional","affiliation":[{"name":"Hainan Vocational University of Science 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