{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:52:06Z","timestamp":1788436326826,"version":"build-2803163510"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"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. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> This meta-analysis aimed to combine the data available from clinical trials to assess the effects of subcutaneous and oral semaglutide administration on glycemic control, weight management, and safety outcomes in patients with type 2 diabetes (T2D).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We systematically searched for phase 3 randomized controlled trials (RCTs) that compared semaglutide with placebo or other anti-diabetic drugs in T2D patients. The primary outcome was the change from baseline in glycated hemoglobin (HbA<jats:sub>1c<\/jats:sub>) levels. Secondary efficacy endpoints included the change from baseline in body weight, achievement of HbA<jats:sub>1c<\/jats:sub> targets, and clinically significant weight loss. Key safety outcomes were also assessed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In this meta-analysis, 24 trials with a total of 22185 patients were included. Subcutaneous semaglutide administration reduced HbA<jats:sub>1c<\/jats:sub> levels (weighted mean difference [WMD]: \u22121.14% and \u22121.37%, for 0.5\u00a0mg and 1\u00a0mg, respectively) and body weight (WMD: \u22122.73\u00a0kg and \u22124.09\u00a0kg, for 0.5\u00a0mg and 1\u00a0mg, respectively) when compared with placebo; its efficacy was also superior to other anti-diabetic drugs in reducing HbA<jats:sub>1c<\/jats:sub> levels (WMD: \u22120.71% and \u22120.86%, for 0.5\u00a0mg and 1\u00a0mg, respectively) and body weight (WMD: \u22122.65\u00a0kg and \u22123.78\u00a0kg, for 0.5\u00a0mg and 1\u00a0mg, respectively). Oral semaglutide administration was superior to placebo in decreasing HbA<jats:sub>1c<\/jats:sub> levels (WMD: \u22120.96% and \u22121.02%, for 7\u00a0mg and 14\u00a0mg, respectively). Moreover, oral administration of 14 mg of semaglutide also showed a significant reduction in HbA<jats:sub>1c<\/jats:sub> levels (WMD: \u22120.36%) compared with other anti-diabetic drugs. Furthermore, oral semaglutide administration resulted in substantial weight loss compared with other anti-diabetic drugs (WMD: \u22121.53\u00a0kg and \u22121.73\u00a0kg, for 7\u00a0mg and 14\u00a0mg, respectively). Notably, subcutaneous and oral semaglutide administration also resulted in higher numbers of patients achieving the targets of HbA<jats:sub>1c<\/jats:sub> levels and weight loss than placebo and other anti-diabetic drugs. Overall, we noted no clear evidence of detrimental effects on safety endpoints due to semaglutide treatment, except for some gastrointestinal adverse events.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Both subcutaneous and oral semaglutide administration could enable the achievement of sufficient glycemic control and weight management without increasing the risk of hypoglycemia, which were effective and safe for the treatment of T2D.<\/jats:p>","DOI":"10.3389\/fphar.2021.695182","type":"journal-article","created":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T21:38:16Z","timestamp":1633556296000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Efficacy and Safety of Subcutaneous and Oral Semaglutide Administration in Patients With Type 2 Diabetes: A Meta-Analysis"],"prefix":"10.3389","volume":"12","author":[{"given":"Ping","family":"Zhong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaochun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"258","DOI":"10.2337\/dc17-0417","article-title":"Efficacy and Safety of Once-Weekly Semaglutide versus Exenatide ER in Subjects with Type 2 Diabetes (SUSTAIN 3): a 56-Week, Open-Label, Randomized Clinical Trial","volume":"41","author":"Ahmann","year":"2018","journal-title":"Diabetes care"},{"key":"B2","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/S2213-8587(17)30092-X","article-title":"Efficacy and Safety of Once-Weekly Semaglutide versus Once-Daily Sitagliptin as an Add-On to Metformin, Thiazolidinediones, or Both, in Patients with Type 2 Diabetes (SUSTAIN 2): a 56-week, Double-Blind, Phase 3a, Randomised Trial","volume":"5","author":"Ahr\u00e9n","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/S2213-8587(17)30085-2","article-title":"Efficacy and Safety of Once-Weekly Semaglutide versus Once-Daily Insulin Glargine as Add-On to Metformin (With or without Sulfonylureas) in Insulin-Naive Patients with Type 2 Diabetes (SUSTAIN 4): a Randomised, Open-Label, Parallel-Group, Multicentre, Multinational, Phase 3a Trial","volume":"5","author":"Aroda","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.2337\/dc19-0749","article-title":"PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison with Placebo in Patients with Type 2 Diabetes","volume":"42","author":"Aroda","year":"2019","journal-title":"Dia Care"},{"key":"B5","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/s2213-8587(17)30412-6","article-title":"Cardiovascular Outcomes with Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes: a Meta-Analysis","volume":"6","author":"Bethel","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.diabet.2019.101117","article-title":"Efficacy and Safety of Once-Weekly Semaglutide 1.0mg vs Once-Daily Liraglutide 1.2mg as Add-On to 1-3 Oral Antidiabetic Drugs in Subjects with Type 2 Diabetes (SUSTAIN 10)","volume":"46","author":"Capehorn","year":"2020","journal-title":"Diabetes Metab."},{"key":"B8","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/jcpt.13230","article-title":"A Review of GLP-1 Receptor Agonists in Type 2 Diabetes: A Focus on the Mechanism of Action of Once-Weekly Agents","author":"Cornell","year":"2020","journal-title":"J. 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