{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:27:48Z","timestamp":1786116468664,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is approved for weight management as both a weekly subcutaneous (s.c.) injection (2.4 mg) and a daily oral tablet (50 mg). Although head-to-head trials are lacking, the oral formulation offers potential advantages in adherence, patient preference, and accessibility. This systematic review critically appraised comparative and formulation-specific evidence to characterise the efficacy, safety, pharmacokinetics, and patient-reported outcomes of oral vs. s.c. semaglutide in adults with obesity or overweight with at least one weight-related comorbidity. Methods: PubMed, Google Scholar, and SciSpace were searched from inception to June 2025, applying PRISMA 2020 guidelines. Eligibility criteria (PICO): adults with BMI \u2265 27 kg\/m2; intervention, oral semaglutide (any dose); comparator, s.c. semaglutide or placebo; outcomes, body weight, BMI, cardiometabolic markers, adverse events, adherence. Risk of bias was assessed with RoB 2.0 (RCTs) and AMSTAR-2 (systematic reviews). Results: Thirty studies met inclusion criteria (12 RCTs, nine systematic reviews\/meta-analyses, five comparative\/observational studies, four pharmacokinetic studies). OASIS 1 demonstrated \u221215.1% body weight reduction with oral semaglutide 50 mg at 68 weeks, comparable to s.c. semaglutide 2.4 mg (\u221214.9% in STEP 1). Both formulations significantly improved HbA1c, blood pressure, and lipid profiles. Oral bioavailability (~1%) requires co-administration with the SNAC absorption enhancer; s.c. bioavailability is ~89%. Oral semaglutide showed superior patient preference and equivalent adherence in needle-averse patients. Conclusions: Oral semaglutide 50 mg is a clinically valid alternative to s.c. semaglutide for obesity management, offering equivalent efficacy and an improved patient experience for individuals who prefer needle-free treatment. Robust direct comparative trials are needed.<\/jats:p>","DOI":"10.3390\/ph19081236","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:46:38Z","timestamp":1786009598000},"page":"1236","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral vs. Subcutaneous Semaglutide for Obesity Treatment: A Systematic Review of Efficacy, Safety, and Patient-Oriented Outcomes"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-2372","authenticated-orcid":false,"given":"Sandro","family":"La Vignera","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5217-9343","authenticated-orcid":false,"given":"Rosita A.","family":"Condorelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","unstructured":"WHO (2025, June 01). 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