{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:32:45Z","timestamp":1792006365142,"version":"4.4.0"},"reference-count":44,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RCSI Bahrain"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Type 2 diabetes mellitus (T2DM) is characterized by progressive \u03b2-cell dysfunction and insulin resistance. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may enhance \u03b2-cell function. Semaglutide, a long-acting GLP-1 RA, improves glycemic control and weight, but its direct effects on \u03b2-cell function remain uncertain. Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251034071). PubMed, Embase, and Scopus were searched through April 2025 for randomized controlled trials evaluating semaglutide\u2019s effects on \u03b2-cell function in adults with T2DM. Primary outcomes included HOMA-B, HOMA-IR, and the proinsulin\/insulin ratio; secondary outcomes included insulin secretion rate, insulinogenic index, and C-peptide. Two reviewers independently performed data extraction and risk-of-bias assessment using the Cochrane RoB 1 tool. Random-effects models were used for pooling. Certainty of evidence was evaluated using GRADE. Results: Sixteen trials (n = 6591) met inclusion criteria, with nine included in the meta-analysis. Semaglutide improved \u03b2-cell function (HOMA-B log ratio of means 1.50, 95% confidence interval [CI]: 1.25\u20131.80) and reduced insulin resistance (HOMA-IR ratio 0.82, 95% CI: 0.73\u20130.94) compared with placebo or active comparators. The pooled treatment ratio for proinsulin\/insulin was 0.70 (95% CI: 0.63\u20130.79). However, risk of bias was generally high due to open-label designs, and certainty of evidence for all primary outcomes was rated very low. Conclusions: Semaglutide appears to improve \u03b2-cell function and insulin sensitivity in adults with T2DM, but conclusions remain uncertain given the very low certainty of evidence and substantial heterogeneity. High-quality trials with standardized \u03b2-cell outcomes are needed to confirm these findings.<\/jats:p>","DOI":"10.3390\/jcm14248734","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T16:11:18Z","timestamp":1765383078000},"page":"8734","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Effect of Semaglutide on Pancreatic \u03b2-Cell Function in Adults with Type 2 Diabetes: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5072-5372","authenticated-orcid":false,"given":"Omar","family":"Abusedera","sequence":"first","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland-Bahrain, Busaiteen 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6921-8390","authenticated-orcid":false,"given":"Jana","family":"Sherif","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland-Bahrain, Busaiteen 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6988-5315","authenticated-orcid":false,"given":"Malak","family":"Smida","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland-Bahrain, Busaiteen 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Fredericks","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland-Bahrain, Busaiteen 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K.B., Ostolaza, H., and Mart\u00edn, C. 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