Background/Objectives: Type 2 diabetes mellitus (T2DM) is characterized by progressive β-cell dysfunction and insulin resistance. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may enhance β-cell function. Semaglutide, a long-acting GLP-1 RA, improves glycemic control and weight, but its direct effects on β-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’s effects on β-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 β-cell function (HOMA-B log ratio of means 1.50, 95% confidence interval [CI]: 1.25–1.80) and reduced insulin resistance (HOMA-IR ratio 0.82, 95% CI: 0.73–0.94) compared with placebo or active comparators. The pooled treatment ratio for proinsulin/insulin was 0.70 (95% CI: 0.63–0.79). 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 β-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 β-cell outcomes are needed to confirm these findings.

Background:Polycystic Ovary Syndrome (PCOS) is commonly managed with metformin, a drug known to influence vitamin B12 and homocysteine levels. While these biochemical alterations are well-documented in diabetic populations, limited data exists on their relevance in PCOS patients. Objective:This systematic review and meta-analysis aimed to evaluate the impact of metformin on vitamin B12 and homocysteine levels in women diagnosed with PCOS. Methods:We systematically searched PubMed and other major databases for studies published between 2015 and 2025. Eligible studies included randomized controlled trials and observational studies comparing pre- and post-metformin levels of vitamin B12 and homocysteine in PCOS patients. Independent reviewers screened articles, extracted data, and assessed study quality. A random-effects meta-analysis was conducted to generate pooled effect estimates. Results:The analysis revealed no consistent effect of metformin on homocysteine levels, with moderate heterogeneity across studies (I² = 36%). Variations in study design, treatment duration, metformin dosage, and measurement techniques contributed to this heterogeneity. The impact on vitamin B12 levels was variably reported and could not be conclusively synthesized due to data limitations. Conclusion:Metformin’s effect on homocysteine levels in PCOS appears inconsistent and influenced by multiple factors. Further high-quality, standardized studies are needed to clarify its role in altering vitamin B12 and homocysteine profiles in this population.