Tabriz University of Medical Sciences Health Promotion Perspectives 2228-6497 16 3 2026 11 05 The Effect of Grape-Seed Extract on Glycemic Control And Insulin Sensitivity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials 328 336 10.34172/hpp.45035 EN Bita Meysami https://orcid.org/0000-0001-9597-5959 Roghayeh Molani-Gol Behzad Alaeddini Vahideh Ebrahimzadeh-Attari https://orcid.org/0000-0002-7017-2129 Journal Article 10.34172/hpp.45035 2025 08 15 2026 05 31 Introduction: Grape seed extract (GSE) supplementation has promising effects on the management of diabetes mellitus. Therefore, the present meta-analysis aimed to assess the effects of GSE on glycemic parameters systematically. Methods: A comprehensive search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for relevant English-language articles published through January 2025. The Cochrane Collaboration’s tool was used to assess the risk of bias in the included studies. Data analysis was performed using STATA 17 with a random-effects model. Heterogeneity among studies was assessed using the I² statistic, and subgroup and sensitivity analyses were conducted. Results: Ten randomized controlled trials (RCTs) were included in the meta-analysis. A significant reduction in insulin levels (WMD=-11.93, 95% CI: -19.94, -3.93; P=0.003) and an increase in the Quicki index (WMD: 0.009, 95% CI: 0.007, 0.012; P=0.000) were observed following GSE supplementation. However, no significant effects were found on fasting blood sugar (FBS), HOMA-IR, HOMA-β, or HbA1c levels (P>0.05). In subgroup analyses, HOMA-IR was reduced in studies with durations<8 weeks and doses<400 mg/day. Conclusion: Improved insulin sensitivity, as reflected by lower insulin levels and an improved Quicki index, may be achieved through GSE intake. These effects could be mediated through inhibition of intestinal α-glucosidase and pancreatic α-amylase activity, increased glucagon-like peptide-1 (GLP-1) release, and insulin-mimetic activity. However, additional large-scale RCTs are required to confirm these findings. Trial registration: The study protocol was registered in the PROSPERO database (CRD42024596397).