Abstract
Introduction: Grape seed extract (GSE) supplementation has promising effects on the management of diabetes mellitus. Therefore, the present meta-analysis aimed to systematically assess the effects of GSE on glycemic parameters. Method: 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. Result: 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)