Background Ingestion of ethanol before a glucose challenge enhances the insulin response by an unknown mechanism. In addition, epidemiological studies consistently indicate that moderate alcohol consumption reduces the risk of developing type 2 diabetes (T2D). The purposes of this study were to evaluate the potential involvement of glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1) in alcohol-induced augmentation of the insulin response and to determine if red wine acutely improves glucose tolerance during an oral glucose tolerance test (OGTT). Methods Nine subjects (eight T2D and one pre-diabetes) completed two OGTT 30 min after consumption of 263 ml water or red wine (28 g ethanol). Blood samples were obtained for 3 h and analyzed for glucose, insulin, C-peptide, GIP, and GLP-1.Results Compared with water, consumption of red wine increased the incremental area under the curve (iAUC) for insulin by 50 % (14,837 ± 4759 vs. 9885 ± 2686 lU/ ml 9 min; p \ 0.05) and for GIP by 25 % (7729 ± 1548 vs. 6191 ± 1049 pmol/l 9 min; p \ 0.05). Glucose and GLP-1 responses were not affected by red wine. Conclusion Wine consumption before an OGTT augments the insulin response, which may be partially driven by a greater GIP response. Because glucose levels were not reduced, acute wine consumption may not be effective treatment for enhancing glycemic control or may need to be combined with therapy that improves insulin sensitivity.