Studies have underscored the favorable impact of coffee intake on maintaining blood glucose levels in humans. In contrast, metformin serves as the standard pharmacological treatment for type 2 diabetes. The present investigation aimed to examine potential roles for coffee either as an adjunct to metformin or as a standalone approach in managing type 2 diabetes. Proteomic information concerning the influence of caffeine and trigonelline—the two principal bioactive components in coffee—on alleviating diabetes was collected and evaluated using protein-protein interaction (PPI) network analysis along with gene ontology enrichment. Whole-blood gene expression data from metformin-responsive diabetic individuals versus healthy controls were retrieved from the GSE83983 dataset in the Gene Expression Omnibus (GEO) repository. After preliminary screening with the GEO2R tool, the markedly differentially expressed genes (DEGs) underwent PPI network analysis and regulatory network examination. Both caffeine and trigonelline actively modulate glycolysis-related pathways to combat diabetes. Metformin substantially impacted several diabetes-associated genes, including HSP90AA1, TLR4, RELA, ARRB, LRRK2, STAT5B, LYN, and TLR2. Findings suggest that regular coffee intake may support blood glucose control in diabetic individuals in ways akin to metformin. Appropriate levels of coffee consumption could potentially function as a regulator of blood sugar in patients with diabetes.
