Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance. Gegen Qinlian decoction (GQD), a traditional Chinese medicine (TCM) formula, has shown hypoglycemic effects, but its use in functional food is limited by potential side effects from certain components. This study developed a food-medicine homologous alternative formula, Gesang Pipa decoction (GPD), by substituting Coptidis Rhizoma and Scutellariae Radix with Eriobotrya japonica leaves and Mori Folium , respectively. GPD maintained a 92.9% target overlap with GQD. In db/db mice, GPD significantly reduced fasting blood glucose (FBG) by 40.2%, comparable to metformin (37.7%) and GQD (39.2%). Oral glucose tolerance tests (OGTT) confirmed its efficacy in improving glucose homeostasis. Additionally, GPD modulated lipid metabolism, reduced triglycerides, and improved liver function. Multi-omics analysis revealed that GPD and GQD share similar metabolic pathways, including glycerophospholipid metabolism, while GPD's flavonoid-enriched composition plays a crucial role in insulin sensitization. These findings suggest that GPD is a promising, safer alternative to GQD for long-term T2DM management.