Anti-diabetic effects of compound K versus metformin versus compound K-metformin combination therapy in diabetic db/db mice

Compound K (CK) is a major intestinal metabolite of ginsenosides derived from ginseng radix. In our preliminary studies, CK has shown to exhibit anti-hyperglycemic effect through its insulin-secreting action, similar to that of insulin secretagogue sulfonylureas. Metformin, a biguanide, improves insulin resistance by reducing gluconeogenesis and enhancing peripheral glucose uptake, promoting reduction of the plasma glucose level. The aim of this study was to compare the anti-diabetic effects of CK and metformin due to differences in their mechanisms of action and also to investigate whether treatment of CK and metformin in combination show synergistic or additive effects compared to each drug alone. Seven week-old male db/db mice were treated for 8 weeks. CK was given at a dose of 10 mg/kg, metformin at 150 mg/kg and the same dosage of each drug was applied to CK plus metformin combination group. Significant improvements were observed in plasma glucose and insulin levels, homeostasis model assessment-insulin resistance (HOMA-IR) index and in hematoxylin and eosin-stained liver tissues in combination group. Although further studies to elucidate the benefits of co-administration of CK and metformin are needed, our findings may provide basis to the discovery of a new combination therapy on diabetes control in type 2 diabetics.