Lepidine potentiates the antidiabetic effect of metformin in nicotinamide/streptozotocin-induced diabetic male rats

Metformin is used as a first-line treatment of type 2 diabetes mellitus (T2DM) and is effective as monotherapy and in combination with other glucose-lowering medications. Lepidine, a natural product found in <i>Lepidium sativum</i>, had antidiabetic, antioxidant, anticancer, anti-inflammatory, and hypolipidemic effects. This study aimed to assess the effects of lepidine alone and in combination with metformin in nicotinamide (NA)/streptozotocin (STZ)-induced diabetic Wistar rats. T2DM was induced by intraperitoneal injection of NA 15 minutes before intraperitoneal injection of STZ. Diabetic rats were orally treated with lepidine (20 mg/kg body weight) and/or metformin (70 mg/kg body weight) every other day for four weeks. Both lepidine and metformin treated diabetic rats showed a significant decrease in fasting blood glucose (FBG), amelioration of serum lipid profile, increase in serum insulin, and C-peptide , and downregulation in the elevated serum tumour necrosis α (TNF-α) level in association with the improvement in the pancreatic islet integrity and function. In conclusion, the lepidine has potent anti-diabetic effects and may add more to the therapeutic value of metformin when the two agents are used in combination. However, further clinical studies on human beings with T2DM are required to assess the efficacy and safety of the combination of metformin and lepidine before its approval and therapeutic application.