Background Diabetes mellitus is a metabolic disorder characterised by chronic hyperglycemia. The present research work aimed to evaluate the hypoglycaemic, hypolipidemic and antioxidant effects of leafy stems of Cissus polyantha Gilg & Brandt in insulin resistant rats. Methods The oral glucose tolerance test (OGTT) was performed in normal rats. Hyperglycemia was induced for 8 days by a daily subcutaneous injection of dexamethasone (1 mg/kg) one hour after pretreatment of animals with metformin (40 mg/kg) and C. polyantha extract (111, 222 and 444 mg/kg). Body weight, blood glucose, insulin level, lipid profile, insulin biomarkers, cardiovascular indices and oxidative stress biomarkers were evaluated. Results For OGTT, the extract (444 mg/kg) produced a significant drop in blood sugar at the 60th (p < 0.01), 90th (p < 0.01) and 120th min (p < 0.05). Morever, the extract at doses of 222 and 111 mg/kg significantly reduced blood sugar at the 60th (p < 0.01) and 90th min (p < 0.05) respectively. Otherwise, C. polyantha (444 and 222 mg/kg) significantly (p < 0.001) increased body weight and decreased blood sugar on the 4th and 8th days of treatment in insulin resistant rats. The extract also significantly decreased (p < 0.001) serum insulin level, hyperlipidemia, insulin resistance index and cardiovascular indices, and increased gluthathione level, and superoxide dismutase and catalase activity. Conclusion The aqueous extract of Cissus polyantha leafy stems (AECPLS) possess hypoglycemic, hypolipidemic and antioxidant activities that could justify its use in traditional medicine for the prevention and treatment of diabetes mellitus and its complications.

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