ANTI-HYPERGLYCEMIC ACTIVITY OF SIMVASTATIN ALONE (THERAPEUTIC DOSE) AND COMBINATION OF SIMVASTATIN AND GLIPIZIDE (SUB THERAPEUTIC DOSES) ON ALLOXAN INDUCED HYPERGLYCEMIA IN ALBINO RATS

The present study was designed to evaluate anti-hyperglycemic activity of simvastatin alone and the combination of sub therapeutic doses of simvastatin and glipizide. Hyperglycemia was induced experimentally in albino rats by subcutaneous injection of alloxan in a dose of 175 mg/kg body weight. After 72 hours of alloxan treatment, rats showing hyperglycemia (blood glucose level of 400 mg/dl and above) were included in the study. They were divided into four groups of 6 animals each (n=24). Oral administration of normal saline 0.5 ml, glipizide 2.5 mg/kg body weight, simvastatin 10 mg/kg body weight and sub therapeutic doses of both test (simvastatin 5 mg/kg body weight) and standard (glipizide 1.25 mg/kg body weight) drugs, was done respectively into each of the four groups for 30 consecutive days in order to assess the effect in terms of reduction in blood glucose level. Blood glucose was estimated on 0^th, 10^th, 20^th, and 30^th days of study in fixed time intervals. In the test group, there was a gradual fall in the blood glucose level which reached up to 308.3 mg/dl by 30^th day of study (P < 0.001). In case of combination of sub therapeutic doses of simvastatin and glipizide, the fall in blood glucose level was gradual and sustained and it reached up to 201.5 mg/dl by the 30^th day (P < 0.001).  These observations are comparable with the results obtained in case of glipizide treated rats, the standard group. Simvastatin appreciably lowered the blood glucose level, but the combination of sub therapeutic doses of simvastatin and glipizide, by virtue of their possible synergistic effect produced further reduction in the blood glucose level.  This study provides evidence in support of a potential anti-hyperglycemic effect of simvastatin and its combination with glipizide. Thus the combined treatment of simvastatin and glipzide may have added benefit for the diabetic patients associated with hyperlipidemia