Effect of metformin treatment on glucose tolerance and glomerulosclerosis in KK mice

Non-obese KK mice, aged 90-100 days, demonstrating an abnormal tolerance to glucose, hyperinsulinaemia with insulin resistance and glomerulosclerosis were treated with either water (control N = 10) or metformin (N = 15), a biguanide, orally at a concentration of 50 mg/kg twice daily for 16 weeks. Oral glucose tolerance was performed at 7 weeks. Only 10 of 15 metformin-treated mice (responders) improved their oral glucose tolerance. The remaining 5 mice (non-responders) did not improve their tolerance to the oral glucose load. A repeated oral glucose tolerance test at 16 weeks showed similar results. Blood lactate and insulin levels were similar in all 3 groups of mice. At sacrifice, responders had significantly less glomerulosclerosis compared to control mice. No difference in the incidence of glomerulosclerosis was found between control mice and non-responders. The data suggest that chronic metformin treatment improves glucose tolerance in 70% of KK mice without increasing blood lactate or insulin levels. This improvement in glycaemic control is associated with a lesser incidence of glomerulosclerosis in KK mice.