The effects of long term gliclazide administration on insulin secretion and insulin sensitivity

Gliclazide (80 mg bd) was administered to nine subjects with type 2 (non insulin dependent) diabetes inadequately controlled on diet only. Twenty-four hour glucose, insulin and c-peptide profiles were obtained before and after one week and four months of therapy. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp before and after four months of treatment. Twenty-four hour glucose levels were significantly lowered after one week and four months. Insulin secretion, as assessed by the areas under the insulin and c-peptide curves, was enhanced after one week. The increase was most noted during the day in response to meals. The enhancement was maintained after four months of treatment with the increase in the postabsorptive phase becoming significant. Glucose utilisation rate was significantly increased at four months. It is concluded that both acute and prolonged gliclazide therapy directly or indirectly 1) enhances both meal stimulated and post absorptive insulin secretion and 2) increases insulin sensitivity. The relative contribution of each to improved diabetic control has not been established.