LONG-TERM EFFECTS OF GLIPIZIDE ON INSULIN-SECRETION AND BLOOD-GLUCOSE CONTROL IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Of 23 patients with non-insulin-dependent diabetes mellitus (NIDDM), whose fasting blood glucose had not reached less-than-or-equal-to 6.0 mmol.l-1 after 10 weeks of dietary regulation, 15, who had had a weight reduction of -2.8 kg by dietary control, did achieve a fasting blood glucose less-than-or-equal-to 6.0 mmol.l-1 after addition of less-than-or-equal-to 20 mg glipizide daily. They had a sustained (greater-than-or-equal-to 2 years) increase in meal-induced insulin secretion (32% increase in postprandial C-peptide AUC), and a sustained reduction in postprandial hyperglycaemia (34% reduction in AUC). Ten of the patients took a mean daily dose < 5 mg (4.8 mg) and had a sustained increase in insulin secretion rate (increased C-peptide slope). The 15 patients had no elevation of basal insulin secretion and no impairment of weight reduction. The remaining 8 subjects, who showed little or no weight reduction on dietary control, had little or no reduction in fasting blood glucose despite long-term treatment with 20 mg glipizide daily, a less sustained increase in meal-induced insulin secretion, a smaller reduction of postprandial hyperglycaemia, and an increase in body weight. On diagnosis the 8 subjects did not differ from the other 15 subjects in age, body weight, blood glucose, HbA1c, C-peptide or insulin, nor in their glucose and insulin responses to a test dose of glipizide; the main reason for the apparent drug failure appeared to be deficient compliance with dietary regulation rather than a primary inability to respond to sulphonylurea treatment. The findings indicate that glipizide is able to promote and maintain increased meal-induced insulin secretion and near-normal fasting and non-fasting blood glucose levels without continuous B cell stimulation. However, these improvements prevail mainly in subjects who persist with hypocaloric dietary regulation.