What is the benefit of increasing the sulfonylurea dose?

OBJECTIVE

To study the clinical benefit of increasing the dose of the sulfonylurea, glipizide, from 10 to 40 mg per day.

DESIGN

A placebo-controlled, double-blind, cross-over study.

SETTING

An outpatient clinic at the Helsinki University Hospital, Finland.

PATIENTS

Twenty-three patients with noninsulin-dependent diabetes mellitus.

METHODS

Patients were given glipizide in three different dose schedules for 3 months each: 10 mg in the morning or 10 mg or 20 mg in the morning and the evening. Glycemic control was followed by HbA1c measurements and blood glucose monitoring at home. Beta cell function was assessed by measuring insulin responses to a test meal.

RESULTS

Mean home-monitored blood glucose was 12.4 mmol/L during placebo treatment, and it was 9.6, 9.2, and 8.9 mmol/L after treatment with glipizide, 10, 20, or 40 mg, respectively. The levels of blood glucose and HbA1c differed after all treatment groups from placebo (P < 0.001) but not among themselves. The insulin response to a test meal was greatest after 10 mg of glipizide and weakest after 40 mg/d (P = 0.02 compared with the 10-mg dose). All treatments stimulated insulin secretion more than placebo (P < 0.001).

CONCLUSIONS

Increasing the glipizide dose to more than 10 mg once daily produces little or no benefit and may reduce beta-cell function.