SHORT-TERM COMPARISON OF ONCE-DAILY VERSUS TWICE-DAILY ADMINISTRATIONOF GLIMEPIRIDE IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS

OBJECTIVE: To investigate the metabolic effects and frequency of adver se events with 6 mg of glimepiride, a new oral sulfonylurea, given bot h in once- and twice-daily dosages to patients with noninsulin-depende nt diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: This 15-wee k study involved 161 subjects with NIDDM. Subjects were randomized int o two groups. For 4 weeks, group 1 received glimepiride 3 mg twice dai ly, and group 2 received glimepiride 6 mg once daily. After a 3-week p lacebo-washout period, twice- and once-daily regimens were crossed ove r for a second 4-week treatment period. Subjects were hospitalized at the end of each placebo or active-treatment phase. Their glucose conce ntrations were recorded at 20 time points over a 24-hour period, and t heir insulin and C-peptide concentrations were recorded at 16 time poi nts over the same period. Parameters that were calculated included fas ting, 24-hour, and postprandial concentrations of glucose, insulin, an d C-peptide. RESULTS: One hundred six patients were randomized to rece ive treatment; 94 completed the entire study. Existing physiologic mec hanisms of glucose control were apparently unimpaired by glimepiride t reatment. Insulin concentrations increased more during the postprandia l glucose peaks than when subjects were fasting. Both twice- and once- daily regimens proved equally effective in reducing concentrations of fasting, postbreakfast, postlunch, and postdinner plasma glucose. Twen ty-four-hour mean glucose concentrations showed a slightly greater dec rease from baseline for the twice-daily regimen; the difference betwee n the regimens was statistically significant but not clinically meanin gful. The incidence of adverse events with glimepiride approximated th at obtained with placebo, with both groups reporting only one adverse event, headache, in more than 5% of the subjects. CONCLUSIONS: Glimepi ride is equally effective whether administered once or twice daily. Gl imepiride seems to stimulate insulin production primarily after meals, when plasma glucose concentrations are highest, but controls blood gl ucose throughout the day.