GLIMEPIRIDE, A NEW ONCE-DAILY SULFONYLUREA - A DOUBLE-BLIND PLACEBO-CONTROLLED STUDY OF NIDDM PATIENTS

OBJECTIVE - To compare the efficacy and safety of two daily doses of t he new sulfonylurea, glimepiride (Amaryl), each as a once-daily dose o r in two divided doses, in patients with NIDDM. RESEARCH DESIGN AND ME THODS - Of the previously treated NIDDM patients, 416 entered this mul ticenter randomized double-blind placebo-controlled fixed-dose study. After a 3-week placebo washout, patients received a 14-week course of placebo or glimepiride 8 mg q.d., 4 mg b.i.d., 16 mg q.d., or 8 mg b.i .d. RESULTS - Fasting plasma glucose (FPG) and HbA(1c) values were sim ilar at baseline in all treatment groups. The placebo group's FPG valu e increased from 13.0 mmol/l at baseline to 14.5 mmol/l at the last ev aluation endpoint (P less than or equal to 0.001). In contrast, FPG va lues in the four glimepiride groups decreased from a range of 12.4-12. 9 mmol/l at baseline to a range of 8.6-9.8 mmol/l at endpoint (P less than or equal to 0.001, within-group change from baseline; P less than or equal to 0.001, between-group change [vs. placebo] from baseline). Two-hour postprandial plasma glucose (PPG) findings were consistent w ith FPG findings. In the placebo group, the HbA(1c) value increased fr om 7.7% at baseline to 9.7% at endpoint (P less than or equal to 0.001 ), whereas HbA(1c) values for the glimepiride groups were 7.9-8.1% at baseline and 7.4-7.6% at endpoint (P less than or equal to 0.001, with in group change from baseline; P less than or equal to 0.001,between-g roup change from baseline). There were no meaningful differences in gl ycemic variables between daily doses of 8 and 16 mg or between once- a nd twice-daily dosing. Adverse events and laboratory data demonstrate that glimepiride has a favorable safety profile. CONCLUSIONS - Glimepi ride is an effective and well-tolerated oral glucose-lowering agent. T he results of this study demonstrate maximum effectiveness can be achi eved with 8 mg q.d. of glimepiride in NIDDM subjects.