OBJECTIVE To assess the efficacy, safety, and dose-response relationship of glimepiride in patients with NIDDM.

RESEARCH DESIGN AND METHODS After a 21-day placebo washout period, 304 patients were randomized to receive either placebo or glimepiride, 1, 4, or 8 mg once daily. Fasting plasma glucose (FPG), 2-h postprandial glucose (PPG), and HbA_1c were measured at predetermined intervals during the washout period and the 14-week study. Adverse events were tabulated.

RESULTS At each patient visit, reduction from baseline FPG was greater in each glimepiride group than in the placebo group (P < 0.001). Changes from baseline to endpoint after 1, 4, and 8 mg glimepiride exceeded those after placebo (P < 0.001) by 2.4, 3.9, and 4.1 mmol/l, respectively, for FPG; by 1.2, 1.8, and 1.9 percentage points, respectively, for HbA_1c; and by 3.5, 5.1, and 5.2 mmol/l, respectively, for 2-h PPG. Greater reductions in these parameters were observed with 8 and 4 mg than with 1 mg (P < 0.05), indicating a dose-response relationship. When patients with baseline HbA_1c levels ≥ 8% were assessed, more patients who received 8 mg glimepiride had HbA_1c values < 8% at endpoint compared with patients receiving 4 mg. Glimepiride had a favorable safety profile.

CONCLUSIONS Glimepiride in 1-, 4-, or 8-mg doses was effective and well tolerated. Although the 4- and 8-mg once-daily doses were significantly more potent than the 1-mg dose, all three doses yielded clinical improvement. Because the 8-mg dose controlled HbA_1c values in a greater number of patients with high baseline HbA_1c levels than did the 4-mg dose, this higher dose might be beneficial for patients who are difficult to treat.