to compare the glycemic response to an insulin lispro mixture (25% insulin lispro and 75% NPL) twice daily plus metformin (Mix25+M) with glibenclamide plus metformin (G+M), in patients with type 2 diabetes inadequately controlled with a single oral agent.597 patients treated in a randomized, open-label, 16-week parallel study. Variables evaluated: hemoglobin A1C (A1C), patient symptoms, hypoglycemia rate (episodes/patient/30 days), and incidence (% patients experiencingor =1 episode). For a subset of patients (N=120), fasting, 1-h, and 2-h postprandial plasma glucose (FPG, 1-h ppPG, 2-h ppPG) in response to a standardized test meal (STM) and self-monitored blood glucose (BG) profiles were measured.improved A1C at endpoint for both groups, and A1C changes from baseline to endpoint were not significantly different between treatments (Mix25+M, -1.87+/-1.35% vs. G+M, -1.98+/-1.28%; p=0.288). Among patients completing STM; endpoint 2-h ppPG was significantly lower with Mix25+M (9.05+/-3.32 mmol/l vs. 12.31+/-3.65 mmol/l; p0.001), as was 2-h ppPG excursion (2-h ppPGex)(0.38+/-3.23 mmol/l vs. 2.88+/-1.98 mmol/l; p0.001). Percentage of patients achieving postprandial BG targets (10 mmol/l) at endpoint was significantly greater with Mix25+M (80% vs. 48%; p0.001). Although, overall hypoglycemia rates were similar, percentage of patients experiencing and rate of nocturnal hypoglycemia was less with Mix25+M (1% vs. 5%; p0.01, and 0.01 vs. 0.08 episodes/pt/30 d; p=0.007). Patients reported less polyuria with Mix25+M (p0.001).in patients with type 2 diabetes failing on metformin or a sulfonylurea, Mix25+M provided similar overall glycemic control, lower ppPG, reduced nocturnal hypoglycemia, and fewer hyperglycemic symptoms compared to G+M.