Comparative efficacy of preprandial or postprandial Humalog® Mix75/25™ versus glyburide in patients 60 to 80 years of age with type 2 diabetes mellitus

Background: Humalog(R) Mix75/25(TM) (Mix75/25) is a novel premixed insulin containing 75% neutral protamine lispro (an intermediate-acting insulin) and 25% insulin lispro. Objective: The purpose of this study was to compare glycemic control and hypoglycemia rates with Mix75/25 versus glyburide, and with preprandial versus postprandial Mix75/25, in patients aged 60 to 80 years with type 2 diabetes mellitus and persistent hyperglycemia on sulfonylurea therapy. Methods: In this open-label, 16-week, parallel-group study, patients were randomized to I of 2 treatments: glyburide 15 mg/d (or up to the maximum daily dose) or Mix75/25. The Mix75/25 group was randomly subdivided into preprandial (immediately before breakfast and dinner) and postprandial (within 15 minutes after the start of breakfast and dinner) injection subgroups. The primary outcomes were glycemic control and rate of hypoglycemia. Results: A total of 143 patients were randomized; 127 completed the study. The change in glycosylated hemoglobin (HbA(1c)) from baseline to end point was significantly greater with Mix75/25 than with glyburide (mean +/- SEM, -1.14% +/- 0.18% vs -0.36% +/- 0.15%, P = 0.001). HbA(1c) changes with preprandial and postprandial Mix75/25 were not significantly different (-1.20% +/- 0.26% vs -1.08% +/- 0.26%, P = 0.748). Fasting blood glucose (BG), 2-hour postprandial BG, and mean daily BG reductions were greater with Mix75/25 than with glyburide (P < 0.001); preprandial and postprandial Mix75/25 administration did not differ significantly with respect to any of these BG variables. The hypoglycemia rate increased with Mix75/25 by 0.17 +/- 0.02 episodes per patient per 30 days, but there was no change with glyburide (P = 0.077). Body weight increased by 1.02 +/- 0.35 kg with Mix75/25 and decreased by 0.85 +/- 0.18 kg with glyburide (P < 0.001). Conclusions: Compared with glyburide, Mix75/25 significantly improved glycemic control in older patients with type 2 diabetes mellitus, could be administered after meals without compromising glycemic control, and was well tolerated.