Adding a second antihyperglycemic agent, regardless of its timing of action, lowers HbA1c and glucose values. However, when insulin lispro was used to focus on postprandial blood glucose, there was a greater impact on overall metabolic control. These data support the importance of lowering postprandial blood glucose to optimize overall glycemic control and thus improve long-term outcomes.

The structure of the hormone glucagon is identical among humans and several species of other mammals. Equivalence of recombinant glucagon (rG) to animal-source glucagon (aG) was assessed in this two-part, open-label, randomized study. Part I was a four-way crossover intravenous dose-ranging study of rG (pH 2.8) involving 12 subjects. Part II was a six-way crossover study of 29 subjects comparing rG (diluent pH 2.0 and 2.8) with aG administered subcutaneously (sc) and intramuscularly (im). Maximum glucagon plasma concentrations (C(max)) and area under the glucagon concentration curve (AUC) were calculated. Additionally, maximum blood glucose concentrations (BG(max)), maximum absolute BG excursion (MAE), and area under the glucose concentration curve from time of dosing to return to baseline (AUC(rtb)) were calculated. The primary focus was equivalence of the formulation intended for marketing (rG pH 2.0) to aG. Administration of rG pH 2.0 through the im route demonstrated equivalence to aG for all pharmacokinetic and glucodynamic comparisons. Subcutaneous administration of rG pH 2.0 demonstrated standard bioequivalence for AUC (5.87 versus 6.63 ng x h/mL; NS) and near equivalence for C(max) (7.94 versus 9.12 ng/mL; p < 0.05). rG pH 2.0 showed glucodynamic equivalence to aG (BG(max), 136 versus 133 mg/dL; MAE, 50.0 versus 47.4 mg/dL, respectively) and statistically greater AUC(rtb) values (151 versus 126 mg x h/dL, p < 0. 05). rG and aG were equally safe and well tolerated. In conclusion, rG provides equivalent safety and efficacy to aG.

Insulin lispro when diluted with the appropriate diluent demonstrates acceptable stability when stored at 5 degrees C and 30 degrees C for a period of 32 days.