[Lys(B28), Pro(B29)]-human insulin: Effect of injection time on postprandial glycemia

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Abstract
Background: [Lys(B28), Pro(B29)]-human insulin (lispro) is an insulin analogue with a reduced capacity for self-association and faster absorption from subcutaneous injection sites. We hypothesized that administration of lispro closer to a meal would result in better glucose control than that achieved with regular insulin. Methods: This trial used a randomized crossover design that consisted of a period of metabolic stabilization lasting 9 days followed by an evaluation period lasting 5 days. The patients received weight-maintenance diets, and insulin doses were adjusted as needed, Calorie intake, insulin dose, and activities were kept constant once the evaluation period began. During the evaluation period, we varied the time between insulin injection and mealtime and assessed glucose control. Results: During the evaluation period, the lowest mean glucose concentrations were 117.9 mg/dl for lispro and 119.8 mg/dl (p = 0.817) for regular insulin. To obtain these, we gave lispro, on average, 22.5 minutes before meals and regular insulin 63.8 minutes before meals (p = 0.006). A similar pattern was evident throughout the glucose control parameters. The exception was mean amplitude of glucose excursion, which was lower after lispro (59 versus 75 mg/dl; p = 0.007) compared with regular insulin. Conclusions: We achieved equal or slightly better glucose control, as reflected by mean amplitude of glucose excursion, with insulin lispro given much closer to meal time than that achieved with regular insulin. As a result of these findings, we propose that a rapidly absorbed analogue of insulin is capable of achieving better control of postprandial glucose at a more convenient injection time.