Pharmacokinetics, Prandial Glucose Control, and Safety of Insulin Glulisine in Children and Adolescents With Type 1 Diabetes

Abstract

OBJECTIVE -The aim of this study was to investigate the pharmacokinetics, postprandial blood glucose excursions, and safety of insulin glulisine as compared with regular human insulin (RHI), both administered immediately before meals in pediatric patients with type 1 diabetes. RESEARCH DESIGN AND METHODS-A total of 10 children (aged 5-11 years) and 10 adolescents (aged 12-17 years) were enrolled in a randomized, single-center, single-dose, double-blind, cross-over study. The blood glucose of fasting patients was stabilized with intravenous insulin, following which patients received 0.15 IU/kg of subcutaneously injected insulin glulisine or RHI 2 min before a weight-adjusted standardized liquid meal.RESULTS -For insulin glulisine versus RHI, maximum insulin concentrations (58 vs. 33 IU/ml, P Ͻ 0.05) and initial insulin concentrations (insulin [area under the curve] AUC 0 -2h 5,232 vs. 2,994 IU ⅐ min Ϫ1 ⅐ ml Ϫ1 , P Ͻ 0.05; data are geometric means) were higher after insulin glulisine than RHI. Both time to maximum insulin concentration (54 vs. 66 min) and mean residence time (88 vs. 137 min, P Ͻ 0.05) were shorter with insulin glulisine versus RHI. Postprandial glucose excursions after insulin glulisine were lower than after RHI (glucose AUC 0 -6h 641 vs. 801 mg ⅐ h Ϫ1 ⅐ dl Ϫ1 , P Ͻ 0.05). The pharmacokinetic profile for insulin glulisine was similar for children and adolescents, whereas the pharmacokinetic profile for RHI demonstrated a 64% higher concentration in adolescents. Insulin glulisine was safe and well tolerated.CONCLUSIONS -The rapid-acting properties of insulin glulisine that have been previously demonstrated in adults are also observed in children and adolescents with type 1 diabetes. Further, these initial data indicate that insulin glulisine is safe and well tolerated in this patient population. Diabetes Care 28:2100 -2105, 2005T he goal of basal-bolus insulin therapy in type 1 diabetes is to achieve near to normal glycemic control and reduce the risk of long-term clinical complications (1). Children and adolescents sometimes encounter difficulties in adjusting their daily activities to fixed intervals between insulin administration and meals, particularly with regular human insulin (RHI), which requires administration 30 -45 min before mealtime (2). The use of rapid-acting insulin analogs instead of RHI for prandial glycemic control is becoming increasingly accepted, since these insulins can be given much closer to mealtime (2-4). Thus, rapid-acting insulin analogs might offer advantages, particularly for very young children in whom the actual carbohydrate intake is often difficult to predict (5). It remains to be shown, however, whether the rapidacting properties of these analogs are preserved in children.Insulin glulisine ([LysB3, GluB29]-insulin) is a recombinant insulin analog designed to provide the same total glucodynamic effect as RHI after subcutaneous administration but with a faster onset and shorter duration of action (6), which has been demonstrated in adults (7-9). The altered absorpt...

Comparable Efficacy and Safety of Insulin Glulisine and Insulin Lispro When Given as Part of a Basal–Bolus Insulin Regimen in a 26-Week Trial in Pediatric Patients with Type 1 Diabetes

“…This trial extends the findings of a previous study comparing glulisine with RHI in children and adolescents with type 1 diabetes, 25 which confirmed that the rapid onset of glulisine observed in adults 6,[26][27][28] is also seen in the pediatric population. Pharmacokinetic studies comparing glulisine and lispro in lean-to-obese subjects without diabetes showed comparable glucodynamic efficacy between both insulins.…”

Efficacious and safe control of glycemia using Apidra insulin

“…Эффективность и безопасность инсулина глулизин у пациен-тов с СД подтверждена результатами многих клинических иссле-дований [21,22,28]. Два больших исследования III фазы у больных СД1 были посвящены изучению эффективности глу-лизина как компонента базально-болюсного режима в комбина-ции с назначением один раз в сутки беспикового аналога длительного действия инсулина гларгин [21,29].…”

“…В недавнем исследовании 18 пациентов с ожи-рением (ИМТ от 30 до 40 кг/м 2 ) без нарушения углеводного об-мена получали подкожные инъекции глулизина, лизпро и ЧИКД по заранее разработанной схеме [24]. Результаты этого исследования выявили ускоренное начало утилизации глюкозы под действием глулизина и лизпро по сравнению с ЧИКД, при этом инсулин глулизин показал даже более раннее начало ути-лизации и более быстрое время достижения 20% общей утили-зации глюкозы, чем лизпро [28] (рис. 4).…”

“…При оценке фармакокинетики и глюкодинамического действия глулизина у 10 детей 5-11 лет и 10 подростков 12-17 лет с СД1, которым вводили подкожно глулизин или ЧИКД за две минуты до стандартного пищевого теста, выявлено, что максимальная концентрация в крови и начальное воздействие (в течение 1 и 2 часов после начала еды) у глулизина были выше, а среднее резидентное время короче [28]. Постпрандиальные колебания гликемии были меньше у глулизина, чем у ЧИКД, при этом со-держание глюкозы имело тенденцию к снижению в конце 6-ча-сового периода мониторинга.…”

Potential Advantages of a Basal–Bolus Regimen Using Insulin Glulisine as Prandial Insulin

“…8 The short-acting profile of insulin glulisine is also maintained across different ethnic groups, paediatric patients and subjects with altered renal function. [9][10][11] The potential advantages of insulin glulisine in obese subjects deserve a separate commentary. It is well known that increased SC thickness alters insulin absorption, shifting the time-action profile curves to the right.…”