Use of insulin aspart, a fast-acting insulin analog, as the mealtime insulin in the management of patients with type 1 diabetes.

Abstract

OBJECTIVE: To compare long-term glycemic control and safety of using insulin aspart (IAsp) with that of regular human insulin (HI). RESEARCH DESIGN AND METHODS: This was a multicenter randomized open-label 6-month study (882 subjects) with a 6-month extension period (714 subjects) that enrolled subjects with type 1 diabetes. Subjects administered IAsp immediately before meals or regular HI 30 min before meals; basal NPH insulin was taken as a single bedtime dose in the majority of subjects. Glycemic control was assessed with HbA1c values and 8-point blood glucose profiles at 3-month intervals. RESULTS: Mean postprandial blood glucose levels (mg/dl +/- SEM) were significantly lower for subjects in the IAsp group compared with subjects in the HI group after breakfast (156 +/- 3.4 vs. 185 +/- 4.7), lunch (137 +/- 3.1 vs. 162 +/- 4.1), and dinner (153 +/- 3.1 vs. 168 +/- 4.1), when assessed after 6 months of treatment. Mean HbA1c values (% +/- SEM) were slightly, but significantly, lower for the IAsp group (7.78% +/- 0.03) than for the regular HI group (7.93% +/- 0.05, P = 0.005) at 6 months. Similar postprandial blood glucose and HbA1c values were observed at 12 months. Adverse events and overall hypoglycemic episodes were similar for both treatment groups. CONCLUSIONS: Postprandial glycemic control was significantly better with IAsp compared with HI after 6 and 12 months of treatment. The improvement was not obtained at an increased risk of hypoglycemia. HbA1c was slightly, but significantly, lower for IAsp compared with HI at 6 and 12 months.

Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal-bolus therapy for patients with Type 1 diabetes

“…Rapid-acting insulin analogues contribute less to the basal insulin profile, as they have a shorter duration of action than regular human insulin, and therefore the basal insulin dose must often be increased to compensate. This has been demonstrated in large-scale studies [9,10]. Excessive weight gain has been identified as a major concern with long-term intensive therapy of Type 1 diabetes mellitus [26].…”

“…For this reason, the combination of insulin detemir and insulin aspart, both exhibiting more physiological insulin profiles than NPH and regular human insulin [11,13], was chosen to compare with the traditional basalbolus regimen. Furthermore, both insulin aspart and insulin detemir have demonstrated certain clinical improvements over regular human insulin and NPH insulin respectively [9,10,11,12,14,15,16]. Therefore, it was hypothesised that the combination of these two insulin analogues in basal-bolus therapy would realise the potential of each, and demonstrate significant clinical advantages over an NPH and regular human insulin regimen.…”

“…Recent basal-bolus trials with rapid-acting insulin analogues and NPH have shown significant improvements in postprandial glucose control [9,10,20], but these improvements only translated into small improvements in HbA 1 c. This suggested that optimisation of the basal insulin supply by the use of basal insulin analogues could lead to further improvements in glycaemic control [21,22]. In the current trial and earlier studies, insulin detemir has been shown to have a smooth time-action profile, meeting patients' basal insulin requirements [13,14].…”

“…First, rapid-acting insulin analogues such as insulin aspart were developed to mimic the normal mealtime insulin response more closely than injection of regular human insulin, and thereby to improve postprandial glycaemic control. This advantage, together with a reduced risk of hypoglycaemic episodes, has been demonstrated in several studies [9,10,11,12]. However, the short duration of action of these analogues means that they contribute little to the between-meal basal insulin level, so patients are often obliged to increase the dose of their basal preparation.…”

Insulin therapy—realising the potential

“…First to be produced were the rapid-acting insulin analogues, insulin aspart and insulin lispro, that had more rapid absorption and shorter duration of action than shortacting human insulin and thus made them ideal candidates for the control of postprandial glucose levels. [1][2][3][4][5] Further manipulations of the protein structure of insulin have created, in the last few years, the first basal insulin analogues, more suited to providing the constant, smooth basal insulin requirements than conventional long-and intermediate-acting human insulin preparations. 6 The improved pharmacokinetics of these analogue insulins now allow us to aim for fasting and postprandial glycaemic targets which were previously out of reach for many patients.…”