Insulin Detemir Is Associated With More Predictable Glycemic Control and Reduced Risk of Hypoglycemia Than NPH Insulin in Patients With Type 1 Diabetes on a Basal-Bolus Regimen With Premeal Insulin Aspart

Abstract

OBJECTIVE -Insulin detemir is a soluble basal insulin analog with a unique mechanism of protracted action designed to reduce the variability associated with conventional basal insulins. This trial compared the glycemic control, risk of hypoglycemia, and effect on body weight of insulin detemir and NPH insulin in patients with type 1 diabetes treated with rapid-acting insulin aspart at meals. RESEARCH DESIGN AND METHODS-This study was a 6-month multinational open parallel-group comparison conducted at 46 centers in five countries and included 448 patients with type 1 diabetes randomized 2:1 to insulin detemir or NPH insulin, respectively. RESULTS -After 6 months, comparable HbA 1c levels were found between the two treatment groups. Fasting plasma glucose tended to be lower in patients treated with insulin detemir, but this difference was not statistically significant (Ϫ0.76 mmol/l, P ϭ 0.097). Within-subject variation in self-measured fasting blood glucose was lower with insulin detemir than with NPH insulin (SD 3.37 vs. 3.78 mmol/l, P Ͻ 0.001). Risk of hypoglycemia was 22% lower with insulin detemir than with NPH insulin (P Ͻ 0.05) and 34% lower for nocturnal (2300 -0600) hypoglycemia (P Ͻ 0.005). Nightly plasma glucose profiles were smoother and more stable with insulin detemir (P ϭ 0.05). Body weight was significantly lower with insulin detemir at the end of the trial (P Ͻ 0.001).CONCLUSIONS -Treatment with insulin detemir resulted in more predictable glycemic control, with smoother plasma glucose profiles than NPH insulin and a significant reduction in the risk of hypoglycemia. The reduction in body weight with insulin detemir is a potential additional advantage. Regimens optimized for insulin detemir may be able to improve glycemic control beyond that possible with NPH insulin.

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

“…In this trial, a significantly lower mean body weight was observed in the insulin detemir/insulin aspart group than in the NPH/regular human insulin group after 18 weeks of treatment. This finding is consistent with findings from other trials with insulin detemir [14,16]. The reason for the difference in weight development is likely to be a difference in food intake, probably due to less defensive snacking in the insulin detemir/insulin aspart group, related to the lower variability in plasma glucose and the reduced risk of hypoglycaemic episodes.…”

“…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]. This profile as well as the improved overall and postprandial glycaemic control obtained in this trial indicates that the combination of insulin detemir and insulin aspart provides near-normal insulin profiles, demonstrating the advantages of these new insulin analogues.…”

“…In earlier trials, lower risk of hypoglycaemia with insulin detemir than with NPH has been observed with comparable HbA 1 c or blood glucose levels [14,15]. This trial has shown that it is indeed possible to lower the risk of hypoglycaemia at the same time as improving glycaemic control.…”

“…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.…”

“…It is an acylated derivative of human insulin [Lys B29 (N ε -tetradecanoyl) des(B30) human insulin], which by a combination of increased self-association and albumin binding contributes to a protracted action, providing a more reproducible absorption and a prolonged action profile [13]. In several multicentre trials in which similar bolus insulin preparations were used for therapy groups, treatment with insulin detemir resulted in predictable glycaemic control with less day-to-day variation and fewer hypoglycaemic episodes than with NPH insulin [14,15,16].…”