Insulin Detemir Offers Improved Glycemic Control Compared With NPH Insulin in People With Type 1 Diabetes

Abstract

OBJECTIVE -Insulin detemir is a soluble long-acting basal insulin analog designed to overcome the limitations of conventional basal insulin formulations. Accordingly, insulin detemir has been compared with NPH insulin with respect to glycemic control (HbA 1c , prebreakfast glucose levels and variability, and hypoglycemia) and timing of administration.RESEARCH DESIGN AND METHODS -People with type 1 diabetes (n ϭ 408) were randomized in an open-label, parallel-group trial of 16-week treatment duration using either insulin detemir or NPH insulin. Insulin detemir was administered twice daily using two different regimens, either before breakfast and at bedtime (IDet mornϩbed ) or at a 12-h interval (IDet 12h ). NPH insulin was administered before breakfast and at bedtime. Mealtime insulin was given as the rapid-acting insulin analog insulin aspart.RESULTS -With both insulin detemir groups, clinic fasting plasma glucose was lower than with NPH insulin (IDet 12h vs. NPH, Ϫ1.5 mmol/l [95% CI Ϫ2.51 to Ϫ0.48], P ϭ 0.004; IDet mornϩbed vs. NPH, Ϫ2.3 mmol/l (Ϫ3.32 to Ϫ1.29), P Ͻ 0.001), as was self-measured prebreakfast plasma glucose (P ϭ 0.006 and P ϭ 0.004, respectively). The risk of minor hypoglycemia was lower in both insulin detemir groups (25%, P ϭ 0.046; 32%, P ϭ 0.002; respectively) compared with NPH insulin in the last 12 weeks of treatment, this being mainly attributable to a 53% reduction in nocturnal hypoglycemia in the IDet mornϩbed group (P Ͻ 0.001). Although HbA 1c for each insulin detemir group was not different from the NPH group, HbA 1c for the pooled insulin detemir groups was significantly lower than for the NPH group (mean difference Ϫ0.18% [Ϫ0.34 to Ϫ0.02], P ϭ 0.027). Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups (both P Ͻ 0.001). The NPH group gained weight during the study, but there was no change in weight in either of the insulin detemir groups (IDet 12h vs. NPH, Ϫ0.8 kg [Ϫ1.44 to Ϫ0.24], P ϭ 0.006; IDet mornϩbed vs. NPH, Ϫ0.6 kg [Ϫ1.23 to Ϫ0.03], P ϭ 0.040).CONCLUSIONS -Overall glycemic control with insulin detemir was improved compared with NPH insulin. The data provide a basis for tailoring the timing of administration of insulin detemir to the individual person's needs. Diabetes Care 27:1081-1087, 2004L andmark studies show that intensive diabetes management delays progression of the late complications of type 1 diabetes (1,2). Although the introduction of rapid-acting insulin analogs has given improvement in postprandial blood glucose control, these analogs are not ideal for use with NPH insulin, which has inadequate duration of action to cover nighttime requirements and an undesirable peak effect ϳ5 h after administration (3). These problems, together with the high day-to-day variability in absorption (4,5), present a major barrier to achieving appropriate targets of blood glucose control.These limitations have stimulated the development of a soluble basal insulin analog that does not require resuspension before injection ...

Long-Acting Insulin Analogs Versus Insulin Pump Therapy for the Treatment of Type 1 and Type 2 Diabetes

“…1), a conclusion that is also supported by a systematic review of glargine (25). It is important to note that, in many cases, longacting insulin analogs, with their improved predictability and flatter absorption profile, can lower the frequency of (nonsevere) nocturnal hypoglycemia (24). This improvement with long-acting analog-based MDI in certain poorly controlled patients is part of the rationale for using a sequential treatment strategy for poorly controlled type 1 diabetes, where the efficacy of MDI is always explored before CSII (see below)-it is certainly the case that some patients are helped by best modern MDI regimens, although not usually, and unfortunately, as far as severe hypoglycemia is concerned.…”

“…In contrast, in most studies, severe hypoglycemia has not been reduced by switching to either glargine-or detemirbased MDI regimens (21)(22)(23)(24)(25) (Fig. 1), a conclusion that is also supported by a systematic review of glargine (25).…”

At last, a weight neutral insulin?

“…This produces a long-acting insulin with less variability from injection to injection and a more consistent profile, compared with other basal insulins. 25 In 6-and 12-month studies of basal-bolus therapy in type I and type II diabetes, consistent and significant favourable weight changes compared with NPH have been demonstrated [26][27][28][29][30][31][32][33] (Figure 4).…”

“…It is not surprising, therefore, that weight gain Haak et al 33 Hermansen et al 32 Home et al 31 Standl et al 30 Pieber et al 29 Russell-Jones et al 28 De Leeuw et al 27 Vague et al 26 Mean change in body weight (kg) Insulin detemir NPH insulin Months Change in weight (kg) Figure 5 Weight stability was maintained with insulin detemir for 12 months. 27 Insulin detemir and weight stability A Fritsche and H Häring S44 may be seen as an inevitable consequence of diabetes treatment, as the disease progresses over time, whatever therapy is employed to control blood glucose.…”

Insulin analogues versus human insulin in type 1 diabetes: direct and indirect meta-analyses of efficacy and safety

“…Two independent reviewers evaluated the remaining articles (see Figure 1). The remaining 16 articles for long-acting insulin analogues (glargine vs. NPH, 7; detemir vs. NPH, 7; glargine vs detemir, 2) were included in our meta-analysis A. C. C. Sanches, C. J. Correr, R. Venson, P. R. Gonçalves, M. M. Garcia, M. S. Piantavini, R. Pontarolo 504 (Garg et al, 1995;Anderson Jr. et al, 1997; Ciofetta et al, 1999;Home, 2000;Raskin, Guthrie, et al, 2000;Raskin, Klaff et al, 2000;Ratner et al, 2000;Rosenstock et al, 2000; Bode, Strange, 2001;Tamas et al, 2001; Bode et al, 2002;Devries et al, 2003;Vague et al, 2003;Hermansen et al, 2004;Porcellati et al, 2004;Russell-Jones et al, 2004;Home et al, 2004; De Leeuw et al, 2005;Fulcher et al, 2005;Home et al, 2005;Pieber et al, 2005;Home et al, 2006;Pieber et al, 2007; Bartley et al, 2008;Heller et al, 2009; Bolli et al, 2009 b).When we combined all of the studies, we counted 5,733 patients who received a short-acting insulin analog (aspart, lispro or glulisine). For lispro vs. regular, there were 954 patients; aspart vs. regular, 681; glulisine vs. regular, 240; glulisine vs. lispro, 140; glulisine vs. aspart, 112; lispro vs. aspart, 696.…”