Effects of QD insulin detemir or neutral protamine Hagedorn on blood glucose control in patients with type I diabetes mellitus using a basal-bolus regimen.

OBJECTIVE: The purpose of this trial was to compare the effects of QD basal insulin replacement using insulin detemir versus neutral protamine Hagedorn (NPH) insulin in basal-bolus therapy in combination with regular human insulin (HI) in patients with type 1 diabetes mellitus (DM). METHODS: This was a 6-month, prospective, randomized, open-label, controlled, parallel-group trial conducted at 92 sites in Europe and Australia. The trial population included men and women with type 1 DM for at least 1 year aged > or = 18 years with glycosylated hemoglobin (HbA(1c)) <== 12% already taking QD basal-bolus treatment with an intermediate- or long-acting insulin and a fast-acting human insulin or insulin analogue as bolus insulin. Patients were randomly assigned (2:1) to 6 months of treatment with insulin detemir or NPH at bedtime in combination with HI with main meals. Main outcome measures were blood glucose control as assessed by HbA(1c), fasting plasma glucose (FPG), 9-point self-monitored blood glucose (SMBG) profiles, 24-hour continuous blood glucose profiles, hypoglycemia, weight gain, and adverse events. RESULTS: Of the 749 patients randomized to treatment, 747 were exposed to trial products and included in the intent-to-treat analysis set. Seven hundred patients completed the trial: 465 (94.7%) in the insulin detemir group and 235 (91.8%) in the NPH group. After 6 months, FPG was lower with insulin detemir than with NPH (-1.16 mmol/L difference; P = 0.001), whereas HbA(1c) did not differ significantly between treatments (-0.12% [95% CI, -0.25 to 0.02]; P = NS). Day-to-day variability in self-measured fasting blood glucose was lower with insulin detemir (SD, 2.82 vs 3.60 mmol/L; P < 0.001). The overall shape of the 9-point SMBG profiles differed significantly between treatments (P = 0.006), with lower glucose levels before breakfast with insulin detemir than with NPH (P < 0.001). There was a 26% reduction in the relative risk of nocturnal hypoglycemia with insulin detemir compared with NPH (P = 0.003). Gain in body weight was significantly lower after 6 months with insulin detemir than with NPH (-0.54 kg difference; P = 0.024). The frequency and type of adverse events were similar between treatment groups. CONCLUSIONS: In this study, QD administration of insulin detemir at bedtime resulted in lower fasting blood glucose levels with less day-to-day variability and less fluctuation from ean blood glucose levels over 24 hours than NPH insulin, combined with an overall reduction in the risk of nocturnal hypoglycemia. These findings suggest that evening administration of insulin detemir may provide an opportunity to further improve fasting blood glucose targets.

Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes: a randomized clinical trial.

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 (HbA1c, prebreakfast glucose levels and variability, and hypoglycemia) and timing of administration. RESEARCH DESIGN AND METHODS: People with type 1 diabetes (n = 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(morn+bed)) 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, -1.5 mmol/l [95% CI -2.51 to -0.48], P = 0.004; IDet(morn+bed) vs. NPH, -2.3 mmol/l (-3.32 to -1.29), P < 0.001), as was self-measured prebreakfast plasma glucose (P = 0.006 and P = 0.004, respectively). The risk of minor hypoglycemia was lower in both insulin detemir groups (25%, P = 0.046; 32%, P = 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(morn+bed) group (P < 0.001). Although HbA1c for each insulin detemir group was not different from the NPH group, HbA1c for the pooled insulin detemir groups was significantly lower than for the NPH group (mean difference -0.18% [-0.34 to -0.02], P = 0.027). Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups (both P < 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, -0.8 kg [-1.44 to -0.24], P = 0.006; IDet(morn+bed) vs. NPH, -0.6 kg [-1.23 to -0.03], P = 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.