Medical Clinic, Villecresnes, France.
Diabetes Care. 2009 Jan;32(1):32-7. doi: 10.2337/dc08-0332. Epub 2008 Oct 22.
The purpose of this study was to compare effects of insulin detemir once daily versus twice a day in a basal-bolus insulin regimen.
In this open-label, 7-month study, 520 patients with type 1 diabetes were randomly assigned to receive detemir once daily or twice daily with mealtime insulin aspart. Insulin doses were titrated over 1 month, with patients followed up over the subsequent 3 months. Thereafter, patients were able to switch from one regimen to the other, with an additional nonrandomized 3-month follow-up, to a total of 7 months. The primary end point was A1C at 4 months, with noninferiority defined as a difference <0.4% between groups.
A1C at 4 months was 8.1 +/- 0.9 versus 8.0 +/- 1.0% with once- and twice-daily detemir, respectively, with an adjusted between-group difference of 0.12% (95% CI -0.01 to 0.25%), showing noninferiority for once-daily dosing. Similar results were found in the per protocol population. Improvement in A1C was similar in both groups (-0.4 +/- 0.8 vs. -0.5 +/- 0.8%; P = 0.09, NS) but with differences in the 7-point glucose profile. Detemir doses were lower (29 +/- 18 vs. 39 +/- 20 units/day, P < 0.001), but aspart doses were higher (34 +/- 17 vs. 26 +/- 14 IU/day, P < 0.001) with once-daily detemir. At 7 months, A1C decreased slightly in patients switched from once-daily to twice-daily administration (8.2 +/- 0.8 vs. 8.0 +/- 0.8%; P = 0.34, NS) in association with increased total insulin doses (P < 0.05), but A1C increased in those switched from twice-daily to once-daily administration (7.2 +/- 0.9 vs. 7.6 +/- 0.8%, P < 0.05) in association with decreased doses (P < 0.05).
Although some individuals may benefit from twice-daily dosing, the most suitable routine starting schedule for detemir in a basal-bolus regimen for type 1 diabetes is once-daily injection.
本研究旨在比较每日 1 次和每日 2 次胰岛素地特胰岛素在基础-餐时胰岛素方案中的疗效。
这是一项开放标签、7 个月的研究，共纳入 520 例 1 型糖尿病患者，随机分为每日 1 次地特胰岛素组和每日 2 次地特胰岛素组，联合餐时门冬胰岛素治疗。经过 1 个月的胰岛素剂量滴定，患者随后随访 3 个月。此后，患者可从一种方案转换为另一种方案，同时进行额外的非随机 3 个月随访，总随访时间为 7 个月。主要终点为 4 个月时的糖化血红蛋白（A1C），定义组间差异<0.4%为非劣效性。
每日 1 次和每日 2 次地特胰岛素组的 A1C 分别为 8.1±0.9%和 8.0±1.0%，调整组间差异为 0.12%（95%CI-0.01 至 0.25%），表明每日 1 次给药具有非劣效性。在符合方案人群中也得到了相似的结果。两组的 A1C 改善情况相似（-0.4±0.8% vs. -0.5±0.8%；P=0.09，NS），但 7 点血糖谱存在差异。每日 1 次地特胰岛素组的地特胰岛素剂量较低（29±18 比 39±20 单位/天，P<0.001），但门冬胰岛素剂量较高（34±17 比 26±14IU/天，P<0.001）。在 7 个月时，从每日 1 次转换为每日 2 次给药的患者 A1C 略有下降（8.2±0.8%比 8.0±0.8%；P=0.34，NS），同时总胰岛素剂量增加（P<0.05），但从每日 2 次转换为每日 1 次给药的患者 A1C 升高（7.2±0.9%比 7.6±0.8%，P<0.05），同时剂量减少（P<0.05）。
尽管一些患者可能从每日 2 次给药中获益，但对于 1 型糖尿病患者的基础-餐时胰岛素方案，地特胰岛素最适合的起始方案为每日 1 次注射。
