Davies M, Evans R, Storms F, Gomis R, Khunti K
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Diabetes Obes Metab. 2007 Sep;9(5):706-13. doi: 10.1111/j.1463-1326.2006.00652.x.
The AT.LANTUS study compared insulin glargine initiation and titration using one of two algorithms in suboptimally controlled subjects with type 2 diabetes mellitus (T2DM) based on a primary outcome of severe hypoglycaemia. Secondary outcomes included other categories of hypoglycaemia, glycaemic control, weight changes and insulin dose. Here, we report the results of a subanalysis of the trial, which investigated whether insulin glargine can be initiated and titrated as effectively in primary [general practitioner (GP)] as secondary (hospital) care in patients with T2DM in the UK.
The main study was a multicentre (n = 611), multinational (n = 59), open-label, 24-week randomized trial in 4,588 suboptimally controlled subjects with T2DM. Insulin glargine was titrated to target fasting blood glucose (FBG) levels of <or=5.5 mmol/l according to algorithm 1 (clinic-driven titration) or algorithm 2 (patient-managed titration). In this substudy, 819 subjects (GP, n = 215; hospital, n = 604) from 57 primary and 130 secondary care centres were included in the subanalysis; subjects were switched to once-daily insulin glargine from baseline treatments that consisted primarily of oral antidiabetic agents (OADs) (38%) only or premixed insulin +/- OAD (23%).
Both the GP and the hospital groups of subjects experienced a low incidence of severe hypoglycaemia (<1%), with significant decreases in HbA1c levels (-0.51 and -0.95% respectively; p < 0.001), large reductions in FBG levels (-2.72 and 3.0 mmol/l respectively; p < 0.001) and modest weight gain of 1 and 1.2 kg respectively (p < 0.05). With the exception of absolute reductions in HbA1c and reductions in basal and prandial insulin made on switching to insulin glargine, there were few significant differences in subjects managed in primary compared with secondary care.
This study shows that despite differences in diabetes duration and baseline glycaemic control, an insulin glargine-based therapy can be safely and effectively initiated in a diverse range of suboptimally controlled subjects with T2DM in both primary and secondary care settings in the UK. Rates of hypoglycaemia were low and consistent with the results of the main study. Absolute reductions in HbA1c were greatest in the secondary care setting, but similar levels of glycaemic control were achieved in both groups due to differences in baseline HbA1c. In the patients managed in primary care, there was an overall reduction in prandial and basal insulin used when switching to a basal insulin regimen and a lack of titration of prandial insulin. Therefore, the role of prandial insulin, its initiation and titration, appears to be an area that requires more focus in primary care.
AT.LANTUS研究基于严重低血糖这一主要结局，比较了在血糖控制欠佳的2型糖尿病（T2DM）患者中使用两种算法之一起始和滴定甘精胰岛素的情况。次要结局包括其他类型的低血糖、血糖控制、体重变化和胰岛素剂量。在此，我们报告该试验的一项亚组分析结果，该分析调查了在英国T2DM患者中，甘精胰岛素在初级保健[全科医生（GP）]和二级保健（医院）中起始和滴定的效果是否相同。
主要研究是一项多中心（n = 611）、跨国（n = 59）、开放标签、为期24周的随机试验，纳入4588例血糖控制欠佳的T2DM患者。根据算法1（诊所驱动滴定）或算法2（患者自我管理滴定），将甘精胰岛素滴定至空腹血糖（FBG）目标水平≤5.5 mmol/L。在这项亚研究中，来自57个初级保健中心和130个二级保健中心的819例患者（GP组，n = 215；医院组，n = 604）纳入亚组分析；患者从主要由口服降糖药（OADs）（38%）或预混胰岛素±OAD（23%）组成的基线治疗转换为每日一次的甘精胰岛素治疗。
GP组和医院组患者严重低血糖发生率均较低（<1%），糖化血红蛋白（HbA1c）水平显著降低（分别降低-0.51%和-0.95%；p < 0.001），FBG水平大幅降低（分别降低-2.72和3.0 mmol/L；p < 0.001），体重分别适度增加1 kg和1.2 kg（p < 0.05）。除了转换为甘精胰岛素后HbA1c的绝对降低以及基础胰岛素和餐时胰岛素的减少外，初级保健管理的患者与二级保健管理的患者之间几乎没有显著差异。
本研究表明，尽管糖尿病病程和基线血糖控制存在差异，但在英国，基于甘精胰岛素的治疗在初级保健和二级保健环境中，均可在多种血糖控制欠佳的T2DM患者中安全有效地起始。低血糖发生率较低，与主要研究结果一致。二级保健环境中HbA1c的绝对降低幅度最大，但由于基线HbA1c的差异，两组血糖控制水平相似。在初级保健管理的患者中，转换为基础胰岛素方案时，餐时胰岛素和基础胰岛素的使用总体减少，且餐时胰岛素未进行滴定。因此，餐时胰岛素的作用、其起始和滴定似乎是初级保健中需要更多关注的领域。
