Repaglinide versus insulin for newly diagnosed diabetes in patients with cystic fibrosis: a multicentre, open-label, randomised trial
Repaglinide versus insulin for newly diagnosed diabetes in patients with cystic fibrosis: a multicentre, open-label, randomised trial
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DOI：
10.1016/s2213-8587(17)30400-x
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发表时间：
2018-02-01
影响因子：
44.5
通讯作者：
Holl, Reinhard W.
中科院分区：
文献类型：
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作者：
Ballmann, Manfred;Hubert, Dominique;Holl, Reinhard W.
背景 随着近几十年来囊性纤维化患者的生存率有所提高，并发症也变得越来越重要。最常见的并发症是囊性纤维化相关的糖尿病。推荐的治疗方法是注射胰岛素，但也有一些患者采用口服降糖药物进行治疗，以减轻治疗负担。我们评估了口服抗糖尿病药物的有效性和安全性。& para;& para;方法 我们在奥地利、法国、德国和意大利的 49 个中心进行了一项多中心、开放标签、比较、随机试验。符合条件的患者患有囊性纤维化，年龄超过 10 岁，并且患有新诊断的糖尿病。我们使用源自 Geigy 随机数表的中央随机化方案，以 1:1 的比例将患者分配至接受胰岛素或瑞格列奈治疗，并按性别和年龄（10-15 岁或 >15 岁）分层。主要结局是通过治疗 24 个月后 HbA1c 浓度相对于基线的平均变化来评估血糖控制。通过线性模型评估组间差异。主要分析和安全性分析是在修改后的意向治疗人群（包括因缺乏疗效而提前停止治疗的患者）中进行的。该试验在 ClinicalTrials.gov 注册，编号为 NCT00662714。 结果 我们招募了瑞格列奈组 34 名患者和胰岛素组 41 名患者，其中分别包括 30 名和 37 名患者纳入分析。 24 个月时，瑞格列奈组和胰岛素组的血糖控制相似（瑞格列奈组 HbA k 浓度相对于基线的平均变化为 0.2% [SD 0.7%]、1.7 mmol/mol [8.1 mmol/mol]，而胰岛素组为 -0.2% [1.3%]、-2.7 mmol/mol、[14.5 mmol/mol]；组间平均差异为 -0.4%，（95% CI -1.1 至 0.2 [-4.4 mmol/mol，-11.5 至 2.7]，1:0.1.5），最常见的不良事件是肺部事件（瑞格列奈组 107 例中 43 例 [40%]，胰岛素组 133 例中 60 例 [45%]），最常见的严重不良事件是导致入院的肺部事件（10 例和 7 例中 5 例 [50%]）。 [分别为 13 人中的 54%1]。& para;& para;解释 瑞格列奈用于控制囊性纤维化相关糖尿病患者的血糖与胰岛素一样有效和安全。
Background As survival among patients with cystic fibrosis has improved in recent decades, complications have become increasingly relevant. The most frequent complication is cystic-fibrosis-related diabetes. The recommended treatment is injected insulin, but some patients are treated with oral antidiabetic drugs to ease the treatment burden. We assessed the efficacy and safety of oral antidiabetic drugs.& para;& para;Methods We did a multicentre, open-label, comparative, randomised trial in 49 centres in Austria, France, Germany, and Italy. Eligible patients had cystic fibrosis, were older than 10 years, and had newly diagnosed diabetes. We used a central randomisation schedule derived from a Geigy random number table to assign patients 1:1 to receive insulin or repaglinide, stratified by sex and age (10-15 years or >15 years). The primary outcome was glycaemic control assessed by mean change in HbA,, concentration from baseline after 24 months of treatment. Differences between groups were assessed by linear models. The primary and safety analyses were done in the modified intention-to-treat population (including patients who stopped treatment early because of lack of efficacy). This trial is registered with ClinicalTrials.gov, number NCT00662714.& para;& para;Findings We enrolled 34 patients in the repaglinide group and 41 in the insulin group, of whom 30 and 37, respectively, were included in the analyses. M 24 months, glycaemic control was similar in the repaglinide and insulin groups (mean change in HbA k concentration from baseline 0.2% [SD 0.7%], 1.7 mmol/mol [8.1 mmol/mol] with repaglinide vs -0.2% [1.3%], -2.7 mmol/mol, [14.5 mmol/mol] with insulin; mean difference between groups -0.4%, (95% CI -1.1 to 0.2 [-4.4 mmol/mol, -11.5 to 2.7], 1:0.1.5). The most frequent adverse events were pulmonary events (43 [40%] of 107 in the repaglinide group and 60 [45%] of 133 in the insulin group), and the most frequent serious adverse events were pulmonary events leading to hospital admission (five [50%] of ten and seven [54%1 of 13, respectively).& para;& para;Interpretation Repaglinide for glycaemic control in patients with cystic-fibrosis-related diabetes is as efficacious and safe as insulin.