Paediatric Clinic, University Medicine Rostock, Rostock, Germany; Clinic for Paediatric Pulmonology, Allergy, and Neonatology, Medical School Hannover, Hannover, Germany.
Department of Respiratory Disease and Adult Cystic Fibrosis Centre, Cochin Hospital APHP, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Lancet Diabetes Endocrinol. 2018 Feb;6(2):114-121. doi: 10.1016/S2213-8587(17)30400-X. Epub 2017 Dec 5.
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.
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.
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. At 24 months, glycaemic control was similar in the repaglinide and insulin groups (mean change in HbA 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], p=0·15). 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%] of 13, respectively).
Repaglinide for glycaemic control in patients with cystic-fibrosis-related diabetes is as efficacious and safe as insulin.
Mukoviszidose eV, Vaincre la Mucoviscidose, ABCF Association, and Novo Nordisk.
近几十年来，囊性纤维化患者的存活率有所提高，因此并发症变得越来越重要。最常见的并发症是囊性纤维化相关糖尿病。推荐的治疗方法是注射胰岛素，但有些患者使用口服降糖药来减轻治疗负担。我们评估了口服降糖药的疗效和安全性。
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、对照、随机试验。合格的患者患有囊性纤维化，年龄大于 10 岁，且新诊断为糖尿病。我们使用中央随机分组方案（源自 Geigy 随机数表），按照性别和年龄（10-15 岁或>15 岁）将患者 1:1 随机分配接受胰岛素或瑞格列奈治疗。主要结局是治疗 24 个月后 HbA1c 浓度的平均变化评估的血糖控制情况。组间差异通过线性模型进行评估。主要和安全性分析在改良意向治疗人群中进行（包括因疗效不佳而提前停止治疗的患者）。该试验在 ClinicalTrials.gov 注册，编号为 NCT00662714。
我们招募了 34 名瑞格列奈组和 41 名胰岛素组的患者，其中分别有 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情况相似（瑞格列奈组 HbA1c 浓度自基线的平均变化为 0.2%[7.0%]，1.7mmol/mol[8.1mmol/mol]，胰岛素组为-0.2%[1.3%]，-2.7mmol/mol[14.5mmol/mol]；组间平均差异为 0.4%（95%CI -1.1 至 0.2[-4.4mmol/mol，-11.5 至 2.7]，p=0.15）。最常见的不良事件是肺部事件（瑞格列奈组 107 例中有 43 例[40%]，胰岛素组 133 例中有 60 例[45%]），最常见的严重不良事件是导致住院的肺部事件（瑞格列奈组 5 例[50%]，胰岛素组 7 例[54%]）。
瑞格列奈治疗囊性纤维化相关糖尿病的血糖控制效果与胰岛素一样有效且安全。
Mukoviszidose eV、Vaincre la Mucoviscidose、ABCF 协会和诺和诺德。
