Impact of Elexacaftor/Tezacaftor/Ivacaftor on Glucose Tolerance and Abnormal Glucose Metabolism: A Phase 3b, Open-Label Clinical Trial.

Elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) is safe and effective for people with CF ≥2 years of age with ELX/TEZ/IVA-responsive CFTR (CF transmembrane conductance regulator) mutations; however, efficacy on glycemic control has not been studied.

Elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) 对于2岁及以上的CF患者是安全有效的，这些患者携带有ELX/TEZ/IVA反应性的CFTR（囊性纤维化跨膜传导调节器）突变；然而，其对血糖控制的疗效尚未被研究。

Objectives: To evaluate the impact of ELX/TEZ/IVA on glucose tolerance in people with CF who have IGT or CFRD.

目的：评估ELX/TEZ/IVA对患有CF且存在IGT或CFRD患者的葡萄糖耐受性的影响。

Methods: In this phase 3b, open-label study, ELX/TEZ/IVA was administered for 48 weeks to participants ≥12 years of age, heterozygous for F508del and a minimal function CFTR mutation, with either IGT or CFRD.

方法：在这项3b期、开放标签的研究中，对年龄≥12岁、携带F508del和一个最小功能CFTR突变的杂合子参与者，无论是IGT还是CFRD，均给予ELX/TEZ/IVA治疗48周。

Measurements and Main Results: Sixty-nine participants received ELX/TEZ/IVA.

测量和主要结果：69名参与者接受了ELX/TEZ/IVA治疗。

The primary endpoint was change in blood glucose concentration after a 2-hour oral glucose tolerance test from baseline to the average of Week 36 and Week 48; participants had a mean change of -35.0 mg/dl (95% confidence interval[CI], -49.2 to -20.7 mg/dl; P < 0.0001) (-1.9 mmol/L [95% CI, -2.7 to -1.2 mmol/L]).

主要终点是2小时口服葡萄糖耐量试验后，从基线到第36周和第48周平均值的血糖浓度变化；参与者平均变化为-35.0 mg/dl（95%置信区间[CI]，-49.2至-20.7 mg/dl；P < 0.0001）（-1.9 mmol/L [95% CI, -2.7至-1.2 mmol/L]）。

Secondary endpoints were the proportion of participants with improvement in dysglycemia categorization (CFRD, IGT, normal glucose tolerance) at Week 48 and safety.

次要终点是第48周时参与者在糖尿病分类（CFRD，IGT，正常葡萄糖耐受）改善的比例以及安全性。

Among participants with abnormal glucose tolerance at baseline, 37.7% (95% CI, 24.8 to 52.1) had improvements in dysglycemia categorization at Week 48.

在基线时有异常葡萄糖耐受的参与者中，37.7%（95%置信区间，24.8至52.1）在第48周时糖尿病分类有所改善。

Overall, 35.5% of participants had normal glucose tolerance at Week 48 compared with 13.0% at baseline.

总体而言，第48周时有35.5%的参与者表现出正常的葡萄糖耐受，而基线时这一比例为13.0%。

Safety was consistent with the established safety profile of ELX/TEZ/IVA.

安全性与ELX/TEZ/IVA已知的安全性特征一致。

Conclusions: ELX/TEZ/IVA treatment led to clinically meaningful improvements in blood glucose regulation, with significant within-group decreases in blood glucose concentrations after oral glucose tolerance testing and improved dysglycemia categorization in people with CF with early IGT or CFRD.

结论：ELX/TEZ/IVA治疗在血糖调节方面带来了临床意义上的改善，口服葡萄糖耐量测试后血糖浓度显著下降，并改善了早期糖耐量受损或囊性纤维化相关糖尿病患者的血糖异常分类。

Clinical trial registered with www.clinicaltrials.gov (NCT04599465).

临床试验已注册于www.clinicaltrials.gov (NCT04599465)。