Decreased insulin dose-adjusted hemoglobin A1c in adults with cystic fibrosis-related diabetes treated with elexacaftor-tezacaftor-ivacaftor

IF 4.2 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Clinical and Translational Endocrinology Pub Date : 2025-07-02 DOI:10.1016/j.jcte.2025.100407

Espérie Burnet , Deborah Grunewald , Etienne Larger , Florence Camus-Bablon , Catherine Eisenhauer , François Mifsud , Clémence Martin , Isabelle Honoré , Reem Kanaan , Nicolas Carlier , Johanna Fesenbeckh , Helen Mosnier-Pudar , Pierre-Régis Burgel

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Abstract

Background

Elexacaftor-tezacaftor-ivacaftor (ETI) became available for adults with cystic fibrosis (CF) in 2019, but its impact on CF-related diabetes (CFRD) remains unclear.

Methods

A single-center retrospective cohort study was conducted among adults with CFRD to examine the change in insulin dose-adjusted Hemoglobin A1c (IDAA1c). Linear mixed effects model (LMEM) analysis was used to investigate the change in IDAA1c between baseline and 24 months of follow up, comparing an ETI-treated group to an unexposed group. Baseline values were those documented at treatment initiation for the ETI-treated group and in March 2020 (±3 months) for the unexposed group.

Results

A total of 49 adults were included, 39 were treated with ETI and 10 were not. Median [Interquartile range] time since CFRD diagnosis at baseline was 13 [7–18] and 14 [10–18] years, respectively (p = 0.610). In the ETI-treated group, mean weight increased by a 4.44 kg (95 % Confidence Interval, 95 %CI: 3.08 to 5.79, p < 0.001), insulin total daily dose decreased by 5 units (95 %CI: −9 to 0, p = 0.033), and hemoglobin A1c (%) decreased by 0.65 points (95 %CI: −0.96 to −0.34, p < 0.001). No change was observed in the unexposed group. LMEM analysis found a numerically significant association between ETI and decreased IDAA1c, estimated at −1.14 points (95 %CI: −2.35 to 0.06, p = 0.067) after adjusting for age, sex, time since CFRD diagnosis and the introduction of Metformin.

Conclusion

A numerically significant association between ETI and IDAA1c decrease was observed in adults with established CFRD after 24 months of treatment, suggesting ETI contributed to improved glycemic control.

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治疗囊性纤维化相关性糖尿病成人患者胰岛素剂量调整的血红蛋白A1c

2019年，delexacaftor - tezactor -ivacaftor （ETI）开始用于囊性纤维化（CF）成人患者，但其对CF相关糖尿病（CFRD）的影响尚不清楚。方法对成年CFRD患者进行单中心回顾性队列研究，观察胰岛素剂量调整血红蛋白A1c （IDAA1c）的变化。采用线性混合效应模型（LMEM）分析研究基线和随访24个月期间IDAA1c的变化，并将eti治疗组与未暴露组进行比较。基线值是治疗组在治疗开始时和未暴露组在2020年3月（±3个月）记录的基线值。结果共纳入49例成人，其中39例经ETI治疗，10例未行ETI治疗。基线诊断CFRD的中位时间[四分位数范围]分别为13[7-18]和14[10-18]年（p = 0.610）。在eti治疗组，平均体重增加了4.44 kg(95%置信区间，95% CI: 3.08至5.79,p <；0.001)，胰岛素总日剂量降低了5个单位（95% CI: - 9 ~ 0, p = 0.033），血红蛋白A1c（%）降低了0.65点(95% CI: - 0.96 ~ - 0.34, p <；0.001)。未暴露组未观察到任何变化。LMEM分析发现，在调整年龄、性别、CFRD诊断后的时间和引入二甲双胍后，ETI和IDAA1c降低之间存在显著的数值相关性，估计为- 1.14点（95% CI: - 2.35至0.06,p = 0.067）。结论在治疗24个月后，确诊CFRD的成人患者观察到ETI与IDAA1c降低之间的数值显著相关，表明ETI有助于改善血糖控制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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