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

## TL;DR

A study found that a drug called elexacaftor-tezacaftor-ivacaftor may improve blood sugar control in adults with a type of diabetes linked to cystic fibrosis.

## Contribution

The study is the first to show a potential improvement in glycemic control with ETI in adults with established cystic fibrosis-related diabetes.

## Key findings

- ETI was associated with a 1.14 point decrease in IDAA1C after 24 months.
- ETI-treated patients showed weight gain and reduced insulin use.
- No changes were observed in the unexposed group over the same period.

## Abstract

•Cystic Fibrosis (CF) Related Diabetes (CFRD) affects 30% of people with CF (pwCF)•Elexacaftor-tezacaftor-ivacaftor (ETI) has been available for most pwCF since 2020.•A retrospective cohort study compared 39 ETI-treated pwCF to 10 unexposed pwCF.•The outcome variable was the change in Insulin Dose Adjusted Hemoglobin A1c (IDAA1C)•ETI was correlated with a 1.14 (p = 0.067) point decrease in IDAA1C after 24 months.

Cystic Fibrosis (CF) Related Diabetes (CFRD) affects 30% of people with CF (pwCF)

Elexacaftor-tezacaftor-ivacaftor (ETI) has been available for most pwCF since 2020.

A retrospective cohort study compared 39 ETI-treated pwCF to 10 unexposed pwCF.

The outcome variable was the change in Insulin Dose Adjusted Hemoglobin A1c (IDAA1C)

ETI was correlated with a 1.14 (p = 0.067) point decrease in IDAA1C after 24 months.

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

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.

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.

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.