Elexacaftor–tezacaftor–ivacaftor (ETI) is a highly effective modulator therapy associated with significant improvements in respiratory function and quality of life among people living with cystic fibrosis (CF). However, ETI has also been shown to result in significant weight gain and there is emerging interest regarding traditional cardiometabolic risk factors. This systematic review investigated the effects of ETI on cardiometabolic risk factors (obesity/overweight, body composition, glucose metabolism, lipids, blood pressure and bone parameters) in people living with CF. This review adhered with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and was registered in PROSPERO (CRD42025630118). The following databases were searched in December 2024 and June 2025: PubMed, Scopus, Web of Science and Embase. A total of 54 publications met inclusion criteria (including ETI treatment duration >4 months, >10 total participants, empirical studies) and underwent data extraction. Risk of bias was assessed using National Institutes of Health tools. Results were prepared in tabular format and narrative summary. There was notable heterogeneity in study design and results. In published studies to date, ETI initiation was generally followed by a decrease in glycated haemoglobin, but minimal change in other glycaemic or insulinaemic parameters. Some studies reported increased blood pressure, hypertension and overweight/obesity classification, and cholesterol levels. The observational design and short duration of most studies limit the ability to conclude direct effects of ETI, particularly in the long term. However, we conclude there is likely increased risk of certain traditional cardiometabolic risk factors in ageing people with CF, thus highlighting the importance of clinical surveillance and prompt intervention if needed.
Girouard et al. (Thu,) studied this question.