GLP-1s may boost lung function for CF-related diabetes patients
Small study shows significant gains after 1 year of treatment
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GLP-1 receptor agonists (GLP-1RAs), medications commonly used for diabetes and weight loss, may improve lung function in adults with cystic fibrosis-related diabetes (CFRD), according to a small, exploratory study from Australia.
After one year of treatment, patients given a GLP-1RA in addition to insulin, the standard CFRD treatment, had significant gains in two lung function measures relative to those not on these medications. GLP-1RA treatment was also associated with better blood sugar control, reduced insulin requirements, less time with low blood sugar, and weight loss.
“Our exploratory observations are potentially important but require confirmation in [appropriately controlled] trials,” the researchers wrote.
The study, “Glucagon-Like Peptide-1 Receptor Agonist Use Is Associated With Improved Lung Function in Cystic Fibrosis-Related Diabetes,” was published as a research letter in the journal Diabetes, Obesity and Metabolism.
Cystic fibrosis (CF), characterized by impaired or absent CFTR activity, has historically been associated with progressive loss of lung function. However, 40%–50% of patients develop CFRD, characterized by reduced production of insulin, a hormone that controls blood sugar levels. CFRD patients may also develop a reduced response to insulin (insulin resistance).
Inadvertent effects
Current guidelines recommend insulin as the standard treatment for CFRD because it has lung benefits and can help increase body weight, which is traditionally reduced in people with CF due to poor gastrointestinal absorption and reduced appetite.
However, by restoring CFTR function, highly effective CFTR modulator therapies have inadvertently increased rates of obesity and insulin resistance. That makes treatments that improve blood sugar control while reducing excess weight particularly useful.
GLP-1RAs are a class of diabetes and weight-loss medicines. Preclinical work suggests GLP-1 signaling could have beneficial effects on airway muscle, mucus production, and lung inflammation. Data from a few CFRD cases on GLP-1Ra treatment have also suggested lung function improvements.
The researchers set out to evaluate whether adding a GLP-1RA to insulin therapy was associated with lung function changes in adults with CFRD, while also examining measures of diabetes control.
By retrospectively reviewing data from 230 adults with CF treated at a single center from 2021 to 2024, they identified 10 CFRD patients receiving a GLP-1RA plus insulin and 15 CFRD patients on insulin alone (control group).
The groups were matched for age and use of the CFTR modulator Trikafta (elexacaftor/tezacaftor/ivacaftor). However, body weight and body mass index (BMI), a ratio of weight and height commonly used as a proxy of body fat, were significantly higher in the GLP-1RA group.
The most commonly used GLP-1RA (in eight of the 10 patients) was semaglutide (sold under the brand names Ozempic, Wegovy, and Rybelsus), followed by dulaglutide (sold as Trulicity) and liraglutide (sold as Victoza and others, with generics available).
During the two years before the study’s start (baseline), lung function remained stable in both groups.
After 12 months of GLP-1RA treatment, median forced expiratory volume in one second (FEV1) — the amount of air a person can forcefully exhale in one second — increased significantly, by 170 mL, equivalent to a 6% improvement in predicted FEV1. Forced vital capacity (FVC), the total amount of air that can be forcefully exhaled, also increased significantly by 100 mL, or by 3% in predicted FVC.
Changes in both FEV1 and FVC differed significantly between GLP-1RA-treated participants and those receiving standard care.
GLP-1RA was also associated with improvements in several measures of diabetes control. These included a 1.9% median reduction in blood levels of HbA1c, a measure of average blood sugar over two to three months. HbA1c did not change significantly in the control group.
At six months, time spent within the target glucose (blood sugar) range increased by 29% in the GLP-1RA group and by 7% in the control group. Median daily insulin dose fell by 11 units with GLP-1RA treatment, but was unchanged with standard care. The GLP-1RA group also spent significantly less time with glucose below the target range compared with the control group.
Body weight fell by a median of 4.1 kg (about nine pounds) after 12 months of GLP-1RA therapy, while it increased by a median of 2 kg (about 4.4 pounds) with standard care.
Three GLP-1RA-treated participants reported nausea, but none stopped treatment because of it. One person with a history of repeated bowel obstructions was hospitalized for another obstruction, recovered, and later restarted semaglutide without recurrence. Another person discontinued GLP-1RA because of difficulty consuming enough calories while training for a marathon.
“That we observed a greater increase in FEV1 than FVC suggests that an additional mechanism may have contributed to the observed FEV1 improvement other than weight reduction, which is typically mediated by FVC,” the researchers wrote. “Other potential mediators include improved [blood sugar] control, direct effects of GLP-1RA on the lung, and reduced inflammation.”
The investigators cautioned that differences between groups at the study’s start could have influenced the results, and that more studies are needed to validate the findings.
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