GLP-1 Hormone Infusions May Boost Insulin Production in CF Patients

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Infusions with a hormone called GLP-1 boosted insulin production in cystic fibrosis (CF) patients with impaired glucose tolerance, according to data from a small study.

The results suggest that GLP-1 agonists — medications that mimic the hormone’s activity, but last longer in the body — may be useful as an alternative to glucose injections for patients with CF-related diabetes.

That’s important because nearly half of adults with CF develop diabetes as a result of the genetic disease, studies have shown.

“Our hope is to delay or significantly reduce the need for complex insulin management through preserving [pancreas] function and insulin secretion in individuals with cystic fibrosis, potentially via a once-weekly GLP-1 agonist injection therapy,” Michael Rickels, MD, the study’s co-senior author and a professor at the Perelman School of Medicine at University of Pennsylvania, said in a university press release.

The study, “Effects of GLP-1 and GIP on Islet Function in Glucose Intolerant, Pancreatic Insufficient Cystic Fibrosis,” was published in the journal Diabetes.

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Cystic fibrosis is characterized by the buildup of abnormally sticky and thick mucus in various organs, notably the lungs and pancreas. The pancreas, which sits behind the stomach, produces insulin, a hormone that helps the body’s cells take up glucose (sugar) in the blood.

The hallmark of CF-related diabetes, meanwhile, is the reduced production of insulin in the body; a possible abnormal response to insulin also may occur.

“[Because] diabetes has been linked to worse lung function, this creates a vicious cycle, with diabetes acting as a multiplier on the patient’s already damaged lungs,” the release stated.

Normally after a meal, the gut releases hormones called incretins, which signal the pancreas to produce insulin. There are two main incretins: GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide).

This study enrolled 32 CF patients with abnormal glucose tolerance and pancreatic insufficiency, a key digestive symptom of CF. Four CF patients with normal glucose tolerance and four people without CF also were included as controls.

The study participants were given 90-minute infusions with incretins — half with GLP-1, and half with GIP. The patients each received two infusions, one with the active hormone, and another with a placebo to serve as a comparator.

Results showed that, among the CF patients, natural insulin production was increased when given infusions of the GLP-1 hormone, compared with placebo infusions. However, infusions of GIP did not boost insulin production.

“These data indicate that GLP-1, but not GIP, augments glucose-dependent insulin secretion in [CF patients with pancreatic insufficiency], supporting the likelihood that GLP-1 agonists could have therapeutic benefit in this population,” the researchers concluded.

“This finding supports the likelihood that GLP-1 agonist medications could have therapeutic benefit in the treatment and possible prevention of cystic fibrosis-related diabetes,” Rickels said, adding that a proof-of-concept clinical trial testing once-weekly treatment with an available GLP-1 agonist is ongoing.

Further study to understand why GIP does not have insulin-boosting effects in people with CF could help to shed light on the biological underpinnings of how CF-related diabetes develops, the researchers also noted.