People taking GLP-1 receptor agonists appeared to be at elevated risk of rejection episodes after lung transplantation, a small, single-center cohort study suggested.

In a retrospective review of 301 consecutive lung transplants, the 34 lung recipients taking a GLP-1 drug for diabetes or obesity early in their post-transplant course had 15.19-fold (95% CI 2.08-23.55, P<0.05) greater adjusted odds of antibody-mediated rejection compared with non-users.

There was also a numerical trend for more chronic rejection diagnosed as bronchiolitis obliterans syndrome with GLP-1 drug prescription (adjusted OR 2.49, 95% CI 0.478-12.997, P=0.279), reported Zehra Dhanani, MBBS, of Temple University Hospital in Philadelphia, during the International Society for Heart and Lung Transplantation annual meeting in Boston.

With the rapid increase in GLP-1 receptor agonist use in the population more broadly, “without any surprise, we are seeing an increase in the number of patients who are on GLP-1 receptor agonists after transplantation,” Dhanani told MedPage Today. “Some of the medications that these transplant patients get for their immunosuppression after transplant also increases their risk for diabetes. So, inadvertently, they end up being on these medications.”

“One of the mechanisms of action that GLP-1 works by is by delaying gastric emptying,” she added. “And that essentially raised the question for us … is that gastric emptying leading to more aspiration events, which is one of the bigger risk factors for allograft dysfunction in lung transplant patients?”

Given its small size and observational design, the study couldn’t determine causality and shouldn’t change practice, Dhanani acknowledged.

“We’ve seen hints of it. With a better, larger study, we may see something real out there,” Dhanani noted. “A multicenter retrospective or a prospective study would honestly make a huge difference.”

Meanwhile, “I think it’s enough to make us ask the question,” she said. “A lot of physicians are doing things based on their personal experiences, but right now these data are not sufficient to change practice. I personally start 6 months later, but I wouldn’t say that all of Temple does.”

The first 6 months after lung transplantation is a particularly vulnerable period for aspiration-related harms, she noted.

Importantly, the study showed a similar trend towards reduced mortality (adjusted OR 0.308, 95% CI 0.047-2.01) in patients who were on a GLP-1 medication as that seen in pivotal trials in other patient populations. “There is a mortality benefit and we see it here as well,” Dhanani said. “It’s a good drug, but what is a safe time to start the medication? Because the risk of aspiration is in the early post-transplant period. So maybe it’s an excellent drug to employ, but maybe not in the first 6 months.”

The study involved retrospective review of all 301 consecutive lung transplant recipients at Temple University Hospital over the period from 2016 to 2022.

Among the participants, 34 started a GLP-1 receptor agonist early on in their transplant course, within the first 2 years after transplant (average 318 days post-transplant). They were compared with non-users in a model with multivariate logistic regression to control for all known confounding factors that contribute to chronic lung allograft dysfunction.

The most commonly used GLP-1 drugs were dulaglutide (Trulicity; 23 patients) and semaglutide (Ozempic, Wegovy; 11 patients).

The overall cohort had an average age of 65, 32% were women, and about 85% were white. Nearly one in five patients had diabetes. Average body mass index (BMI) was 27.

Double lung transplant was performed in 22% of patients. The etiology of indication for transplant was chronic obstructive lung disease in 34%, idiopathic pulmonary fibrosis in 35%, and combined pulmonary fibrosis and emphysema in about 8%.

“This is a fairly representative population for lung transplant patients,” Dhanani noted. “There’s a very good mix of different etiologies of transplant, different age groups, BMI.”

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