GLP-1 agonists, a class of drugs originally intended to address type 2 diabetes, have proven to induce significant weight loss while also showing promise for addressing asthma in overweight patients.
“There’s an unmet need for next-generation asthma treatments that don’t contain steroids and will address the unique inflammatory pathways seen in those with asthma and obesity,” said Katherine Cahill, M.D., an assistant professor of medicine at Vanderbilt University Medical Center.
“The work with these drugs has underscored that metabolic pathways are important in good lung health, although until recently we’d never thought to treat lung disease by targeting them.”
A March 2023 article in the Journal of Pulmonary Therapy that was co-authored by Cahill discusses using GLP-1 agonists to treat asthma in people with comorbid obesity.
Obesity and Asthma Tightly Knit
Obesity is a major risk factor for asthma. It often precedes the onset of asthma and is associated with increased severity of symptoms, Cahill said.
“Obesity changes the type of inflammation in the lung in such a way that it is often less responsive to conventional therapies,” she added.
In the United States, 7.1 percent of lean adults (BMI <25) have asthma as compared to 11.1 percent of obese adults (BMI ≥30).
In phase 3 clinical trials using GLP-1 agonists, weight loss beyond 15 percent of total body weight in one year was achieved when paired diet and exercise, Cahill said.
“These results mean physicians finally have a viable medical option for addressing the obesity epidemic,” she said.
People Breathe Easier
Earlier research by Cahill and others showed that GLP-1 agonists reduce airway inflammation in mice.
“My colleagues gave the drugs to mice before exposing the mice to molds or dust mites which are common asthma triggers, and the drugs improved features important in asthma,” she said.
To consider the effects in humans, her group looked at clinical datasets to determine whether the drugs might reduce asthma symptoms in people with asthma and type 2 diabetes, as well. That study measured asthma exacerbation and the need for steroids over the six months following the drug treatment’s initiation.
The researchers analyzed data on 5,940 patients taking GLP-1 agonists, SGLT-2 inhibitors, DPP-4 inhibitors, sulfonylureas or insulin. After six months, asthma exacerbations were lower in patients taking GLP-1 agonists compared to the other four types of medications.
“Subsequent observational studies have shown that patients treated with a GLP-1 agonist also had fewer health care encounters, including fewer trips to the emergency department or hospitalizations for their respiratory disease,” Cahill said.
Clinical trials to confirm whether GLP-1 agonists improve asthma in patients with obesity are underway, including at Vanderbilt under Cahill’s leadership.
Sky-high Interest
Before GLP-1 agonists became available, effective medical treatments for obesity were limited.
“The weight loss results with these drugs have attracted lots of attention – not just in medical circles but also among the rich and famous,” Cahill said.
Famous personalities such as Elon Musk tout the new drugs’ value for weight control – even those who don’t appear to meet clinical criteria for a prescription. This kind of boutique use – and the fact that nearly half the U.S. adult population meets eligibility criteria for clinical use of the drugs – has prompted demand to outstrip supply.
“Colleagues contact me weekly about stories they’ve seen in the lay press discussing these medications,” Cahill said.
Dual Benefits Possible
Cahill said her team believes the drugs will benefit patients’ airways with their anti-inflammatory effects, in addition to promoting weight loss.
“These improvements could allow many patients to initiate exercise routines that had been too hard for them previously, because of their asthma,” Cahill said.
“I highlight to patients that a 5 to 10 percent reduction in weight can bring noticeable improvements in their asthma without additional medications.”
In contrast to the new drugs, older asthma medications have induced weight gain, adding stress to the joints and discouraging exercise.
“I highlight to patients that a 5 to 10 percent reduction in weight can bring noticeable improvements in their asthma without additional medications,” Cahill said. “I stress that the lungs need exercise just like the heart, and it doesn’t have to be intense or last for long periods of time to be valuable. When they hear that, people often find it motivating.”
