medwireNews: Patients with chronic obstructive pulmonary disease (COPD) and type 2 diabetes experience fewer exacerbations with glucagon-like peptide (GLP)-1 receptor agonists than with other medications targeting glucose metabolism, US research suggests.
Writing in the American Journal of Respiratory and Critical Care Medicine, Dinah Foer (Brigham and Women’s Hospital, Boston, Massachusetts) and co-authors say their “findings may inform treatment choices for patients with comorbid COPD and [type 2 diabetes], reducing morbidity from exacerbations and from corticosteroids used to treat exacerbations.”
They reviewed electronic health record data for 1642 patients (median age 70 years, 61% men) with COPD who initiated treatment with a GLP-1 receptor agonist (n=328), dipeptidyl peptidase (DPP)-4 inhibitor (n=260), sodium-glucose cotransporter (SGLT)2 inhibitor (n=353), or sulfonylurea (n=701) between 2012 and 2022.
During the first 6 months after the index prescription, 23.2% of participants given a GLP-1 receptor agonist experienced at least one moderate exacerbation, compared with 27.3%, 24.1%, and 31.4% of those given a DPP-4 inhibitor, SGLT2 inhibitor, and sulfonylurea, respectively. The corresponding rates for severe exacerbations were 8.8%, 15.0%, 12.2%, and 17.8%.
After adjustment for potential clinical confounders such as age, sex, race, smoking history, metformin use, and COPD medications, the researchers observed that people taking a DPP-4 inhibitor or a sulfonylurea were significantly more likely to have a new moderate or severe exacerbation than those given a GLP-1 receptor agonist, at incidence rate ratios (IRR) of 1.48 and 2.09, respectively.
Additional adjustment for metabolic confounders, namely baseline BMI and glycated hemoglobin level, attenuated the difference between GLP-1 receptor agonist and DPP-4 inhibitor users, but the IRR remained significantly elevated among sulfonylurea users, at 1.97.
Across both multivariate models, there was no significant difference in exacerbation incidence between GLP-1 receptor agonists and SGLT-2 inhibitors.
Considering just moderate exacerbations, the team found that both DPP-4 inhibitor and sulfonylurea users had a significantly higher risk than GLP-1 receptor agonist users after adjustment for the clinical confounders, at hazard ratios (HR) of 1.52 and 2.09, respectively.
The risk for severe exacerbations was similarly elevated, at corresponding HRs of 1.85 and 2.21.
In the metabolic model, the risk for moderate exacerbations remained significantly increased for sulfonylurea users only (HR=1.92) versus GLP-1 receptor agonist users, whereas the risk for severe exacerbations was significantly elevated for both DPP-4 inhibitor (HR=2.04) and sulfonylurea (HR=2.63) users.
The team also analyzed the data by BMI subgroup and found that among people with obesity DPP-4 inhibitor users or sulfonylurea users were more likely to experience new exacerbations than those taking GLP-1 receptor agonists, but there was limited statistical power to detect a significant difference. By contrast, exacerbation rates were similar, regardless of treatment, among people in the normal or overweight BMI categories.
Foer et al conclude that their study demonstrates “an association between GLP-1 [receptor agonist] use and reduced COPD exacerbations.”
They add that the results “also highlight the potential relevance of metabolic pathways in COPD warranting mechanistic and prospective clinical study.”
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Am J Respir Crit Care Med 2023; doi:10.1164/rccm.202303-0491OC