GLP-1 receptor agonists halt COPD exacerbations in T2D patients

Use of glucagon-like peptide 1 (GLP-1) receptor agonists or sodium-glucose co-transporter-2 (SGLT-2) inhibitors, compared with sulfonylureas, helps prevent severe exacerbations of chronic obstructive pulmonary disease (COPD) in patients with type 2 diabetes (T2D), a UK study has shown.

On the other hand, the association of dipeptidyl peptidase 4 (DPP-4) inhibitors with a reduced risk of COPD exacerbations is uncertain.

This population-based study had three active comparators. The first cohort included 1,252 patients initiating GLP-1 receptor agonists and 14,259 sulfonylureas. The second cohort included 8,731 patients on DPP-4 inhibitors and 18,204 sulfonylureas. Finally, the remaining cohort included 2,956 patients starting SGLT-2 inhibitors and 10,841 sulfonylureas.

The researchers fitted Cox proportional hazards models with propensity score fine stratification to estimate hazard ratios (HRs) and 95 percent confidence intervals (CIs) of severe exacerbation of COPD, defined as hospital admission, separately for GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors.

In addition, they determined whether these drugs were associated with a reduced risk of moderate exacerbation, defined as a coprescription of an oral corticosteroid and an antibiotic along with an outpatient diagnosis of acute COPD exacerbation on the same day.

GLP-1 receptor agonists, compared with sulfonylureas, resulted in a 30-percent reduced risk of severe (3.5 vs 5.0 events per 100 person-years; HR, 0.70, 95 percent CI, 0.49‒0.99) and moderate exacerbations (HR, 0.63, 95 percent CI, 0.43‒0.94). [BMJ 2022;379:e071380]

SGLT-2 inhibitors also led to a decreased risk of severe exacerbations (2.4 vs 3.9 events per 100 person-years; HR, 0.62, 95 percent CI, 0.48‒0.81), but not moderate exacerbations (HR, 1.02, 95 percent CI, 0.83‒1.27).

Finally, DPP-4 inhibitors correlated with a modest and nominal reduction in the incidence of severe (4.6 vs 5.1 events per 100 person-years; HR, 0.91, 95 percent CI, 0.82‒1.02) and moderate exacerbations (HR, 0.93, 95 percent CI, 0.82‒1.07), with CIs including the null value.

“Several potential mechanisms may explain the decreased risk of COPD exacerbation observed with GLP-1 receptor agonists,” the researchers said.

Firstly, previous studies have shown that GLP-1 receptor agonists reduce local inflammation and airway hyper-responsiveness in murine models, in isolated human airways, and among patients with T2D and COPD. [Am J Respir Cell Mol Biol 2016;55:804-814; Endocrinology 2013;154:4503-4511; Int J Mol Sci 2015;16:20195-20211; Expert Rev Clin Immunol 2021;17:1053-1057; Respir Med 2019;154:86-92]

Secondly, COPD is thought to be the respiratory manifestation of a chronic systemic inflammation, which is caused by underlying risk factors such as obesity, hypertension, and smoking. [Mediators Inflamm 2016;2016:3094642]

Thirdly, abdominal obesity reduces the lung capacity by pushing the diaphragm against the thorax, thereby increasing the risk of COPD exacerbations. GLP-1 receptor agonists help reduce weight, which then leads to decreased COPD exacerbations. [Ann Am Thorac Soc 2018;15:184-191; BMJ 2021;372:m4573; Diabetes Care 2021;44(Suppl 1):S111-124]

“Further research, including confirmatory randomized controlled trials, will be needed to investigate the potential of GLP-1 receptor agonists and SGLT-2 inhibitors as a therapeutic option in patients with T2D and COPD,” the researchers said.