GLP-1 receptor agonists have been linked to a lower risk of severe COPD exacerbations in people with co-existing type 2 diabetes, suggesting a potential role for novel antihyperglycaemics in obstructive lung disease.
In a large population based study GLP-1 receptor agonists were associated with a 30% decreased risk of severe exacerbation (3.5 v 5.0 events per 100 person years) compared to sulfonylureas. However DPP-4 inhibitors were not consistently associated with an overall lower risk of exacerbations, and SGLT-2 inhibitors were associated with a reduced risk of severe, but not moderate, exacerbations.
Writing in the BMJ the Canadian team of researchers noted that in addition to cardiovascular benefits, emerging evidence suggested that novel antihyperglycaemic agents may also have beneficial effects on lung function.
For example, in murine models of obstructive lung disease direct stimulation of the GLP-1 receptors reduced airway hyperresponsiveness and inflammation. GLP-1 receptor agonists had also been shown to improve forced vital capacity among patients with compromised lung function in randomised controlled trials.
To investigate the association further the researchers used data from three UK cohorts: 1,252 patients with COPD and type 2 diabetes starting GLP-1 receptor agonists and 14,259 starting sulfonylureas; 8,731 patients starting DPP-4 inhibitors and 18 204 starting sulfonylureas; and 2,956 patients starting SGLT-2 inhibitors and 10, 841 starting sulfonylureas.
“We chose sulfonylureas as the active comparator as they are used at a similar disease stage as incretin based drugs and SGLT-2 inhibitors, continue to be widely prescribed worldwide and have not been previously associated with an increased incidence of exacerbation of chronic obstructive pulmonary disease,” they explained.
Results showed that GLP-1 receptor agonists were associated with a 30% decreased risk of severe exacerbation (3.5 v 5.0 events per 100 person years; hazard ratio 0.70, 95% confidence interval 0.49 to 0.99) and moderate exacerbation (0.63, 0.43 to 0.94).
In contrast, DPP-4 inhibitors were associated with a modestly decreased incidence of severe exacerbation (4.6 v. 5.1 events per 100 person years; hazard ratio 0.91, 0.82 to 1.02) and moderate exacerbation (0.93, 0.82 to 1.07), with confidence intervals including the null value.
SGLT-2 inhibitors were associated with a 38% decreased risk of severe exacerbation (2.4 v 3.9 events per 100 person years; hazard ratio 0.62, 0.48 to 0.81) but not moderate exacerbation (1.02, 0.83 to 1.27).
Overall, the findings remained robust in several sensitivity analyses, the researchers said.
According to the authors, there were several biological mechanisms that could explain their results, such as the systemic anti-inflammatory effects of GLP-1 receptor agonists and their link to significant weight loss.
However, the study also had limitations including the potential for misclassification, a lack of data on medication adherence and residual confounding.
“Further research, including confirmatory randomised 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 type 2 diabetes and chronic obstructive pulmonary disease,” the researchers concluded.