GLP-1 receptor agonists and SGLT-2 inhibitors reduce COPD exacerbations among diabetes patients

Canada: A recent study published in the BMJ has highlighted that glucagon-like peptide 1 (GLP-1) receptor agonists, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors are tied to lower risk of Chronic Obstructive Pulmonary Disease (COPD) exacerbation in those patients who have COPD and Type 2 Diabetes. The researchers also added that dipeptidyl peptidase 4 (DPP-4) inhibitors have no clear association in reducing COPD exacerbations.

GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 are commonly used antihyperglycemic. Previous studies have reported their favourable cardiovascular effects. Adding data further, emerging data suggest that these have benefits on lung functions, too, especially among COPD patients.

GLP-1 receptor agonists may improve forced vital capacity in cases of compromised lung function. DPP-4 inhibitors reduce bronchial hyperresponsiveness and increase endogenous GLP-1 concentration. SGLT-2 receptors though not expressed in the lungs but induce glucosuria and reduce pneumonia risk.

The data on the action of antihyperglycaemic on exacerbations in respiratory disease remains limited. The data suggest that DPP-4 inhibitors do not decrease COPD exacerbations, while GLP-1 receptor agonists decrease it by 48% in type 2 diabetes and COPD/asthma. But these studies have not considered other clinically important outcomes.

Against the above background, a study was conducted in the Department of Epidemiology at McGill University, Montreal, QC, Canada, by Richeek Pradhan, a doctoral student. This was a team of researchers, and the co-researcher was Sally Lu.

The key points of the study are:

• The study design was a population-based cohort study.

• Data was from UK national, primary and secondary care datasets.

• The first comparison (first cohort) was between GLP-1 receptor agonists (1252 patients) vs sulfonylureas (14259 patients).

• The second comparison (second cohort) was between DPP-4 inhibitors (8731 patients) vs sulfonylureas (18204 patients).

• The third comparison (third cohort) was between SGLT-2 inhibitors (2956 patients) vs sulfonylureas (10841 patients).

• In the first cohort, patients had a mean age of 66 years with 55 % men and FEV1 ≤ 80% was 61 %.

• In the second cohort, the mean age of patients was 69 years, and 56 % were men. The FEV1 ≤80 % is 61 %.

• In the third cohort, the mean age of patients was 68 years, with 57 % men and FEV1 ≤ 80% was 62%.

• Cox proportional hazards models estimated hazard ratios (HR) and 95% CI of severe exacerbation of COPD separately for the three categories.

• The comparison was made with sulfonylureas.

• GLP-1 receptor agonists decreased 30 % of the risk of COPD severe and moderate exacerbation with HR of 0.70 and 0.63, respectively.

• DPP-4 inhibitors modestly decreased the incidence of exacerbation. The HR for severe and moderate exacerbation was 0.91 and 0.93, respectively. (confidence intervals included the null value).

• SGLT-2 inhibitors were tied to a 38% decreased risk of severe exacerbation with HR 0.62. These were not related to a decrease in moderate exacerbation with HR 1.02

The researchers wrote, "To our knowledge, no real-world study has assessed whether SGLT-2 inhibitors decrease the risk of COPD exacerbations. Since type 2 diabetes patients are at high risk of COPD, we aimed to determine if GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors, separately, reduce COPD exacerbation in such cases or not, compared with sulfonylureas."

They said, "We observed a 32% lower incidence of COPD exacerbation during the first year of follow-up (HR 0.68). All three available SGLT-2 inhibitors reduced the risk of severe exacerbations."

While discussing, they mentioned, "Our findings indicate that GLP-1 receptor agonists cause 30% and 37 % lower risk of severe and moderate exacerbation than sulfonylureas. Our study results are in line with recent US IBM MarketScan Commercial Claims Database."

Our study followed patients for up to 14 years, they wrote.

Further reading:

Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study BMJ 2022; 379.