Researchers Probe Effect of Diabetes Drugs on COPD Exacerbations

A recent study found that patients with both chronic obstructive pulmonary disease (COPD) and diabetes using oral hypoglycemic agents had lower risks of severe exacerbations than controls.

According to a recent study, researchers found that patients with chronic obstructive pulmonary disease (COPD) using certain antidiabetic medications had lower risks of experiencing severe exacerbations.

The authors, writing in Respiratory Research, noted that patients with COPD often have comorbid conditions, including diabetes, which can make symptoms worse and increase the risk of exacerbations

The authors said that preclinical data has indicated that some diabetes drugs may have anti-inflammatory effects on COPD, but that real-world evidence is lacking. To assess the association between use of various types of oral hypoglycemic agents (OHAs) and the risk of severe COPD exacerbations in patients with both diseases, they analyzed 23,875 patients with COPD receiving at least 1 OHA for diabetes entered in the Taiwan National Health Insurance claims database between January 1, 2000, and December 31, 2015.

The disease risk score-matched nested case-control study was analyzed with conditional logistic regression to estimate odds ratios (OR) of severe COPD exacerbation for each type of OHAs.

Cases of severe COPD exacerbations were defined as patients who were hospitalized with a primary diagnosis of COPD or who who had a first hospital admission for acute respiratory failure and COPD as a primary and secondary cause, respectively, during follow-up.

Each case was matched to 4 randomly-selected controls by cohort entry date, disease risk score (DRS), and COPD medication regimens using the incidence density sampling approach.

After DRS matching, researchers included 2700 cases and 9272 controls; nearly 60% were men, with a mean age of 69.1 years,

Use of metformin versus other OHAs was linked with a 15% (adjusted OR [aOR], 0.85; 95% CI, 0.75–0.95) reduced risk of severe COPD exacerbation.

How long a patient took the OHA also had a positive effect on reducing exacerbations.

Taking metformin for 91–180 and 181–365 days was associated with a 28% (aOR, 0.72; 95% CI, 0.58–0.89) and 37% (aOR, 0.63; 95% CI 0.51–0.77) lower risk of severe COPD exacerbation, respectively.

In addition, the reduced risk persisted in patients who had undergone spirometry testing and had no previous severe COPD exacerbation or heart failure.

Similarly, 91–180 days of sulfonylureas therapy led to a 28% (aOR, 0.72; 95% CI,0.58–0.90) lower risk, and longer treatments consistently yielded 24–30% lower risks.

Use of thiazolidinediones for more than 181 days yielded an approximately 40% decreased risk.

The authors said it was the first such study to show that some OHAs reduce the risk of COPD exacerbations in patients with both COPD and diabetes.

The suggested several possible reasons for the observed effect with metformin, including that the drug has an anti-inflammatory effect by activating adenosine monophosphate-activated protein kinase as well as other inflammatory markers; that it could improve respiratory muscle function and keep COPD symptoms from worsening; and that it may mitigate insulin resistance, which is linked to the chronic inflammation seen in COPD.

The reduced risk seen with sulfonylureas may possibly stem from their effect on hypoxia-induced insulin resistance.

“Our evidence on the reduction in the risk of severe COPD exacerbation following treatment with specific types of OHAs should be incorporated into the benefit-and-risk evaluation of pharmacological treatments for management of [diabetes] in patients with COPD,” wrote the investigators.


Wang, MT, Lai, JH, Huang YL, et al. Use of antidiabetic medications and risk of chronic obstructive pulmonary disease exacerbation requiring hospitalization: a disease risk score-matched nested case–control study. Respir Res. Published online December 2, 2020. oi: 10.1186/s12931-020-01547-1