Treatment Effects of Liraglutide in Obese Patients With COPD

In obese patients with chronic obstructive pulmonary disease (COPD), liraglutide is efficacious in reducing weight, increasing forced vital capacity (FVC) and carbon monoxide diffusion capacity, and improving COPD Assessment Test (CAT) scores. These findings from a controlled, double-blind trial conducted in Denmark were recently published in the International Journal of Chronic Obstructive Pulmonary Disease.

Liraglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) approved for weight loss and for the treatment of type-2 diabetes mellitus. The drug’s anti-inflammatory effects reduce interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 levels.

Study researchers hypothesized that treatment with liraglutide could improve lung function in patients suffering from obesity and COPD. To test this hypotheses, the researchers selected 40 patients from 2 outpatient clinics, ages 40 to 75 years, who were obese, had COPD, and were former smokers with a 20 or more pack-year history of smoking. The participants were randomized to 2 groups of 20 participants. The groups received a once-daily treatment of liraglutide (3.0 mg, subcutaneously) or placebo subcutaneously for 40 weeks. At baseline and after 4, 20, 40, and 44 weeks, the patients underwent pulmonary-function tests and a 6-minute walking test and took the CAT-score questionnaire.

At week 40, FVC% increased by 7.69% (P =.018), and FVC best measure (FVC_best) went up by 0.33 L in the liraglutide group, compared with levels in the placebo group (P =.007), but the difference in FVC_best and FVC% between groups did not last until week 44. No significant effect of liraglutide was observed on pulmonary function or pulmonary capacity as measured by FEV₁, FEV₁%, or FEV₁/FVC.

At week 40, however FEV₁ was 106 mL higher in the liraglutide cohort than in the placebo group (P =.095). Total lung capacity and residual volume fell significantly by 9.13% (P =.013) and 19.81% (P =.039) respectively, in the liraglutide cohort compared with the placebo cohort at week 44. At week 40, however, no significant difference was evident. Pulmonary diffusion capacity as measured by diffusion capacity for carbon monoxide stayed stable in the liraglutide group until week 40 but dropped over time in the placebo group, resulting in a significant difference of 9.7% between groups at week 40 (P =.012). No significant effect of liraglutide on physical capacity, as measured by the 6-minute walking distance, was seen at week 40 or week 44.

The study limitations included an actual dropout rate larger than anticipated, resulting in the possibility of smaller effect sizes and a higher risk of type-2 statistical errors. Also, a 40-week  treatment period may not be long enough to detect the effects of liraglutide and weight loss, so longer-term studies might be needed to explore the full potential of the drug, according to the researchers.

“GLP-1RAs are not approved for COPD treatment, but our study suggests that liraglutide at 3.0 mg may be an appropriate treatment option in patients with obesity and COPD because it appears to target obesity and pulmonary function,” the authors stated.

Disclosure: Two authors declare affiliations with the pharmaceutical company, Novo Nordisk. The remaining authors declare no competing interests.

Reference

Altintas Dogan AD, Hilberg O, Hess S, Jensen TT, Bladbjerg EM, Juhl CB. Respiratory effects of treatment with a glucagon-like peptide-1 receptor agonist in patients suffering from obesity and chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. Published online February 22, 2022. doi:10.2147/COPD.S350133