The Effect of Metabolic Syndrome Status on Lung Function and Patient-reported Outcomes in Patients with COPD Receiving Nebulized Glycopyrrolate

Background: Concurrent chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) represent an important clinical phenotype with overlapping symptomology. The effect of MetS in COPD patients was assessed following treatment with nebulized glycopyrrolate (GLY; administered via eFlow (R) Closed System Nebulizer). Methods: Posthoc analyses were performed on pooled lung function, patient-reported outcome (PRO) and safety data by MetS status from patients treated with placebo, GLY 25 and 50 mcg twice daily in two 12-week studies (GOLDEN 3 and 4; N=1293). Patients with MetS were characterized as having >= 3 of hypertension, hyperlipidemia, diabetes, body mass index (BMI) > 30 kg/m(2) risk factors. The results are presented for the Food and Drug Administration-approved GLY 25 mcg dose. Results: A total of 25% of patients met MetS criteria. At baseline, the MetS subgroup had higher BMIs, more ex smokers, greater incidences of cardiovascular risk factors, and MetS-specific risk factors were 2-14 times higher than non-MetS. At 12 weeks, GLY produced significant, clinically important improvements (MetS: 0.121 L; non-MetS: 0.083 L) in trough forced expiratory volume in 1 second. In the non-MetS group, significant improvements occurred in the St George's Respiratory Questionnaire (MetS: -2.28, p=0.157; non-MetS: -3.71) and Evaluating Respiratory Symptoms in COPD tool (MetS: 0.42, p=0.574; non-MetS: -1.61) total scores. Incidence of adverse events was similar with GLY versus placebo regardless of MetS status. Conclusions: GLY was well-tolerated and significantly improved lung function regardless of MetS status, while significant PRO improvements occurred in non-MetS patients. These results highlight the importance of comorbidities on bronchodilator responses and patient symptoms in COPD patients.