A Review on the Safety of Two Single-Inhaler Triple Therapy Regimens: Fluticasone/Umeclidinium/Vilanterol versus Formoterol/Budesonide/Glycopyrronium

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disorder of the airway characterized by persistent airflow limitation, recurrent exacerbations, and substantial morbidity and mortality worldwide. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommend escalating to triple inhaler therapy for patients who continue to experience symptoms and frequent exacerbations despite dual bronchodilator therapy. Single inhaler triple therapy (SITT) improves adherence, reduces exacerbations, and simplifies treatment regimens compared with multiple inhaler use.Two major SITT combinations widely used in COPD management are fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) and budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/FOR). FF/UMEC/VI combines an inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA), and long-acting β2-agonist (LABA) delivered once daily, whereas BUD/GLY/FOR provides similar pharmacological classes in a twice-daily regimen.The IMPACT trial demonstrated that FF/UMEC/VI significantly decrease the risk of moderate to severe exacerbations compared with dual therapy with a higher incidence of pneumonia. Similarly, the ETHOS trial showed that BUD/GLY/FOR reduced exacerbations and all-cause mortality while maintaining an acceptable safety profile. However, safety concerns persist regarding the risk of pneumonia, cardiovascular events, oral candidiasis, osteoporosis, hyperglycemia, glaucoma, urinary retention, and treatment discontinuation.This review aims to compare the safety profiles of FF/UMEC/VI and BUD/GLY/FOR evidence obtained from randomized controlled trials, meta-analyses, and real-world studies to support rational COPD treatment selection.