OBJECTIVES: To estimate the efficacy and safety of glycopirronium-indacaterol (GLN/IND) as maintenance therapy for moderate to severe chronic obstructive pulmonary disease (COPD) compared to other first-line treatments, through a systematic review and meta-analysis. METHODS: A detailed search was performed in eight electronic databases (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects (DARE), LILACS, Cochrane Central Register of Randomized Controlled Trials, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov) searching for clinical trials that compared efficacy and/or safety of glycopirronium (GLN) alone or GLN/IND as first-line drugs for moderate to severe COPD. Seven functional and quality of life outcomes were collected. An expert panel supported and validated the methodology. Finally, a meta-analysis was performed when the homogeneity of the information permitted. RESULTS: CONCLUSIONS: We conclude that GLN/IND is more effective than other first-line drugs in the management of moderate to severe COPD, with a similar safety profile.