Effect of fixed-dose tiotropium/olodaterol combined therapy on exercise-related outcome measures in individuals with chronic obstructive pulmonary disease: a systematic review and meta-analysis

This systematic review aimed to summarize the evidence on the effect of the fixed-dose combination of tiotropium/olodaterol (Tio/Olo 5/5 μg FDC) on exercise-related outcome measures. We included randomized clinical trials (RCTs) from four databases that investigated the effectiveness of Tio/Olo 5/5 μg FDC on exercise tolerance, breathlessness, lung function, and physical activity from inception to October 2024. Findings from eight RCTs indicated that Tio/Olo 5/5 μg FDC was superior to Tio 5 μg or placebo for the following outcomes: exercise tolerance [Tio 5 μg: 3 RCTs, mean difference (MD) = 16.6 m, 95% CI: 5.2–28.1, <i>p</i> &lt; 0.001], exercise endurance time [Placebo: 2 RCTs, SMD = 0.29, 95% CI: 0.19–0.39, <i>p</i> = <i>p</i> &lt; 0.001], inspiratory capacity [Tio 5 μg: 3 RCTs, MD = 0.13 L, 95% CI: 0.07–0.19, <i>p</i> &lt; 0.001], and forced expiratory volume in 1 second (FEV₁) [Tio 5 μg: 4 RCTs, MD = 0.12 L, 95% CI: 0.11–0.14, <i>p</i> &lt; 0.001; Placebo: 2 RCTs, MD = 0.33 L, 95% CI: 0.3–0.35, <i>p</i> &lt; 0.001], with no effect on physical activity levels. Tio/Olo 5/5 μg FDC compared to Tio 5 μg or placebo may improve exercise tolerance and lung function, but not physical activity levels in COPD. The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): number CRD42024598553.