Introduction: Low fat-free mass (FFM) is linked to poor health outcomes in COPD, including impaired exercise tolerance and premature death.

Aim: To synthesise evidence on the effectiveness of interventions targeting FFM in people with COPD.

Methods: Searches of electronic databases (MEDLINE, Web of Science, EMBASE) and trial registers (ClinicalTrials.gov) were undertaken from inception to August 2022 for randomised studies of interventions assessing measures of FFM in COPD. The primary outcome was change in FFM (including derivatives).

Results: 99 studies (n=5,138 people with COPD) of 11 intervention components, used alone or in combination, were included. Exercise training increased mid-thigh cross-sectional area measures (k=3, standardised mean difference (SMD)=1.04, 95% confidence interval [CI] 0.02-2.06, p=0.04), but not FFM (k=4, SMD=0.03, 95% CI -0.18-0.24, p=0.75). Nutritional supplementation increased FFM index (k=11, SMD=0.31, 95% CI 0.13-0.50, p<0.001), but not FFM (k=19, SMD=0.16, 95% CI -0.06-0.39, p=0.16). Combined, exercise training and nutritional supplementation increased measures related to FFM in 67% of studies. Anabolic steroids increased FFM (k=4, SMD=0.98, 95% CI 0.24-1.72, p=0.009). Neuromuscular electrical stimulation increased measures related to FFM in 50% of studies.

Conclusions: Exercise training and nutritional supplementation are not effective in isolation to induce increases in FFM but are for localised muscle and index measures. Combined, exercise and nutritional supplementation shows promise as a strategy to increase FFM in COPD. Anabolic steroids are efficacious for increasing FFM in COPD.