Effects of Incretin‐Based Therapies, Diet and Exercise Interventions, and Bariatric Surgery on Fat‐Free Mass in Adults With Overweight or Obesity: A Systematic Review and Meta‐Analysis

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BACKGROUND: Maintaining fat-free mass (FFM) during weight loss is important to maintain a healthy body composition. This review examined changes in FFM during weight loss induced by diet and exercise interventions, incretin-based therapies, and bariatric surgery, and assessed whether the relative loss of FFM differs by weight-loss modality. METHODS: A systematic search of PubMed, Cochrane Library, and Embase was conducted for randomised controlled trials published from 2015 to October 21st, 2025. Eligible studies included adults with overweight or obesity (with or without type 2 diabetes), achieving ≥ 10% weight loss of total body weight through diet and exercise, incretin-based, or surgical interventions. The studies were required to report measurements of either FFM using dual-energy X-ray absorptiometry or muscle mass using computed tomography or magnetic resonance imaging. RESULTS: Twelve diet and exercise, five incretin-based therapy, and four bariatric surgical studies (1334 participants) were included. The pooled changes in FFM were -1.8 kg (95% CI: -2.6, -1.0) for diet and exercise interventions, -4.8 kg (95% CI: -5.6, -3.9) for incretin-based therapies versus placebo, and -9.1 kg (95% CI: -12.3, -6.0) for bariatric surgery. The proportion of total weight loss attributable to FFM was 14.9% for diet with/without exercise interventions (22.3% for diet without exercise and 7.7% for diet with exercise), 33.3% for incretin-based therapies, and 34.2% for surgical interventions. CONCLUSION: Among the included studies with ≥ 10% weight loss in individuals with overweight or obesity, diet and exercise interventions were associated with the smallest reductions in FFM, whereas incretin-based therapies and bariatric surgery showed substantially greater losses. Given the importance of FFM, strategies to preserve FFM, particularly exercise, should be included in all weight-loss approaches.

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