A new systematic review and meta-analysis of studies presented at this year's European Congress on Obesity in Istanbul, Turkey (12-15 May) shows that diet and exercise interventions result in a lower proportion of fat-free mass loss compared with obesity surgery or obesity drugs among people undergoing a weight loss of 10% or more. The study is by Professor Signe Torekov and Lærke Bruun Madsen, PhD student at the University of Copenhagen, Denmark, and colleagues.
Traditionally, weight reduction relied on behavioral interventions, and for eligible patients, obesity surgery. However, diet and exercise interventions require sustained adherence and substantial behavioral changes, while obesity surgery remains highly invasive. Recent advances in incretin-based drugs for obesity have changed obesity care because of substantial weight loss. Despite their efficacy, concerns have emerged regarding potential loss of fat-free mass, including loss of muscle and bone. Preserving fat-free mass during weight loss is critical, as muscle and organ tissues exhibit a higher metabolic rate than fat mass, supporting metabolism and enabling sustained weight loss. Loss of fat-free mass, particularly muscle and bone mass, can impair physical function and metabolic health.
This systematic review examined the absolute and relative changes in fat-free mass in people experiencing 10% or higher weight loss induced by diet and exercise interventions, incretin-based obesity drugs, or obesity surgery, and assessed whether the relative loss of fat-free mass differs by weight-loss modality.
Randomised controlled trials published between 2015 and October 21, 2025, were identified through searches of PubMed, Embase, and the Cochrane Library. Eligible studies included adults with overweight or obesity, with or without type 2 diabetes, who had achieved a weight loss of at least 10% through diet and exercise interventions, incretin-based obesity drug interventions, or obesity surgery interventions. The studies had to report accurate measurements of either fat-free mass using dual-energy X-ray absorptiometry or muscle mass using computed tomography (CT) or magnetic resonance imaging (MRI). Mean changes in fat-free mass and the proportion of weight loss attributable to fat-free mass were then calculated.
A total of 21 studies comprising 1,334 participants were included (12 diet and exercise studies, 5 obesity drug studies and 4 obesity surgery studies). The mean changes in fat-free mass were -1,80 kg for diet and exercise interventions, -4.75 kg for incretin-based obesity drug therapies versus placebo, and -9.14 kg for obesity surgery interventions; the authors also calculated the pooled mean weight loss for all three interventions: diet and exercise -11.6 kg; incretin based obesity drug therapies versus placebo -15.9 kg; and obesity surgery interventions -27.4 kg.
The proportion of total weight loss attributable to fat-free mass was 14,3% for diet and exercise interventions, 31.5% for incretin-based obesity drug therapies versus placebo, and 32.9% for obesity surgery interventions. Muscle mass specifically was only measured using magnetic resonance imaging MRI in one study, thus making a specific analysis of muscle mass alone (instead of fat-free mass) not feasible.
The authors say: "Among the included studies with at least 10% weight loss in individuals with overweight or obesity, diet and exercise interventions were associated with the smallest reductions in fat-free mass, whereas incretin-based obesity drugs and obesity surgery were associated with substantially greater proportional losses of fat-free mass. These findings underscore the importance of incorporating strategies aimed at preserving fat-free mass, particularly structured exercise across all weight-loss approaches."
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