SAT-707 Lean Mass Loss after Dietary Weight Loss: A Secondary Analysis of the DIETFITS Randomized Clinical Trial

Abstract Disclosure: S. Kim: None. J. Heo: None. K. Cunanan: None. C. Gardner: None. Background: Increasing concerns have emerged regarding lean mass loss associated with GLP-1-based weight-loss medications. While a certain degree of lean mass loss is expected with any weight-loss intervention, the anticipated and acceptable amounts remain unclear, especially given that existing studies frequently involve small sample sizes (n<50). This study aims to evaluate how the magnitude of weight loss, achieved through dietary modifications without weight-loss medications, influences changes in lean mass. Methods: We conducted a post hoc secondary analysis of the DIETFITS trial (NCT01826591), a randomized study with 609 adults aged 18-50 years and a BMI of 28-40 kg/m². Participants were randomized to either a healthy low-carbohydrate or healthy low-fat diet. We analyzed data from 323 participants (200 females, 123 males) with dual-energy X-ray absorptiometry (DEXA) assessments at baseline and 6 months, stratifying them by weight loss at 6 months: 0-4.9% (n=102), 5-9.9% (n=121), and ≥10% (n=100). The primary outcome is the percentage of lean mass lost relative to total weight loss (%LML), calculated by dividing the change in lean mass from baseline to 6 months by the change in total mass over the same period. We also evaluated fat-to-lean mass (FLM) ratio, calculated as the ratio of fat mass to lean mass. Results: At baseline, the three weight-loss groups had similar mean (±SD) weight (94.8±14.7kg), waist circumference (105.9±11.3cm), body mass index (33.1±3.4kg/m2) and percentage of lean mass relative to total mass on DEXA (60.7±6.6%). At 6 months, mean weight loss was -2.7±1.3 kg, -6.8±1.7 kg, and -14.0±4.2 kg for the groups losing 0-4.9%, 5-9.9%, and ≥10% of their baseline weight, respectively. A larger mean lean mass loss was observed for groups with greater weight loss (-0.6±1.4 kg, -1.9±1.2 kg, -3.8±1.9 kg, p<0.001). However, distributional spread appears similar across groups (median %LML [interquartile range]: 24% [-12, 54], 30% [21, 39], 29% [21,35], in those losing 0-4.9%, 5-9.9%, and ≥10%, respectively). Notably, %LML varied widely when weight loss was less than 5% and quickly reached a plateau for weight loss. Men lost greater %LML than women when weight loss was ≥5% (33% [24, 41] vs 28% [17, 36], p=0.001). FLM ratio significantly decreased in both genders. In those that lost ≥10% of baseline weight, mean FLM decreased from 0.72±0.12 to 0.57±0.12 in women and 0.45±0.08 to 0.33±0.08 in men. Conclusions: Our findings establish a benchmark for evaluating %LML after weight-loss interventions and suggest that the proportion of lean mass loss is consistent regardless of the total weight lost when achieved through dietary modifications. Presentation: Saturday, July 12, 2025