The Role of Fat‐Free Mass in Weight‐Related Complications: A Rapid Review and Meta‐Analysis

Background This review synthesized evidence on the association between fat‐free mass (FFM) metrics and weight‐related metabolic complications in adults with overweight or obesity. Methods A systematic search of Medline, Embase, Web of Science, and Google Scholar (inception to October 2024) identified 32 observational studies involving 138,935 participants. Random‐effects meta‐analyses were conducted for type 2 diabetes (T2DM, 5 studies, n = 41,235), metabolic syndrome (MetS, 3 studies, n = 2832), cardiovascular disease (CVD, 3 studies, n = 8980), and non‐alcoholic fatty liver disease (NAFLD, 3 studies, n = 4570). Heterogeneity was assessed using I 2 . Sensitivity analyses stratification by FFM metric type were performed where feasible. Results Low FFM metrics were significantly associated with increased risk of T2DM (pooled RR = 1.46, 95% CI 1.11–1.91), MetS (OR = 4.48, 95% CI 2.18–9.22), CVD (RR = 2.03, 95% CI 1.27–3.26), and NAFLD (RR = 2.24, 95% CI 1.52–3.32). High heterogeneity was observed for T2DM ( I 2 = 90.9%) and MetS ( I 2 = 79.8%); however, sex‐stratified sensitivity analyses eliminated heterogeneity for T2DM ( I 2 = 0%). Narrative synthesis of remaining studies generally supported these findings, though associations varied according to FFM metric type. Conclusions Low FFM‐related metrics were associated with increased risk of major weight‐related metabolic complications, although the strength and consistency of associations differed by FFM metric type.