Our meta-analysis, encompassing 30 studies with 46,976 subjects, aimed to explore the impact of fat mass and obesity-associated protein (FTO) genotypes on weight response to exercise and dietary interventions in overweight and obese adults. Electronic databases including PubMed and Google Scholar were searched from 2020 to September 2023 to identify relevant studies. Results revealed a significant reduction in body weight among individuals with the FTO risk allele following exercise and diet interventions (standardized mean difference [SMD] = − 0.619, 95% CI: − 1.137, − 0.100; p = .01). When examining FTO variants, both AA (SMD = − 0.148, 95% CI: − 0.282, − 0.014, p = .03, I2 = 24.96) and TA genotypes (SMD = − 0.674, 95% CI: − 1.162, − 0.186, p = .007, I2 = 91.12) showed significant weight reduction compared to the TT genotype. Moreover, individuals with the high-risk genotype AA + TT achieved greater weight loss compared to those with the normal-risk genotype TT (SMD = − 0.419, 95% CI: − 0.655, −0.183, p = .0001, I2 = 92.08) in the dominant genetic model. Subgroup analysis indicated that FTO risk allele carriers (AA + AT) with exercise interventions lasting six months and a body mass index of 25 – 29 experienced greater weight loss compared to TT carriers. These findings emphasize the importance of genetic considerations in weight management interventions and suggest personalized approaches for combating obesity. Further clinical trials are warranted to validate our study’s findings.
