Genetic and Behavioral Predictors of Long-Term Weight Loss Maintenance: A Systematic Review of Evidence From Observational and Genetic Studies.

BACKGROUND

Long-term weight loss maintenance remains a significant challenge in obesity management, despite advances in behavioral, dietary, and medical interventions. The objective of this study is to identify consistent genetic and behavioral predictors associated with sustained weight loss in adults with overweight or obesity.

METHODS

We searched PubMed, Embase, PsycINFO, Web of Science, and Google Scholar for peer-reviewed studies published from January 2010 to April 2025. Eligible studies included observational and genetic investigations involving adults who maintained at least 10% weight loss for one year or more. Quality was assessed using the Newcastle-Ottawa Scale (NOS) and genetic validity criteria. A thematic synthesis categorized predictors as behavioral or genetic.

RESULTS

24 studies met the inclusion criteria (15 observational, nine genetic). Consistent behavioral predictors included increased physical activity, dietary restraint, low disinhibition, and improved psychological health. Genetically, FTO risk alleles and higher polygenic risk scores were associated with weight regain; however, structured behavioral interventions mitigated this effect. Specific gene variants (e.g., PPARγ, TIMP4) were linked to enhanced weight loss outcomes in response to multidisciplinary interventions.

CONCLUSION

Both genetic and behavioral factors independently and interactively influence long-term weight loss maintenance. Integrating genetic risk profiling with personalized behavioral strategies may improve obesity treatment outcomes.