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Life sciences · Review
Nutrition and Health · September 17, 2026
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Background The increasing global burden of obesity and type 2 diabetes mellitus (T2DM) poses a major public health challenge. Nutrigenomics has emerged as a promising approach for managing these metabolic diseases through specific gene–diet interactions. Aim This systematic review aimed to synthesize evidence on the effects of nutrigenomics in the prevention and management of obesity and T2DM in human populations. Methods An extensive search was performed across four databases from inception to June 2025. Eligibility criteria were: randomized controlled trials (RCTs), participants with obesity (body mass index (BMI): 25–40 kg/m 2 ), prediabetes, and/or diagnosed with T2DM, nutrigenomics-based dietary intervention studies, and reporting obesity or diabetes management as the primary outcome. Risk of bias (RoB) was assessed using the RoB visualization tool. Narrative evidence synthesis was done owing to heterogeneity in study populations, genotypes, diet-gene associations, and outcome measures. Summary Of 1278 articles screened, six RCTs met the eligibility criteria. The included studies demonstrated that nutrigenomics-based dietary interventions and related molecular responses may influence obesity and T2DM-related outcomes. Specific genetic variants, including APOA2, Melatonin receptor 1B ( MTNR1B), Circadian locomotor output cycles kaput ( CLOCK), and PP2C domain-containing protein phosphatase 1K ( PPM1K), as well as molecular response markers such as RIPK3 and RNF216, were associated with changes in weight, BMI, waist circumference, and insulin sensitivity following dietary interventions. RoB analysis revealed that only one study (16.7%) demonstrated low RoB. The findings suggest a potential role for nutrigenomics in the prevention and management of obesity and T2DM; however, more robust and standardized RCTs are needed.