Background <p>Gene-based nutrition recommendations have emerged as a strategy for weight management, but evidence of their added value over standard advice remains inconclusive. This randomized controlled trial evaluated the effects of MyGeneMyDiet^®, a genotype-informed lifestyle program, compared with standard recommendations on anthropometric, biochemical, and dietary outcomes in Filipino adults with overweight and obesity over 12 months.</p> Methods <p>In this randomized controlled trial, participants received either MyGeneMyDiet^® or standard recommendation (control). Both groups underwent regular nutrition counseling during the active phase (months 0–6) before transitioning to an inactive phase (free-living conditions, months 6–12). Primary outcomes included weight, BMI, waist circumference, and body fat percentage; secondary outcomes were dietary intake and biochemical markers. Analyses were conducted according to randomized group assignment. Primary analyses used available case-data at each timepoint, with paired t-tests for within-group comparisons and ANCOVA for between-group differences. Sensitivity analyses used Last Observation Carried Forward (LOCF) and Inverse Probability of Attrition Weighting (IPAW) to address loss-to-follow-up.</p> Results <p>Of the 136 screened, 52 initiated the intervention (MyGeneMyDiet^®, <i>n</i> = 29; standard recommendation, <i>n</i> = 23), and 27 completed the 12-month follow-up (MyGeneMyDiet^®, <i>n</i> = 15; standard recommendation, <i>n</i> = 12). Both groups lost weight over 12 months, with no evidence of meaningful between-group differences. During the 6-month active phase, baseline-adjusted analyses showed no significant between-group differences in weight (-0.36&#xa0;kg [95% CI: -1.77, 1.04]), BMI (0.11&#xa0;kg/m² [95% CI: -0.51, 0.73]), waist circumference (-0.27&#xa0;cm [95% CI: -2.23, 1.69]), or body fat percentage (0.92% [95% CI: -0.86, 1.05]). These trends persisted through 12 months. Both groups reported reductions in energy intake; within-group decreases in energy and macronutrients were observed in the MyGeneMyDiet^® arm at month 12, but these did not translate into superior anthropometric or metabolic outcomes.</p> Conclusions <p>We found no evidence of meaningful differences between gene-based and standard recommendations in anthropometric or metabolic outcomes over 12 months. While genotype-informed counseling was associated with reported reductions in dietary intake at some timepoints, these changes did not translate into superior clinical outcomes. These findings suggest that genetic tailoring alone may not enhance long-term weight management beyond standard counseling but offer insight into the feasibility of integrating gene-based recommendations in low- and middle-income country settings.</p> Clinical Trial registration <p>clinicaltrials.gov, NCT05098899 (<a href="https://clinicaltrials.gov/study/NCT05098899">https://clinicaltrials.gov/study/NCT05098899</a>); registered 20 October 2021.</p>