Nutrigenetic Tailored Diet Results in Long-Term (12 Months) Weight-Loss Compliance and Improved Cardiometabolic Outcomes in a Real-World Community-Based Setting

Background/Objectives: Individual responses to weight-loss diets vary widely due to genetic, metabolic, and lifestyle factors, motivating individualized approaches over “one-size-fits-all” advice. We aimed to evaluate long-term (12-month) weight loss, weight maintenance, and cardiometabolic outcomes of a cohort following a nutrigenetically tailored Mediterranean-style dietary program in a real-world, community setting. Methods: The retrospective data cohort included 426 Israeli adults (mean BMI 32.11 ± 4.58 kg/m2; 66.9% women) who participated in a nutrigenetic weight-loss program. Following nutrigenetic direct-to-consumer screening of 425 genetic variants, the participants received a 3-month personalized adjusted diet with remote dietitian-led follow-up by telephone, after which they transitioned to a 9-month self-monitoring and maintenance period. Blood biochemical parameters were reported from routine Health Maintenance Organization (HMO) laboratory testing. Weight/BMI trajectories (0–3, 3–6, 6–9, 9–12 months) were evaluated using linear mixed-effects models; biomarker changes were analyzed with repeated-measures MANOVA and follow-up univariate ANOVAs. Results: Model-estimated cumulative weight loss at 12 months was 10.12 kg (11.4% of baseline) with a mean BMI reduction of 3.68 kg/m2 (p < 0.001). The steepest decline occurred during months 3–6 (−1.13 kg/month). Triglycerides (−14.06 mg/dL), total cholesterol (−4.68 mg/dL), LDL cholesterol (−2.49 mg/dL), fasting glucose (−5.14 mg/dL), and HbA1c (−0.14%) improved significantly (p < 0.05), while HDL cholesterol levels remained stable (+0.86 mg/dL; p > 0.05) at 12 months. Among participants with elevated baseline biochemical values, levels transitioned to normal range by 12-month follow-up for triglycerides (46.4%), total cholesterol (29.4%), LDL cholesterol (34.5%), glucose (39.6%), and HbA1c (35.5%). Conclusions: In a real-world cohort, inclusion of genetic information to personalize dietary guidance was implemented through a flexible, individually tailored program supported by an initial 3-month phase of remote dietitian-led counseling. This approach was associated with durable, clinically meaningful reductions in weight and cardiometabolic risk markers over 12 months. Randomized trials are warranted to confirm causality and evaluate cost-effectiveness.