The integration of precision nutrition with pharmacological therapies has been proposed as a strategy to optimize therapeutic efficacy, tolerability, and patient-centered outcomes in chronic metabolic diseases. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have substantially advanced the treatment of obesity and type 2 diabetes mellitus by promoting substantial weight loss and improving glycemic control and cardiometabolic risk profiles. However, significant interindividual variability in therapeutic response, frequent gastrointestinal adverse events leading to treatment discontinuation, and the potential loss of lean body mass remain major clinical challenges that limit real-world therapeutic efficiency. Emerging evidence suggests that nutritional status, dietary patterns, body composition, inflammatory burden, and gut microbiota composition may influence both the efficacy and tolerability of GLP-1-based therapies. This review explores the role of precision nutrition as an adjunctive strategy to support GLP-1 RA treatment outcomes through personalized dietary interventions and targeted nutritional support. Particular attention is given to protein intake optimization for lean mass preservation, micronutrient adequacy, microbiota modulation, anti-inflammatory dietary approaches, and the management of gastrointestinal symptoms. Furthermore, the review explores the emerging contribution of nutrigenomics, metabolomics, microbiome-based stratification, digital health technologies, and artificial intelligence in advancing pharmacometabolic personalization. The potential pharmacoeconomic implications of integrated nutritional-pharmacological strategies are discussed, including the potential for improved adherence to reduce treatment-related costs, prevent complications, and enhance long-term metabolic sustainability. While current evidence supports the mechanistic rationale for combining precision nutrition with GLP-1 receptor agonist therapy, it must be emphasized that direct evidence from prospective clinical trials evaluating such integrated strategies is limited. Most recommendations are based on indirect evidence from general weight-loss or metabolic disease populations, and their efficacy, specifically in GLP-1 RA-treated patients, remains to be demonstrated.
