Nutritional Approaches to Enhance GLP-1 Analogue Therapy in Obesity: A Narrative Review

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are highly effective in the management of obesity; however, their efficacy and tolerability may be further optimized through complementary nutritional strategies. Such interventions may address key challenges associated with GLP-1RA therapy, including gastrointestinal adverse effects, lean mass loss, and reduced long-term adherence leading to weight regain. Evidence from preclinical and clinical studies indicates that omega-3 polyunsaturated fatty acids may enhance the metabolic benefits of GLP-1RAs and attenuate lean mass loss, primarily via anti-inflammatory pathways and modulation of protein synthesis. Synergistic effects have also been reported with other bioactive compounds—such as flavonoids and anthocyanins, which improve metabolic outcomes; probiotics and prebiotics, which may alleviate gastrointestinal intolerance; and high-quality protein sources, which support body composition preservation. Collectively, these findings suggest that nutritional adjuncts may complement GLP-1RA therapies through convergent physiological mechanisms, including the regulation of inflammation, gut microbiome composition, and cellular metabolism. While current data highlight the promise of integrated pharmaco-nutritional strategies as adjuncts to GLP-1-based obesity therapy, further randomized controlled trials are needed to establish the most effective interventions and protocols.