Nutrition Strategies for Next-Generation Incretin Therapies: A Systematic Scoping Review of the Current Evidence

Abstract

Next-generation incretin therapies, including semaglutide and tirzepatide, have transformed obesity and Type 2 diabetes management. However, evidence-based nutritional strategies to support safe and effective use of these agents remain limited. To address this gap, we conducted a systematic scoping review across five databases of studies published between January 2015 and April 2025 to map and appraise clinical trials incorporating nutritional interventions or dietary assessments during semaglutide or tirzepatide therapy in adults with obesity or Type 2 diabetes. Eligible studies included adults receiving semaglutide or tirzepatide with either an active dietary intervention or measured nutrition-related outcomes. Study quality was assessed using established tools. Twelve studies were included: 10 randomized controlled trials, one non-randomized comparative study, and one cross-sectional observational study. Interventions ranged from structured very-low-energy or ketogenic diets to general lifestyle counseling and observational dietary assessments. Across studies, energy intake decreased by 24% to 39%, but lean tissue loss accounted for up to 40% of total weight reduction. Only three studies involved nutrition professionals, and systematic assessment of protein or micronutrient intake was rare. One observational study found widespread nutrient inadequacies and limited access to dietetic support. Despite the effectiveness of semaglutide and tirzepatide for weight loss, evidence on optimal dietary strategies is sparse. Early dietitian involvement, high-protein, nutrient-dense diets, and routine nutritional monitoring should be prioritized. Robust trials are needed to define best practice for integrating dietary care alongside pharmacotherapy.