Beyond GLP-1 Agonists: Plant-Derived Bioactive Compounds as Adjunctive Strategies for Obesity Management

Background: Obesity has reached epidemic proportions, affecting over one billion adults worldwide. While incretin-based pharmacotherapies-GLP-1 receptor agonists (semaglutide) and dual GIP/GLP-1 agonists (tirzepatide)-have transformed obesity treatment, their use remains limited by high costs, adverse effects, restricted eligibility, and rapid weight regain following discontinuation. Plant-derived bioactive compounds represent a promising complementary approach to address these gaps. Objective: This narrative review synthesizes clinical trial evidence on plant-based interventions for obesity management and examines their potential role as adjunctive strategies before, during, and after incretin-based pharmacotherapy. Methods: A literature search was conducted in PubMed, Scopus, and Web of Science (2012-2026), prioritizing randomized controlled trials in adults with overweight or obesity reporting at least one obesity-related metabolic outcome. Sixty-one studies were selected and classified by efficacy tier based on the magnitude and breadth of observed clinical effects. Results: The strongest evidence supports polyphenol-rich dietary patterns, particularly the green-Mediterranean diet, producing significant reductions in body weight, visceral fat, and cardiometabolic risk markers. Specific extracts-including curcumin, bergamot polyphenols, and Lippia citriodora/Hibiscus sabdariffa combinations-demonstrated clinically meaningful metabolic improvements. Isolated high-dose resveratrol and several single-compound interventions showed limited benefit, largely attributable to poor bioavailability. The most effective compounds acted through multiple pathways, including AMPK activation, gut microbiota modulation, and appetite hormone regulation. Conclusions: Plant-derived bioactive compounds offer a safe, accessible adjunctive strategy for obesity management, particularly relevant for patients ineligible for or discontinuing pharmacotherapy. Future trials should directly evaluate plant-polyphenol combinations alongside GLP-1 receptor agonists.