Dietary fiber and GLP-1 receptor agonists in obesity management: converging mechanisms, interactions, and strategies for durable weight control

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of2obesity by producing substantial and durable weight loss. However, gastrointestinal adverse3effects, including nausea, vomiting, and constipation, are a common, dose-dependent, and4frequent cause of discontinuation. Furthermore, weight regain is typical after drug withdrawal,5reflecting the chronic and relapsing nature of obesity. Long-term adherence is essential but often6constrained by high cost, injection burden, and patient preference. Moreover, the consequences7of chronic GLP-1 receptor activation on gut physiology, microbiota composition, and immune8tolerance remain incompletely defined. In parallel, dietary fibers offer a physiological means9of engaging the same gut–brain axis through microbial fermentation and the stimulation of10endogenous GLP-1. Fibers deliver broad benefits as they strengthen gut barrier function, enrich11short chain fatty acid, and recalibrate immunity toward an anti-inflammatory state. Nevertheless,12weight loss with fiber alone is typically more modest than with GLP-1RAs and depends on the13type, dose, and duration of use. Tolerability can be limited by bloating or gas, particularly if14intake is increased too rapidly. This review critically examines the convergence and divergence15between GLP-1RAs and dietary fibers. We discuss their mechanistic overlaps in appetite control,16metabolism and immune modulation, and highlight potential interactions, such as altered17fermentation dynamics during pharmacological slowing of gastric emptying and the potential18for GLP-1R desensitization. We explore opportunities for fibers to mitigate GLP-1RA-related19adverse effects, support bowel regularity, and stabilize the microbiota during treatment or after20discontinuation. A pragmatic framework is raised to place dietary fiber and lifestyle measures21as the foundation of care, reserves GLP-1RA therapy for highest-risk individuals, and plans for22fiber supplements once pharmacotherapy is reduced. Well-designed trials that combine GLP-231RAs with well-characterized fibers, include microbiome end points, and assess long-term24outcomes are needed to optimize efficacy and reduce dependence on costly pharmacotherapy.