Preprints.org · Nov 13, 2026

Nutritional Strategies for Managing Gastrointestinal Adverse Effects Associated with GLP-1 Receptor Agonist and Dual GIP/GLP-1 Receptor Agonist Therapy: A Narrative Review with Practical Recommendations

By Baldassari G, Siragusa N, Ferrario L et al.

Incretin-based therapies have marked a turning point in the treatment of obesity, because of their demonstrated effects on body weight and beyond, including numerous cardi-ometabolic outcomes. Within obesity management, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists (GIP/GLP-1 RAs) are, to date, the most effective pharma-cological strategies. A growing body of evidence, however, points to limited tolerability caused by gastrointestinal adverse effects, which may impair treatment adherence and reduce both quality of life and the nutritional adequacy of patients’ diets. These effects, which include nausea, vomiting, dyspepsia, constipation, diarrhea, and abdominal bloating, are often observed in the early phases of treatment and during dose escalation. Yet the dietary recommendations available for their management remain fragmentary and inaccurate. This narrative review sets out to analyze the main pathophysiological mechanisms un-derlying the gastrointestinal manifestations of incretin-based therapies and to gather the available evidence on nutritional strategies for their prevention and management. We address the contribution of the GLP-1 and GIP systems to the modulation of gastroin-testinal motility, appetite, and clinical tolerability, with attention to the differences cur-rently recognized between selective GLP-1 RAs and dual GIP/GLP-1 RAs. We then present practical, symptom-specific recommendations covering meal distribution, mod-ulation of fat and fiber intake, hydration, food choices, and the overall quality of diet and lifestyle. Finally, we discuss the key role of nutrition in preservation adequate energy and protein intake, preventing micronutrient deficiencies, and conserving muscle mass throughout treatment with incretin-based therapies. A structured, personalized, symptom-oriented nutritional approach could improve the tolerability of these therapies, optimize clinical outcomes, and support their efficacy over the long term.

doi.org/10.20944/preprints202611.1418.v1Open accessInterventions