Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists, such as tirzepatide, have transformed the management of type 2 diabetes and obesity through durable glycemic control, weight reduction, and cardiovascular protection. However, their widespread use has revealed a high incidence of gastrointestinal adverse events, particularly dyspepsia and gastroparesis-like symptoms. While most effects are transient, a significant subset of patients develop persistent intolerance, often leading to misdiagnosis, unnecessary investigations, or premature treatment discontinuation. Current therapeutic options remain limited, with guidelines offering little direction for managing symptoms, in this subset of dyspeptic patients. This growing clinical challenge highlights the urgent need for structured strategies, including risk stratification, tailored dose titration, and multidisciplinary care, to balance metabolic efficacy with gastrointestinal tolerability.
Authors
Masulli, Maria; Tack, Jan; Esposito, Giuseppe; Sarnelli, Giovanni