Systematic review of gastrointestinal adverse effects associated with obesity therapies including incretin-based pharmacotherapy (tirzepatide, semaglutide, liraglutide), covering prevalence, mechanisms, and management strategies for nausea, diarrhea, constipation, GERD, and cholelithiasis. Provides evidence-based management guidance for the most common adherence-limiting adverse effects. Delivers a clinically actionable synthesis of GI adverse event management for tirzepatide—providing prescribers with evidence-based strategies for the GI complications that account for most dose reductions and treatment discontinuations in clinical practice.
Abstract
Obesity management, whether lifestyle-based, pharmacological, or surgical, is frequently associated with gastrointestinal adverse effects (GI AEs) that may impact treatment adherence and patient quality of life. With the increasing use of incretin-based anti-obesity medications (AOMs), they have gained particular clinical relevance. This review aims to explore current evidence on the prevalence, underlying mechanisms, and management strategies for GI AEs associated with obesity therapies, with a particular focus on nausea, diarrhea, constipation, gastroesophageal reflux and cholelithiasis. A search of PubMed and Scopus was conducted for articles published between 2006 and 2025. Eligible studies included randomized controlled trials, observational studies, and narrative or systematic reviews reporting on GI AEs in the context of obesity treatments, especially those involving incretin-based AOMs. Clinical trial data on AOMs indicate that GI AEs are reported in 65-84% of patients treated with liraglutide, semaglutide or tirzepatide, with the most common being nausea and diarrhea. These symptoms are primarily attributed to altered gastric motility and hormone-mediated changes in appetite signaling. Preventive strategies such as slow dose titration, dietary counseling, and supportive medications are commonly recommended to support tolerability and treatment continuation. GI AEs remain a common and often underestimated barrier to effective obesity management. Early recognition and structured management are essential to long-term success. Clinicians should incorporate anticipatory counseling and shared decision-making at treatment initiation to set realistic expectations, optimize tolerability, and support adherence.