Gastrointestinal Adverse Effects of GLP-1 and Dual GLP-1/GIP Receptor Agonists: A Comprehensive Update in Diabetic and Obese Populations

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/GIP receptor agonists are highly effective agents for the treatment of type 2 diabetes and obesity. However, gastrointestinal (GI) adverse events remain the most common limitations to long-term therapy. Methods: A narrative review with a structured literature search was conducted using PubMed, Embase, and Cochrane Library databases from inception to March 2025. Randomized controlled trials, observational studies, meta-analyses, and pharmacovigilance reports evaluating GI adverse effects of GLP-1-based therapies were included. Results: Nausea, vomiting, diarrhea, and constipation were the most frequently reported GI adverse events, generally dose-dependent and transient. Delayed gastric emptying, gastroparesis-like symptoms, intestinal obstruction, biliary disease, and pancreatic safety concerns were variably reported, with heterogeneous and sometimes conflicting evidence across studies. Conclusion: GLP-1-based therapies are associated with predictable GI adverse effects, most of which are mild to moderate and manageable. Serious complications appear rare, but evidence remains inconsistent. Individualized risk assessment, patient education, and careful dose titration are essential for optimizing long-term tolerability.