Primary care-focused review of GI adverse effects from GLP-1 and GIP receptor agonists (including tirzepatide), covering nausea, vomiting, diarrhea, constipation, gastroparesis, biliary disease, and the pancreatitis evidence, with practical management strategies for the 40–70% of patients experiencing GI side effects. Bridges the gap between specialist prescribing and primary care management. Provides primary care physicians with evidence-based strategies for managing GI adverse events from tirzepatide and GLP-1 RAs—the most common reason for dose reduction, discontinuation, and patient dissatisfaction in an era when primary care is the dominant setting for incretin therapy prescribing.
Abstract
Type 2 diabetes and obesity drive significant morbidity, mortality, and health care costs in the United States. Clinicians increasingly prescribe glucagon-like peptide 1 (GLP1) receptor agonists (GLP1-RAs) and dual GLP1 and glucose-dependent insulinotropic polypeptide receptor agonists to treat these and other conditions. However, 40% to 70% of patients experience gastrointestinal adverse effects, such as nausea, vomiting, diarrhea, constipation, delayed gastric emptying, and biliary disease. High-quality studies have not yet confirmed an increased risk of pancreatitis. Management of gastrointestinal symptoms should start with dietary modifications-smaller, more frequent meals; adequate hydration; and avoidance of high-fat or high-sugar foods. If symptoms persist, patients can trial several medications for symptom relief. For patients undergoing elective endoscopy, clinicians should engage in shared decision-making to weigh the risks of continuing vs temporarily discontinuing incretin-based therapies. For endoscopy, GLP1-RA use is associated with a higher incidence of retained gastric contents but not with increased aspiration risk. Long-acting formulations (eg, semaglutide, dulaglutide, and tirzepatide, among others), high doses, procedures during dose escalation, and gastrointestinal comorbidities that delay gastric emptying raise risk of retained gastric contents. In most cases, clinicians can continue GLP1-RAs periprocedurally, although a 24-hour liquid diet may benefit high-risk patients. For colonoscopy, withholding GLP1-RAs may reduce the risk of inadequate bowel preparation, but further research should clarify the magnitude of this risk.
Authors
Saha, Bibek; Kamalumpundi, Vijayvardhan; Codipilly, Don C