What are the potential complications in the epigastric region when using Glucagon-like peptide-1 (GLP-1) receptor agonists?

Complications in the Epigastric Region When Using GLP-1 Receptor Agonists

GLP-1 receptor agonists commonly cause gastrointestinal adverse effects in the epigastric region, with nausea, vomiting, and dyspepsia being the most frequently reported complications that can significantly impact patient quality of life. 1

Common Epigastric Complications

• Nausea and vomiting: These are dose-dependent and occur more frequently with short-acting than long-acting GLP-1 receptor agonists 1
• Dyspepsia: Common epigastric discomfort that can persist during treatment 1
• Gastroesophageal reflux: Can develop as GLP-1 receptor agonists delay gastric emptying 1, 2
• Abdominal pain: Reported in up to 57.6% of patients using GLP-1 receptor agonists in real-world data 3
• Acute pancreatitis: A rare but serious complication linked particularly to exenatide use 1, 4

Mechanism of Epigastric Complications

GLP-1 receptor agonists cause epigastric symptoms primarily through:

• Delayed gastric emptying: These medications slow the movement of food through the stomach, leading to prolonged gastric retention 1
• Central effects on appetite regulation: They act on the arcuate nucleus in the hypothalamus and the area postrema and nucleus tractus solitarius in the medulla, affecting satiety signals 1
• Effects on vagal nerve endings: Receptors on the afferent vagal nerve endings in the intestinal mucosa generate signals that can contribute to gastrointestinal symptoms 1

Risk Factors and Severity

• Dose-related: Higher doses are associated with increased risk of gastrointestinal adverse events 5, 6
• Background medication: Concomitant metformin use significantly increases the risk of nausea (p=.04) and vomiting (p=.0009) 5
• Medication type: Semaglutide has shown the greatest risk of nausea (ROR 7.41), diarrhea (ROR 3.55), vomiting (ROR 6.67), and constipation (ROR 6.17) compared to other GLP-1 receptor agonists 2
• Timing: Most gastrointestinal adverse events tend to occur within the first month of treatment 2

Serious Epigastric Complications

Acute Pancreatitis

• Linked to GLP-1 receptor agonist use, particularly exenatide, in FDA Adverse Event reporting system 1
• Risk appears to be dose-dependent with higher cumulative doses associated with increased pancreatitis risk 6
• Liraglutide has shown the highest risk of pancreatitis in some analyses (ROR 32.67) 2
• Current guidelines from the American Association of Clinical Endocrinologists recommend using GLP-1 receptor agonists with caution in patients with a history of pancreatitis 1

Gallbladder Disorders

• GLP-1 receptor agonists may increase the risk of gallbladder disease, including acute cholecystitis 1, 4
• FDA drug labeling for liraglutide reports cholelithiasis in 0.3% of patients and cholecystitis in 0.2% of patients 4
• Post-marketing reports include cases requiring cholecystectomy 4, 7

Pulmonary Aspiration Risk

• Emerging evidence suggests increased risk of pulmonary aspiration under anesthesia in patients using GLP-1 receptor agonists 1, 4
• This risk is attributed to delayed gastric emptying, even with appropriate pre-operative fasting 1
• Multiple case reports document regurgitation and pulmonary aspiration in patients on GLP-1 receptor agonists despite extended fasting periods (up to 18-20 hours) 1

Management of Epigastric Complications

• Start at low dose and titrate slowly: This approach helps improve gastrointestinal tolerability 1
• Reduce meal size: Smaller meals may help minimize symptoms 1
• Limit alcohol and carbonated drinks: These can exacerbate gastrointestinal reflux 1
• Avoid high-fat diet: High-fat foods can worsen symptoms 1
• Avoid in gastroparesis: GLP-1 receptor agonists should be avoided in patients with pre-existing gastroparesis 1
• Monitor for pancreatitis: Be vigilant for signs of pancreatitis, especially in patients with risk factors 1, 6

Special Considerations

• Perioperative period: Consider temporary discontinuation before elective surgery requiring general anesthesia due to aspiration risk 1, 4
• Concomitant medications: Absorption of other oral medications may be affected due to delayed gastric emptying 1
• Renal function: Use with caution in patients with severe renal impairment as GI losses can worsen renal function 8

By understanding these potential epigastric complications and implementing appropriate management strategies, clinicians can optimize the use of GLP-1 receptor agonists while minimizing adverse effects on patient quality of life.