How to recognize gastroparesis in a patient's son who is on Glucagon-like peptide-1 (GLP-1) receptor agonists, such as exenatide (Byetta), liraglutide (Victoza), or dulaglutide (Trulicity)?

Recognizing Gastroparesis in a Patient on GLP-1 Receptor Agonists

If your patient's son is taking a GLP-1 receptor agonist (exenatide, liraglutide, dulaglutide, semaglutide, or tirzepatide), you should suspect drug-induced gastroparesis when he develops nausea, vomiting, early satiety, postprandial fullness, bloating, or upper abdominal pain—these medications directly delay gastric emptying through vagal nerve-mediated pathways. 1, 2

Key Clinical Symptoms to Recognize

The cardinal symptoms of gastroparesis that you must actively screen for include:

• Nausea and vomiting - the most prominent symptoms, occurring in a dose-dependent manner and more frequently with short-acting GLP-1 RAs like exenatide 1, 3
• Early satiety and postprandial fullness - patients report feeling full after eating only small amounts 1, 4
• Bloating and upper abdominal distention - caused by delayed gastric emptying and increased gastric volumes 1
• Upper abdominal pain or discomfort - may be epigastric in location 1
• Weight loss - though this may be confounded by the intended weight loss effect of these medications 1

Critical Physical Examination Findings

When examining the patient, specifically look for:

• Succussion splash - audible splashing sound on auscultation of the abdomen after shaking the patient, highly suggestive of delayed gastric emptying or gastric outlet obstruction 1
• Visible gastric distention in the epigastric region 4
• Signs of dehydration from persistent vomiting 5

Mechanism: Why GLP-1 RAs Cause Gastroparesis

GLP-1 receptor agonists delay gastric emptying through vagal nerve-mediated inhibition of gastric peristalsis while simultaneously increasing pyloric tone. 1 This mechanism leads to:

• Reduced phasic gastric contractions 1
• Increased fasting and postprandial gastric volumes 1
• Reduced gastric acid secretion 1
• Prolonged retention of gastric contents even after extended fasting periods 1, 2

A critical nuance: Short-acting GLP-1 RAs (like exenatide and liraglutide) have more pronounced effects on delaying gastric emptying than long-acting formulations (like semaglutide and dulaglutide), though all formulations can cause this effect. 1, 2

Diagnostic Confirmation

To objectively confirm gastroparesis in this patient:

• Gastric emptying scintigraphy is the gold standard test - it will show delayed gastric emptying if performed while the patient is on the GLP-1 RA 1, 6
• Upper endoscopy should be performed to exclude mechanical gastric outlet obstruction 1, 4
• Gastric ultrasound can assess for retained gastric contents and gastric distension 1, 2

Important caveat: Paracetamol absorption tests are now considered suboptimal for measuring gastric emptying and should not be relied upon. 1

Distinguishing Drug-Induced from Pre-Existing Gastroparesis

The timing of symptom onset is crucial:

• If symptoms began after starting the GLP-1 RA, drug-induced gastroparesis is highly likely 1, 2, 7
• If symptoms were present before initiating the GLP-1 RA, the medication is contraindicated and should be discontinued immediately 1, 8
• GLP-1 RAs are not recommended in patients with severe gastrointestinal disease, including severe gastroparesis 8

Tachyphylaxis Consideration

There is evidence of tachyphylaxis (diminishing effect over time) with continuous GLP-1 RA exposure, suggesting autonomic nervous system adaptation. 1, 2 However:

• Acute and intermittent exposures have more pronounced effects on delaying gastric emptying than continuous infusion 1
• Despite potential tachyphylaxis, patients still experience significantly delayed gastric emptying even after prolonged use 1
• Recent perioperative studies question whether tachyphylaxis is clinically significant, as retained gastric contents are documented even after extended fasting periods 1, 2

Immediate Management Steps

If you suspect drug-induced gastroparesis:

1. Discontinue the GLP-1 RA immediately 1, 7
2. Initiate conservative treatment with gastric decompression (nasogastric suctioning if severe), antiemetics, and prokinetic therapy 7, 5
3. Assess nutritional status and implement dietary modifications (small particle size, reduced fat diet) 1, 5
4. Monitor for resolution - symptoms should improve markedly after discontinuation 7

Common Pitfalls to Avoid

• Do not assume the patient has idiopathic or diabetic gastroparesis without first considering medication-induced causes 1, 9
• Do not continue the GLP-1 RA while investigating gastroparesis symptoms - the medication itself is likely the culprit 1, 2, 7
• Do not rely solely on symptom improvement with antiemetics as evidence against gastroparesis - objective testing with scintigraphy is required 1, 6
• Do not restart GLP-1 RAs in patients who develop gastroparesis, as this is a contraindication to future use 8