What could be causing floating stools in a patient with normal liver enzymes and lipase levels, and a history of GLP-1 (Glucagon-like peptide-1) receptor agonist use?

Floating Stools in Context of Recent GLP-1 Use

The floating stools are most likely related to delayed gastric emptying and altered gastrointestinal motility from your recent GLP-1 receptor agonist use, which can persist for weeks after discontinuation, particularly with long-acting formulations. Normal lipase and liver enzymes effectively rule out acute pancreatic insufficiency and hepatobiliary disease as causes.

Primary Mechanism: GLP-1-Induced Gastrointestinal Dysmotility

GLP-1 receptor agonists fundamentally alter gastrointestinal function through multiple mechanisms that can explain your symptoms:

• GLP-1 receptor activation delays gastric emptying through vagal nerve-mediated pathways, reduces phasic gastric contractions, increases both fasting and postprandial gastric volumes, and reduces gastric acid secretion 1
• These effects lead to retained gastric contents and undigested food, which has been documented even 10-14 days after discontinuation in endoscopy studies 2
• The motility changes affect the entire gastrointestinal tract, not just the stomach, contributing to altered transit times and stool characteristics 1

The persistence of symptoms two weeks after discontinuation is consistent with the pharmacology of long-acting GLP-1 receptor agonists:

• Long-acting formulations (semaglutide, dulaglutide) have more prolonged effects on gastrointestinal motility compared to short-acting agents 1
• Studies show gastric residue in patients with median treatment duration of 57 months, even after appropriate fasting periods 2
• The delayed gastric emptying effect can persist because these medications have extended half-lives and tissue distribution 2

Why Normal Lipase Rules Out Pancreatic Insufficiency

Your normal lipase effectively excludes exocrine pancreatic insufficiency as the cause of floating stools:

• While GLP-1 receptor agonists can elevate lipase levels (more commonly than amylase), your normal values indicate no pancreatic inflammation or dysfunction 3
• True pancreatic insufficiency causing steatorrhea (fat malabsorption leading to floating stools) would require loss of >90% of pancreatic function and would show elevated lipase if acute or other clinical signs if chronic
• The concern about early pancreatic cancer is not supported by normal lipase and the temporal relationship to GLP-1 use

Differential Considerations Beyond GLP-1 Effects

While GLP-1 effects are the primary explanation, consider these additional factors:

• Gallbladder dysfunction: GLP-1 receptor agonists are associated with cholelithiasis and cholecystitis, which could impair bile flow and fat digestion 4
• Dietary changes: Rapid gastric emptying delay can alter fat absorption patterns, and patients often modify their diet while on GLP-1 therapy 1
• Increased gas content: Delayed gastric emptying and altered motility can increase intestinal gas production, contributing to stool buoyancy independent of fat malabsorption 1

Clinical Management Approach

Immediate reassurance is warranted given normal laboratory values and clear temporal relationship to medication:

• The floating stools represent altered gastrointestinal transit and possibly incomplete digestion from delayed gastric emptying, not pancreatic cancer 2, 1
• Symptoms should gradually improve over the next 2-4 weeks as the medication fully clears from your system
• Monitor for resolution; if symptoms persist beyond 4-6 weeks post-discontinuation, further evaluation would be indicated

If symptoms are distressing or persist, consider:

• Reducing meal size and avoiding high-fat diets to minimize the burden on delayed gastric emptying 1, 5
• Right upper quadrant ultrasound to evaluate for gallbladder disease if any associated right upper quadrant pain, given the association between GLP-1 use and cholelithiasis 4
• Gastric emptying scintigraphy (gold standard) only if symptoms persist beyond expected clearance time to document delayed gastric emptying 1

Key Pitfall to Avoid

Do not pursue extensive pancreatic imaging or tumor markers based solely on floating stools with normal lipase in the context of recent GLP-1 use. The evidence clearly shows that GLP-1 receptor agonists cause retained gastric contents and gastrointestinal dysmotility that can persist after discontinuation 2, 1. This is the most parsimonious explanation for your symptoms and does not warrant invasive investigation at this time.