Can semaglutide (GLP‑1 receptor agonist) cause melena or black tarry stools?

Can Semaglutide Cause Dark Stools?

Semaglutide does not directly cause melena (black, tarry stools from upper gastrointestinal bleeding), but it significantly increases the risk of conditions that can lead to dark stools, particularly through its effects on the gastrointestinal tract and gallbladder. 1

Understanding the Mechanism

Semaglutide affects gastrointestinal function through several pathways that could indirectly lead to dark stools:

• Delayed gastric emptying is a primary mechanism of action, reducing gastric peristalsis and increasing pyloric tone through vagal pathways, which can lead to gastric distension and increased gastric volumes 2, 3
• Reduced gastric acid secretion occurs as part of the drug's effect on the upper GI tract 2
• Increased risk of gastrointestinal ulceration has been documented, with case reports showing duodenal ulcers developing in patients on semaglutide therapy 4

Serious Conditions That Can Cause Dark Stools

Gastrointestinal Bleeding

• A documented case report describes a patient on semaglutide who developed melena (true dark, tarry stools indicating upper GI bleeding) along with two duodenal ulcers, presenting with epigastric pain, severe diarrhea, and syncope 4
• This represents actual upper gastrointestinal bleeding that would produce black, tarry stools characteristic of melena 4

Gallbladder Disease

• Semaglutide increases the risk of cholelithiasis (gallstones) and cholecystitis by approximately 38% compared to placebo, which can occasionally lead to bleeding into the biliary tract 1
• Biliary disease is an established risk with semaglutide and should be monitored 1

Pancreatitis

• While causality has not been definitively established, pancreatitis has been reported with semaglutide and can occasionally cause gastrointestinal bleeding 1

Other Gastrointestinal Effects That May Confuse the Picture

• Constipation is a significant adverse effect of semaglutide, with a risk ratio of 6.17, which can lead to hard, dark stools that are NOT melena but may appear darker than normal 2
• Diarrhea is a recognized side effect occurring in 12-32% of patients, which is typically not associated with dark stools unless bleeding is present 1
• Most gastrointestinal adverse events are mild-to-moderate and transient, occurring primarily during dose escalation 1

Critical Clinical Approach

If you observe dark stools while on semaglutide, you must immediately distinguish between:

1. True melena (black, tarry, sticky stools with a characteristic foul odor indicating upper GI bleeding) – requires immediate medical evaluation 4
2. Dark but formed stools from constipation or dietary factors (iron supplements, bismuth, certain foods) – less urgent but should still be evaluated 2

Red Flag Symptoms Requiring Immediate Evaluation

• Persistent severe abdominal pain (may indicate pancreatitis or peptic ulcer) 2, 1
• Right upper quadrant pain with fever (suggests cholecystitis) 1
• Weakness, syncope, or signs of anemia (indicates significant blood loss) 4
• Epigastric pain with melena (suggests peptic ulcer disease) 4

Monitoring Recommendations

• Assess bowel movement frequency and consistency at each follow-up visit while on semaglutide 3
• Monitor for signs of gallbladder disease given the 38% increased risk 1
• Evaluate for gastrointestinal bleeding if dark stools develop, particularly if accompanied by abdominal pain, weakness, or other concerning symptoms 4
• Consider gastric ultrasound if severe symptoms develop, particularly before any procedural sedation 3

Common Pitfall to Avoid

Do not assume dark stools are simply a benign side effect of constipation from semaglutide – while constipation is common, true melena represents a serious complication requiring immediate discontinuation of the medication and urgent gastroenterological evaluation 2, 4