Introduction Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now widely used for type 2 diabetes and obesity, two conditions frequently encountered in gastroenterology practice. Their effects extend far beyond glycemic control and weight loss, influencing the gut, pancreas, liver, biliary system, and peri-endoscopic care.
Introduction
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now widely used for type 2 diabetes and obesity, two conditions frequently encountered in gastroenterology practice. Their effects extend far beyond glycemic control and weight loss, influencing the gut, pancreas, liver, biliary system, and peri-endoscopic care. Because these drugs are increasingly prescribed, gastroenterologists need practical, evidence-based guidance on how to use them safely in daily practice.
Why This Position Paper Is Needed
Although GLP-1RAs have shown major cardiometabolic benefits, clinicians continue to face important questions in gastroenterology:
Are they safe in MASLD/MASH and cirrhosis?
Do they increase the risk of GI or pancreatic cancers?
Should they be routinely stopped before upper GI endoscopy?
How should we manage GI side effects, pancreatitis concerns, and gallstone risk?
This position paper from the Italian Society of Gastroenterology (SIGE) addresses these common clinical dilemmas and provides a practical framework for day-to-day management.
Key Takeaways
GLP-1RAs can be safely used in patients with diabetes or obesity and MASLD/MASH.
They appear beneficial, especially in non-cirrhotic MASH, and semaglutide is highlighted as a disease-modifying option in selected patients with F2–F3 fibrosis.
Semaglutide should be considered in adults with non-cirrhotic MASH and moderate-to-advanced fibrosis.
It has shown meaningful benefit in MASH resolution and may improve fibrosis in selected patients.
GLP-1RAs appear safe in cirrhosis.
In patients with cirrhosis plus diabetes or obesity, these agents seem safe and may even reduce hepatic decompensation.
A possible reduction in hepatocellular carcinoma risk is suggested.
This is promising, but the evidence remains weak and largely observational.
GLP-1RAs do not appear to increase the risk of major GI cancers.
Available evidence does not support an increased risk of oesophagal, gastric, or colorectal cancer.
Pancreatic cancer risk does not appear to increase.
In fact, some studies suggest a possible reduction, but this remains uncertain.
Routine discontinuation before upper GI endoscopy is not recommended.
Current evidence does not support stopping GLP-1RAs routinely before gastroscopy.
A liquid diet the day before upper GI endoscopy may be useful in selected cases.
This is particularly relevant for:
patients with nausea, vomiting, or dyspepsia
longer or more complex endoscopic procedures
Suspected retained gastric contents
No extra bowel preparation is required before a colonoscopy.
Standard colonoscopy preparation appears sufficient in most patients receiving GLP-1RAs.
GLP-1RAs do not increase the risk of acute pancreatitis.
This is an important reassurance for clinicians, although caution remains sensible in very high-risk patients.
GLP-1RAs do increase the risk of cholelithiasis.
This is one of the clearest safety signals and should be kept in mind, especially in rapid weight loss or pre-existing biliary risk.
Mild GI adverse events are common, especially early after starting therapy.
Nausea, vomiting, diarrhoea, constipation, and reflux symptoms are the most frequent issues.
GI side effects are usually mild, transient, and dose-dependent.
Most occur early and improve with time and gradual dose escalation.
Severe GI complications are not increased.
Serious events such as major obstruction, perforation, or severe complications are uncommon and not clearly more frequent than with placebo.
GERD symptoms may worsen.
Clinicians should ask about reflux symptoms, particularly in predisposed patients.
Patient education is central to successful use.
Practical advice includes:
smaller meals
avoiding high-fat meals
good hydration
slow dose titration
temporary symptomatic treatment when needed
Dose escalation matters.
Slower titration can improve tolerability and reduce treatment discontinuation.
Evidence quality remains limited for many recommendations.
Much of the guidance is based on low or very low quality evidence, highlighting the need for better prospective studies.
Conclusion
This SIGE position paper supports the growing integration of GLP-1RAs into gastroenterology and hepatology practice. Overall, these drugs appear safe, clinically useful, and increasingly relevant, particularly in patients with obesity, diabetes, and MASLD/MASH. Routine discontinuation before upper endoscopy is generally unnecessary, pancreatitis risk is not increased, and cancer concerns are largely unsupported. The key practical issues are GI tolerability, reflux symptoms, and cholelithiasis, all of which can usually be managed with careful monitoring and thoughtful clinical judgment.
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