How to manage constipation in patients taking GLP-1 (Glucagon-like peptide-1) receptor agonists, such as liraglutide (Victoza) or semaglutide (Ozempic)?

Managing Constipation in Patients Taking GLP-1 Receptor Agonists

Constipation is a recognized dose-dependent adverse effect of GLP-1 receptor agonists that should be managed through slow dose titration, dietary modifications, and standard constipation therapies while continuing the medication. 1

Understanding the Mechanism

GLP-1 receptor agonists cause constipation through their effects on gastrointestinal motility:

• GLP-1 receptors on the myenteric plexus activate nitrergic pathways that inhibit vagal activity on the gut, leading to reduced phasic gastric contractions and delayed gastric emptying. 1
• This mechanism affects the entire gastrointestinal tract, not just the stomach, contributing to constipation as a common adverse effect. 1
• The effect is dose-dependent and occurs more frequently with short-acting formulations than long-acting preparations. 1

Comparative Risk Among Different GLP-1 Agonists

Real-world data shows significant differences in constipation risk:

• Semaglutide carries the highest risk of constipation (ROR 6.17; 95% CI 5.72-6.66) compared to other GLP-1 receptor agonists. 2
• Liraglutide, dulaglutide, and semaglutide are all significantly associated with gastrointestinal adverse events including constipation. 2
• Most gastrointestinal adverse events, including constipation, tend to occur within the first month of treatment. 2

Management Strategy

Initial Prevention Approach

Start with slow dose titration to minimize gastrointestinal side effects: 1

• Begin at the lowest available dose and increase gradually over weeks to months
• This approach is specifically recommended to increase gastrointestinal tolerability 1

Dietary Modifications

Implement specific dietary changes to reduce constipation risk: 1

• Reduce meal size 1
• Avoid high-fat diet 1
• Limit alcohol and carbonated drinks 1
• Increase fiber intake through diet or supplementation (general medical knowledge)

Standard Constipation Management

Use conventional constipation therapies while continuing GLP-1 therapy:

• Osmotic laxatives (polyethylene glycol, lactulose) as first-line agents
• Stimulant laxatives (senna, bisacodyl) for refractory cases
• Stool softeners (docusate) for symptomatic relief
• Adequate hydration (at least 8 glasses of water daily)

When to Consider Medication Adjustment

Avoid GLP-1 receptor agonists entirely in patients with pre-existing gastroparesis. 1

If constipation becomes severe or refractory despite conservative measures:

• Consider switching from semaglutide to a GLP-1 agonist with lower constipation risk 2
• Evaluate for dose reduction if glycemic control and weight loss goals permit
• Assess for other contributing medications or conditions

Common Pitfalls to Avoid

• Do not discontinue GLP-1 therapy prematurely for mild constipation - most gastrointestinal adverse events are manageable with supportive care and often improve with continued use due to tachyphylaxis. 1
• Do not ignore severe or persistent constipation - while rare, serious complications like ileus can occur. 3
• Do not assume all GLP-1 agonists have equal constipation risk - semaglutide has significantly higher rates than other agents. 2

Monitoring Considerations

• Assess bowel movement frequency and consistency at each follow-up visit
• Monitor for signs of bowel obstruction (severe abdominal pain, distension, inability to pass gas)
• Consider gastric ultrasound if severe symptoms develop, particularly before any procedural sedation 4