What is the recommended management for constipation caused by Zepbound (tirzepatide)?

Management of Zepbound (Tirzepatide)-Induced Constipation

Polyethylene glycol (PEG) is the recommended first-line treatment for constipation caused by Zepbound (tirzepatide), with a goal of achieving one non-forced bowel movement every 1-2 days. 1, 2

Understanding Tirzepatide-Related Constipation

Tirzepatide (Zepbound) is a dual GIP/GLP-1 receptor co-agonist that commonly causes gastrointestinal adverse effects, including constipation. Recent meta-analyses have confirmed that constipation is significantly more common with tirzepatide compared to placebo and insulin 3. Understanding this mechanism helps guide appropriate management strategies.

Treatment Algorithm

First-Line Approaches:

1. Polyethylene glycol (PEG): 17g daily mixed in 8 ounces of water 1, 2

   • Can be titrated as needed
   • Has demonstrated safety and efficacy for up to 12 months
   • Provides moderate certainty of evidence for effectiveness

2. Lifestyle modifications (to be implemented alongside medication):

   • Increase fluid intake, particularly in patients with low baseline fluid consumption
   • Increase physical activity if appropriate 1
   • Ensure adequate dietary fiber intake, though supplemental fiber alone is unlikely to resolve opioid-induced constipation 1

Second-Line Approaches (if inadequate response to PEG):

1. Add stimulant laxative: Bisacodyl 10-15 mg daily to three times daily 1, 2

   • Goal: One non-forced bowel movement every 1-2 days
   • Available as oral tablets (onset 6-12 hours) or suppositories (onset 30-60 minutes)

2. Rule out complications:

   • Check for impaction, especially if diarrhea accompanies constipation (overflow around impaction)
   • Consider abdominal X-ray to rule out obstruction 1

Third-Line Approaches (for persistent constipation):

1. Add or switch to other laxatives:

   • Lactulose: 30-60 mL twice to four times daily 1
   • Magnesium citrate: 8 oz daily (use with caution in renal insufficiency) 1, 2
   • Sorbitol: 30 mL every 2 hours × 3, then as needed 1

2. Consider prescription medications for refractory cases:

   • Linaclotide: 72-145 μg daily (can be titrated up to 290 μg) 1, 2
   • Lubiprostone: A chloride channel activator with strong evidence for efficacy 1

Monitoring and Assessment

• Assess response to treatment after 1-2 days 2
• Monitor for adverse effects such as abdominal cramping or diarrhea
• Ensure adequate fluid intake to prevent electrolyte imbalances
• Consider discontinuing any non-essential constipating medications 1

Special Considerations

• Risk of complications: Recent evidence suggests tirzepatide may be associated with colonic ischemia in rare cases 4. Monitor for severe abdominal pain, bloody stools, or other concerning symptoms.
• Contraindications: Avoid Fleet enemas in patients with neutropenia, thrombocytopenia, intestinal obstruction, recent colorectal surgery, or severe colitis 2.
• Avoid ineffective approaches: Supplemental medicinal fiber (psyllium) alone is unlikely to be effective for medication-induced constipation 1.

By following this structured approach to managing tirzepatide-induced constipation, patients can achieve relief while minimizing complications and maintaining the benefits of their Zepbound therapy.