How to manage constipation induced by Mounjaro (tirzepatide)?

Management of Mounjaro (Tirzepatide)-Induced Constipation

Start with polyethylene glycol (PEG) 17 g once daily as first-line therapy, as it has the strongest evidence for efficacy in chronic constipation with moderate certainty of evidence. 1

Initial Assessment and Non-Pharmacologic Measures

Before initiating laxative therapy, assess for:

• Bowel obstruction or fecal impaction (perform physical exam; consider abdominal x-ray if diarrhea accompanies constipation, suggesting overflow) 1
• Other contributing causes: hypercalcemia, hypokalemia, hypothyroidism, diabetes mellitus, or other constipating medications 1

Implement lifestyle modifications concurrently:

• Increase fluid intake to at least 8-10 ounces with each dose of fiber or laxative, particularly if baseline fluid intake is low 1
• Increase physical activity if feasible 1
• Consider fiber supplementation (psyllium) only for mild constipation in patients with adequate fluid intake, though evidence is limited and fiber alone is unlikely to control medication-induced constipation 1

Pharmacologic Treatment Algorithm

First-Line: Osmotic Laxative

• Polyethylene glycol (PEG) 17 g mixed in 8 ounces of liquid once daily 1
• PEG increases complete spontaneous bowel movements by 2.90 per week and has durable response over 6 months 1
• Side effects include abdominal distension, loose stools, flatulence, and nausea 1
• Goal: 1 non-forced bowel movement every 1-2 days 1

Second-Line: Add Stimulant Laxative

If constipation persists after 1-2 weeks of PEG:

• Add bisacodyl 10-15 mg orally daily to three times daily 1
• Alternative: Senna 2 tablets twice daily (maximum 8-12 tablets per day) 1
• Note: Stool softeners (docusate) alone are not necessary and lack evidence of benefit 1

Third-Line: Additional Osmotic or Stimulant Agents

If constipation remains refractory:

• Lactulose 30-60 mL twice to four times daily 1
• Magnesium hydroxide 30-60 mL once to twice daily 1
• Magnesium citrate 8 oz daily 1
• Sorbitol 30 mL every 2 hours × 3, then as needed 1

Fourth-Line: Rectal Interventions

For severe or refractory constipation:

• Bisacodyl suppository 10 mg rectally once to twice daily 1
• Glycerin suppository 1
• Fleet, saline, or tap water enema 1

Fifth-Line: Prokinetic Agent

If gastroparesis is suspected (early satiety, bloating, nausea):

• Metoclopramide 10-20 mg orally four times daily 1

Important Caveats

Tirzepatide commonly causes gastrointestinal side effects including constipation as part of its mechanism of action (delayed gastric emptying), similar to other GLP-1 receptor agonists 2, 3. These effects are dose-dependent and more common at higher doses 3.

Do not discontinue tirzepatide solely for constipation unless it becomes severe or refractory to aggressive laxative therapy, as the metabolic benefits (glycemic control and weight loss) are substantial 3.

Rule out serious complications: While rare, tirzepatide has been associated with acute pancreatitis 4, 5 and colonic ischemia 6. If severe abdominal pain, nausea, vomiting, or bloody stools develop, immediately evaluate for these conditions rather than attributing symptoms solely to constipation.

Avoid bulk-forming agents (Metamucil) as monotherapy for medication-induced constipation, as they are ineffective without adequate fluid intake and physical activity 1.