What is the recommended constipation protocol for patients on Glucagon-Like Peptide (GLP) medications?

Constipation Management Protocol for Patients on GLP-1 Receptor Agonists

Start with prophylactic stimulant laxatives (senna or bisacodyl 10-15 mg daily) at GLP-1 initiation, as constipation occurs in approximately 50% of patients on these medications due to delayed gastric emptying, and escalate systematically if symptoms develop. 1

Initial Prevention Strategy

• Initiate prophylactic bowel regimen immediately when starting GLP-1 receptor agonists, using a stimulating laxative (senna or bisacodyl) to increase bowel motility, as GLP-1 medications significantly delay gastric emptying and intestinal transit. 1, 2

• Gradually titrate GLP-1 receptor agonists to minimize gastrointestinal side effects when initiating use, and follow up with the healthcare provider if side effects do not resolve over time (a few weeks). 1

• Discontinue any nonessential constipating medications (antacids, anticholinergics, other opioids if applicable). 1

• Encourage increased fluid intake (8-10 ounces with each dose) and physical activity when appropriate. 1, 3

Assessment When Constipation Develops

Before escalating therapy, rule out:

• Fecal impaction (perform digital rectal exam; overflow diarrhea can mimic treatment failure). 1, 4, 3
• Bowel obstruction (assess for abdominal pain, nausea, vomiting; obtain abdominal x-ray if clinically indicated). 4, 3
• Metabolic causes: hypercalcemia, hypokalemia, hypothyroidism. 1
• Gastroparesis (particularly relevant given GLP-1's effect on gastric emptying). 1, 2

Stepwise Treatment Algorithm

Step 1: Stimulant Laxative

• Bisacodyl 10-15 mg daily to three times daily with goal of 1 non-forced bowel movement every 1-2 days. 1, 4, 3
• Alternative: Senna (docusate addition not necessary based on evidence). 1

Step 2: Add Osmotic Laxative if Constipation Persists

• Polyethylene glycol (PEG) 17 g daily is the preferred osmotic agent with durable 6-month response. 4
• Magnesium citrate 240 mL (8 oz) daily as alternative for patients who cannot tolerate PEG. 4
  • Critical contraindication: Avoid in renal impairment due to fatal hypermagnesemia risk. 4, 3
  • Also contraindicated in gastrointestinal diseases (ileus, ischemic colitis) even with normal renal function. 4
• Alternative osmotic agents: Lactulose 30-60 mL twice to four times daily, or magnesium hydroxide 30-60 mL daily to twice daily (avoid in renal insufficiency). 4, 3

Step 3: Consider Prokinetic Agent

• Metoclopramide if gastroparesis is suspected, given GLP-1's known effect of slowing gastric emptying. 1, 2
• Alternative: Erythromycin for refractory cases. 1

Step 4: For Impaction

• Glycerine suppository or bisacodyl suppository (one rectally daily to twice daily). 1, 3
• Manual disimpaction with pre-medication (analgesic ± anxiolytic) if needed. 3
• Avoid rectal interventions in neutropenic or thrombocytopenic patients. 4

GLP-1-Specific Considerations

The delayed gastric emptying caused by GLP-1 receptor agonists is dose-dependent and shows tachyphylaxis with long-term use of short-acting preparations or with long-acting formulations. 2

• Patients on higher doses for weight loss (vs. diabetes management) may experience more pronounced gastric stasis. 1
• GLP-1 receptor agonists retard gastric emptying of both solids and liquids, with effects most pronounced in the first 30-60 minutes post-dose. 2
• Weekly GLP-1 formulations can be taken at any time regardless of meals, while daily/twice-daily formulations should be taken premeal. 1

Common Pitfalls to Avoid

• Do not add stool softeners alone (docusate) without stimulant laxatives, as evidence shows no additional benefit. 1
• Do not use osmotic laxatives in suspected bowel obstruction—this is an absolute contraindication. 4
• Do not assume fiber supplementation alone will suffice—GLP-1-induced constipation requires active motility stimulation. 1
• Do not overlook renal function before prescribing magnesium-based laxatives, as hypermagnesemia can be fatal. 4, 3
• Reassess after 4 weeks if constipation persists despite initial interventions, as this may indicate need for alternative diagnosis or advanced therapies. 4

Monitoring and Follow-Up

• Goal: 1 non-forced bowel movement every 1-2 days. 1, 4
• If gastrointestinal side effects from GLP-1 do not resolve within a few weeks, follow up with prescribing provider to consider dose adjustment or medication change. 1
• Document symptoms of nausea, vomiting, or abdominal distention, as these may indicate more severe gastric retention requiring intervention. 1