What laxative is recommended for a patient with type 2 diabetes taking a Glucagon-like peptide-1 (GLP-1) analogue?

Laxative Selection for Patients on GLP-1 Analogues

For patients with type 2 diabetes taking GLP-1 receptor agonists who develop constipation, osmotic laxatives—specifically polyethylene glycol (PEG), lactulose, or lactitol—should be the first-line pharmacological treatment, with bisacodyl or sodium picosulfate reserved for short-term or rescue use. 1, 2

Understanding the Constipation Risk with GLP-1 Analogues

GLP-1 receptor agonists slow gastric emptying and delay gastric transit as part of their mechanism of action, which contributes to their glucose-lowering and weight-reducing effects. 3, 4 This delayed gastric emptying can lead to constipation, particularly with short-acting agents like exenatide and lixisenatide, though the effect on gastric emptying shows tachyphylaxis (reduced effect over time) with long-acting preparations. 3, 4

Stepwise Approach to Managing Constipation

First Step: Lifestyle Modifications

• Begin with dietary fiber supplementation using bulking agents such as psyllium, bran, or methylcellulose before escalating to pharmacological laxatives. 2
• Encourage increased fluid intake and regular physical activity as foundational interventions. 2

Second Step: Osmotic Laxatives (Primary Pharmacological Choice)

Polyethylene glycol (PEG), lactulose, or lactitol should be the first-line laxative agents when lifestyle modifications fail. 1, 2

• Lactulose is dosed at 10-20 g (15-30 mL or 1-2 packets) daily, with potential increase to 40 g (60 mL or 2-4 packets) daily if needed. 1
• Lactulose has a prebiotic effect and demonstrates a "carry-over effect" (continued laxative benefit for 6-7 days after cessation), making it particularly useful for sustained management. 2
• In patients with type 2 diabetes who are not insulin-dependent, lactulose use does not lead to increased blood sugar levels. 1
• The main limitation of lactulose is dose-dependent bloating and flatulence, which may limit tolerability in some patients. 1

Third Step: Stimulant Laxatives (Short-Term or Rescue Therapy)

Bisacodyl or sodium picosulfate should be used for short-term treatment (≤4 weeks of daily use) or as rescue therapy when osmotic laxatives are insufficient. 1, 2

• These agents lead to large increases in complete spontaneous bowel movements (CSBMs) per week (mean difference 2.54,95% CI 1.07-4.01) and spontaneous bowel movements (SBMs) per week (mean difference 4.04,95% CI 2.37-5.71). 1
• Start at a lower dose and titrate upward as tolerated to minimize abdominal cramping and diarrhea. 1
• While long-term use is probably appropriate, current evidence supports primarily short-term or intermittent use. 1

Critical Considerations Specific to Diabetes Management

• The primary aim when managing constipation in diabetic patients on GLP-1 analogues is to optimize both diabetes control and bowel function simultaneously. 2
• Physicians should educate patients about the rationale for laxative use and the potential drawbacks of long-term stimulant laxative use. 2
• Patients should be instructed to contact their physician if short-term use of the prescribed laxative fails to provide relief. 2

When to Consider Advanced Therapies

For severe or treatment-resistant constipation despite the above measures, newer agents such as chloride-channel activators (lubiprostone) or 5-HT4 agonists (prucalopride) can be considered, though these are reserved for refractory cases. 2