Does Glucagon-like peptide-1 (GLP-1) cause constipation?

From the Guidelines

Yes, GLP-1 receptor agonists can cause constipation in some patients, affecting approximately 5-20% of people taking these medications, as reported in a recent study 1. This occurs because GLP-1 medications slow down gastric emptying and intestinal transit time, which helps create feelings of fullness but can also lead to slower movement of stool through the digestive tract.

Key Points to Consider

• The mechanism of action of GLP-1 receptor agonists, such as slowing down gastric emptying, can contribute to constipation 1.
• Constipation is listed as a common adverse effect of GLP-1 receptor agonists in Table 2 of a recent study 1, with management suggestions including avoiding high-fat diets.
• If you experience constipation while taking a GLP-1 medication, increasing your water intake, consuming more dietary fiber, engaging in regular physical activity, and maintaining a consistent bathroom routine can help manage this side effect.
• In more persistent cases, your healthcare provider might recommend a gentle stool softener or laxative, as constipation can be a dose-dependent side effect that is more frequent with short-acting than long-acting drugs 1.
• Most constipation issues tend to improve as your body adjusts to the medication over the first few weeks of treatment, but you should inform your healthcare provider if constipation becomes severe or is accompanied by significant abdominal pain.

Management and Prevention

• Increasing water intake and consuming more dietary fiber can help manage constipation caused by GLP-1 receptor agonists.
• Engaging in regular physical activity and maintaining a consistent bathroom routine can also help alleviate constipation symptoms.
• Avoiding high-fat diets, as suggested in a recent study 1, may also help prevent or manage constipation.

From the FDA Drug Label

Constipation 2 10 Gastrointestinal: ... constipation, ...

GLP-1 and Constipation: Exenatide, a GLP-1 receptor agonist, may cause constipation. According to the drug label, constipation was reported in 10% of exenatide-treated patients compared to 2% of placebo-treated patients in a 30-week placebo-controlled study 2. Additionally, constipation is listed as a gastrointestinal adverse reaction in the post-marketing experience section of the label.

• Key points:
  • Constipation reported in 10% of exenatide-treated patients
  • Constipation listed as a gastrointestinal adverse reaction in post-marketing experience
  • Exenatide slows gastric emptying, which may contribute to constipation 2

From the Research

GLP-1 and Constipation

• GLP-1 receptor agonists have been associated with gastrointestinal adverse events, including constipation 3.
• A cross-sectional analysis of the National Institutes of Health All of Us Cohort found that constipation was a common GI adverse event among GLP-1 RA users, with a prevalence of 30.4% 3.
• The study also found that dulaglutide and liraglutide had higher rates of constipation compared to semaglutide and exenatide 3.
• Another study found that GLP-1 slows gastrointestinal motility, which can lead to constipation 4.
• However, it's worth noting that the effect of GLP-1 on gastrointestinal motility can vary depending on the specific GLP-1 receptor agonist used, as well as individual patient factors 5, 6.

Gastrointestinal Adverse Events

• GLP-1 receptor agonists have been associated with a range of gastrointestinal adverse events, including abdominal pain, diarrhea, nausea, vomiting, and pancreatitis 3, 7.
• The frequency and severity of these adverse events can vary depending on the specific GLP-1 receptor agonist used, as well as individual patient factors 4, 6.
• Some studies have found that certain GLP-1 receptor agonists, such as exenatide, may have a higher risk of gastrointestinal adverse events compared to others, such as semaglutide 3, 7.

Clinical Implications

• The association between GLP-1 receptor agonists and constipation, as well as other gastrointestinal adverse events, has important clinical implications 5, 4.
• Healthcare providers should carefully consider the potential risks and benefits of GLP-1 receptor agonists when prescribing them to patients, particularly those with a history of gastrointestinal disorders 6, 3.
• Patients should be closely monitored for gastrointestinal adverse events, and alternative treatments should be considered if these events occur 7.