From the Guidelines
GLP-1 receptor agonists commonly cause diarrhea due to delayed gastric emptying, increased intestinal transit time, altered gut microbiota composition, and potential pancreatic enzyme insufficiency, as reported in a recent narrative review of clinical pharmacology and implications for peri-operative practice 1.
Causes of Diarrhea
The primary cause of diarrhea associated with GLP-1 receptor agonists is delayed gastric emptying, which disrupts normal digestive processes. Additionally, these medications increase intestinal transit time, causing food to move too quickly through the intestines, reducing water absorption and resulting in loose stools.
- Delayed gastric emptying: slows down the movement of food from the stomach to the intestines, disrupting normal digestion 1.
- Increased intestinal transit time: causes food to move too quickly through the intestines, reducing water absorption and resulting in loose stools.
- Altered gut microbiota composition: potentially contributes to digestive disturbances, as reported in studies on the effects of GLP-1 receptor agonists on the gut microbiome 1.
- Pancreatic enzyme insufficiency: leads to malabsorption and diarrhea in some patients.
Management Strategies
Management strategies for GLP-1 receptor agonist-induced diarrhea include:
- Starting with lower doses and gradually increasing, as with weekly semaglutide starting at 0.25mg and slowly titrating up 1.
- Staying well-hydrated to prevent dehydration.
- Avoiding trigger foods that can exacerbate diarrhea.
- Temporarily reducing the medication dose if symptoms are severe, as recommended in the management of adverse effects of GLP-1 receptor agonists 1. If diarrhea persists beyond 4-6 weeks at a stable dose or is particularly troublesome, patients should consult their healthcare provider for further evaluation, as suggested in the narrative review of clinical pharmacology and implications for peri-operative practice 1.
From the FDA Drug Label
Metabolism and nutrition: Dehydration resulting from nausea, vomiting and diarrhea The FDA drug label mentions diarrhea as a possible adverse reaction, but it does not directly state the causes of GLP-1 related diarrhea.
- The label mentions that dehydration can result from nausea, vomiting, and diarrhea.
- However, it does not provide information on the specific causes of GLP-1 related diarrhea. 2
From the Research
Causes of GLP-1 Related Diarrhea
- The use of GLP-1 receptor agonists has been associated with gastrointestinal adverse events, including diarrhea 3, 4, 5.
- A mixed treatment comparison meta-analysis found that all GLP-1 dose groups significantly increased the probability of diarrhea relative to placebo and conventional treatment 3.
- The study found a dose-dependent relationship of exenatide and liraglutide on gastrointestinal adverse events, including diarrhea 3.
- Liraglutide 1.2 mg once daily was found to have a higher risk of diarrhea compared to other GLP-1 receptor agonists 3.
- The exact mechanism of GLP-1 related diarrhea is not fully understood, but it is thought to be related to the delayed gastric emptying and slowed gastrointestinal motility caused by GLP-1 receptor agonists 6, 5.
- Gastrointestinal adverse events, including diarrhea, are common with GLP-1 receptor agonists, but are often transient and may decrease over time 6, 4, 5.