From the Guidelines
GLP-1 medications are generally safe for most patients when prescribed appropriately, and their benefits often outweigh the temporary gastrointestinal side effects, which can be minimized with proper dose escalation and lifestyle adjustments. These medications, such as semaglutide (Ozempic, Wegovy), liraglutide (Victoza, Saxenda), and tirzepatide (Mounjaro), work by mimicking a hormone that regulates blood sugar and appetite, but they commonly cause nausea, vomiting, diarrhea, or constipation, especially when first starting treatment or increasing doses 1. According to a recent study published in Anaesthesia, the most frequently reported adverse effects of GLP-1 receptor agonists are nausea, vomiting, and diarrhea, which are dose-dependent and more frequent with short-acting drugs 1.
To minimize side effects, patients should follow the prescribed gradual dose escalation schedule, eat smaller meals, avoid fatty foods, stay hydrated, and take the medication consistently, as recommended by the kdigo 2020 clinical practice guideline for diabetes management in chronic kidney disease 1. The guideline suggests starting with a low dose of GLP-1 RA and titrating up slowly to minimize gastrointestinal side effects. Some key points to consider when prescribing GLP-1 medications include:
- Starting with a low dose and titrating up slowly to minimize gastrointestinal side effects
- Eating smaller meals and avoiding fatty foods to reduce the risk of nausea and vomiting
- Staying hydrated to prevent dehydration and electrolyte imbalances
- Taking the medication consistently to maintain its therapeutic effects
The benefits of GLP-1 medications for diabetes management and weight loss often outweigh these temporary discomforts for most patients, as they have been shown to improve cardiovascular outcomes and reduce the risk of major adverse cardiovascular events, as demonstrated by the LEADER trial and the SUSTAIN 6 trial 1. As an NP, you can explain that while these medications aren't perfect, they're well-studied with established safety profiles when used appropriately, and their benefits can be optimized with proper patient education and monitoring.
From the FDA Drug Label
Gastrointestinal: Acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death, ileus Gastrointestinal: ileus The delay in gastric emptying is dose-dependent but is attenuated with the recommended dose escalation to higher doses of TRULICITY
The GLP-1 receptor agonists, such as liraglutide and dulaglutide, may cause gastrointestinal adverse reactions, including:
- Acute pancreatitis
- Ileus Additionally, these medications can delay gastric emptying, which may affect the absorption of concomitantly administered oral medications. 2 3
From the Research
GLP-1 Receptor Agonists and Gastrointestinal Side Effects
- GLP-1 receptor agonists are known to cause gastrointestinal side effects, including nausea, vomiting, diarrhea, and abdominal pain 4, 5, 6, 7.
- These side effects are thought to be related to the delayed gastric emptying caused by GLP-1 receptor agonists 8, 4.
- The risk of gastrointestinal side effects varies among different GLP-1 receptor agonists, with semaglutide having the greatest risk of nausea, diarrhea, vomiting, and constipation 7.
- Liraglutide has been associated with a higher risk of abdominal pain and pancreatitis compared to other GLP-1 receptor agonists 7.
- Most gastrointestinal side effects tend to occur within one month of starting treatment with GLP-1 receptor agonists 7.
Comparison of GLP-1 Receptor Agonists
- Different GLP-1 receptor agonists have varying effects on glycemic control, weight loss, and gastrointestinal side effects 8, 5.
- Short-acting GLP-1 receptor agonists, such as exenatide, have a greater effect on postprandial glucose levels, while long-acting agents, such as liraglutide and semaglutide, have a more profound effect on overnight and fasting plasma glucose 8.
- The choice of GLP-1 receptor agonist should be individualized based on patient characteristics, clinical profile, and patient preference 5.
Gastrointestinal Side Effects and GLP-1 Receptor Agonists
- Gastrointestinal side effects are a common adverse event associated with GLP-1 receptor agonists, with a median age of 62 years old 7.
- The severe proportion of GLP-1 receptor agonist-associated gastrointestinal adverse events varies among different agents, with liraglutide having the highest severe rate 7.
- GLP-1 receptor agonists have been associated with an increased risk of gastrointestinal system disorders, including gastroesophageal reflux disease, gastritis, and pancreatitis 7.