What are the principal gastrointestinal effects of Glucagon-Like Peptide-1 (GLP-1) agonists?

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From the Guidelines

The principal gastrointestinal effects of Glucagon-Like Peptide-1 (GLP-1) agonists include nausea, vomiting, diarrhea, and delayed gastric emptying, which can be managed by starting with a low dose and gradually increasing it, as well as staying well-hydrated and eating smaller, more frequent meals 1. The gastrointestinal effects of GLP-1 agonists are dose-dependent and more frequent with short-acting than long-acting drugs.

  • Nausea and vomiting are the most common adverse effects, which can be avoided in patients with gastroparesis by not using GLP-1 receptor agonists.
  • Dyspepsia can be managed by starting GLP-1 receptor agonists at a low dose and titrating upward slowly.
  • Diarrhea can be reduced by decreasing meal size.
  • Gastrointestinal reflux can be limited by avoiding alcohol and carbonated drinks.
  • Constipation can be avoided by not consuming a high-fat diet. Some studies have also reported a risk of pancreatitis associated with the use of GLP-1 agonists, although the relationship is not clear 1. The delayed gastric emptying caused by GLP-1 agonists can lead to gastroparesis, which is a key mechanism behind both their therapeutic benefits and side effects. It is essential to weigh the benefits and risks of using GLP-1 agonists, particularly in patients with a history of pancreatitis or those at high risk for cardiovascular events 1. In the peri-operative period, there are concerns that the use of GLP-1 receptor agonists is associated with an increased risk of bronchopulmonary aspiration due to retained gastric contents, and the minimum cessation period required for these drugs is currently unknown 1. However, the current evidence suggests that GLP-1 agonists can be continued throughout the peri-operative period, but with careful monitoring and management of potential gastrointestinal side effects 1.

From the FDA Drug Label

Gastrointestinal: ileus Gastrointestinal: Acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death, ileus TRULICITY delays gastric emptying and thus has the potential to reduce the rate of absorption of concomitantly administered oral medications.

The principal gastrointestinal effects of GLP-1 agonists are:

  • Delayed gastric emptying
  • Ileus
  • Acute pancreatitis (including hemorrhagic and necrotizing pancreatitis) These effects can lead to complications such as reduced absorption of oral medications, intestinal obstruction, and potentially life-threatening pancreatic damage 2 3.

From the Research

Principal Gastrointestinal Effects of GLP-1 Agonists

The principal gastrointestinal effects of Glucagon-Like Peptide-1 (GLP-1) agonists include:

  • Nausea, which is the most common gastrointestinal adverse event for all treatments 4
  • Abdominal pain, constipation, diarrhea, and nausea and vomiting, which are also common gastrointestinal adverse events 5
  • Retardation of gastric emptying, which reduces postprandial glycemia 6
  • Increased fasting and postprandial gastric volumes 6

Comparison of Gastrointestinal Effects Among Different GLP-1 Agonists

  • Exenatide once weekly has been shown to have fewer gastrointestinal adverse events compared to exenatide twice daily and liraglutide 4
  • Dulaglutide and liraglutide have higher rates of abdominal pain, constipation, diarrhea, and nausea and vomiting compared to semaglutide and exenatide 5
  • Liraglutide and exenatide have the highest rates of pancreatitis 5

Management of Gastrointestinal Side Effects

  • Gastrointestinal side effects can be managed with guidance from practitioners to optimize therapeutic outcomes with GLP-1RAs 7
  • Selection of the most appropriate treatment for individual patients is important, considering the differences in gastrointestinal effects among different GLP-1 agonists 8

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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