GLP-1 Receptor Agonists and Adverse Effects

Gastrointestinal and Cardiovascular Effects

Nausea, vomiting, and diarrhea are the most frequently reported adverse effects of GLP-1 receptor agonists, occurring in a dose-dependent manner and more commonly with short-acting agents 1
Delayed gastric emptying can lead to gastrointestinal symptoms 2
GLP-1 receptor agonists increase heart rate by 3-10 beats per minute 2
Systolic blood pressure decreases by 2-3 mm Hg 2
Rare acute pancreatitis is a potential adverse effect of GLP-1 receptor agonists 1
There is a potential increased risk of cholelithiasis associated with GLP-1 receptor agonists 2

The American Diabetes Association and European Association for the Study of Diabetes consensus report describes GLP-1 receptor agonist safety profiles without any reference to fatigue as an adverse effect 3
The American Heart Association and Heart Failure Society of America scientific statement details cardiovascular and metabolic effects but does not list fatigue among the adverse effects 2

When a patient on a GLP-1 receptor agonist reports fatigue, hypoglycemia should be considered as a potential cause, especially when combined with sulfonylureas, as the risk increases 50% 3
Dehydration related to gastrointestinal side effects (nausea, vomiting, diarrhea) can also contribute to fatigue 1
Weight loss effects of GLP-1 receptor agonists can sometimes be associated with fatigue 3
Underlying diabetes complications, such as anemia from vitamin B12 deficiency or other diabetes-related conditions, should be investigated as potential causes of fatigue 3
The increase in heart rate caused by GLP-1 receptor agonists could theoretically contribute to fatigue in susceptible individuals 2