GLP-1 and GLP-1/GIP Medications Can Cause Fatigue
Yes, GLP-1 and GLP-1/GIP medications can cause fatigue, which is documented as an adverse effect in clinical guidelines and drug labeling. While not as commonly discussed as gastrointestinal side effects, fatigue is a recognized side effect that patients and clinicians should be aware of.
Evidence for Fatigue as an Adverse Effect
- FDA drug labeling for dulaglutide (Trulicity) specifically lists fatigue as an adverse reaction occurring in ≥5% of treated patients (5.6% for the 1.5 mg dose compared to 2.6% for placebo) 1
- Clinical guidelines note that very-low-calorie diets, which can mimic some metabolic effects of GLP-1 medications, are associated with "severe fatigue" as a potential complication 2
- In the FDA labeling, fatigue is categorized alongside asthenia and malaise, suggesting a spectrum of energy-related adverse effects 1
Mechanism of Fatigue with GLP-1/GIP Medications
Several physiological mechanisms may contribute to fatigue in patients taking these medications:
- Delayed gastric emptying, which is a well-documented effect of GLP-1 receptor agonists, may contribute to feelings of fullness, reduced nutrient absorption rate, and subsequent fatigue 2
- Rapid weight loss induced by these medications may temporarily lead to energy deficits and fatigue 2
- Central nervous system effects, as GLP-1 receptors are found in the brain including the hippocampus, neocortex, and cerebellum, potentially influencing energy perception 2
- Cardiovascular effects, as GLP-1 receptors are localized to the sinoatrial node and may influence heart rate and cardiac function 2
Management of Fatigue in Patients on GLP-1/GIP Medications
When fatigue occurs in patients taking GLP-1 or GLP-1/GIP medications, consider the following approach:
- Rule out other causes of fatigue such as hypoglycemia, especially in patients also taking insulin secretagogues 1
- Ensure adequate nutrition despite reduced appetite, focusing on protein and micronutrient intake 2
- Consider dose adjustment by starting at a lower dose and titrating more slowly to improve tolerability 2
- Monitor for electrolyte abnormalities, which can accompany rapid weight loss and contribute to fatigue 2
- Evaluate for other side effects that may contribute to fatigue, such as gastrointestinal symptoms or sleep disturbances 2
Clinical Considerations and Caveats
- Fatigue may be more pronounced during the initial titration period and often improves with continued use 2
- The risk of fatigue should be weighed against the significant benefits of these medications for glycemic control, weight management, and cardiovascular outcomes 2
- Patients with pre-existing conditions causing fatigue (e.g., sleep apnea, heart failure) may experience compounded symptoms and require closer monitoring 2
- Fatigue may be more common with higher doses, as adverse effects are generally dose-dependent 2
Special Populations
- In patients with heart failure, caution is warranted as small trials have shown potential for increased cardiac events with liraglutide 2
- Elderly patients may be more susceptible to fatigue and related adverse effects 1
- Patients undergoing surgery should be monitored for fatigue as part of the overall risk assessment, particularly given concerns about delayed gastric emptying 2
By recognizing fatigue as a potential side effect and implementing appropriate management strategies, clinicians can help patients maintain adherence to these beneficial medications while minimizing impact on quality of life.