Can semaglutide (glucagon-like peptide-1 receptor agonist) cause severe fatigue?

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Last updated: June 30, 2025View editorial policy

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From the Guidelines

Semaglutide can cause severe fatigue in some patients, as indicated by the common side effects listed in the study published in 2023 1. The study outlines the mechanism of action, contraindications, and common side effects of semaglutide, a glucagon-like peptide-1 receptor agonist, which includes fatigue among other side effects like nausea, vomiting, diarrhea, and headache. Some key points to consider when evaluating the potential for semaglutide to cause severe fatigue include:

  • The medication's effect on glucose metabolism and potential for electrolyte imbalances
  • Reduced caloric intake leading to energy deficits
  • The medication's impact on the central nervous system
  • The importance of proper injection techniques and adherence to the prescribed dosing schedule for injectable forms
  • The need for patients to consult their healthcare provider if experiencing severe fatigue, rather than discontinuing the medication abruptly. As noted in the study, semaglutide is indicated for chronic weight management in adults without type 2 diabetes, as well as for adults with type 2 diabetes, with specific dosing recommendations and precautions, including monitoring for pancreatitis and use caution in patients with a history of pancreatitis or cholelithiasis 1. Given the potential for severe fatigue, healthcare providers should closely monitor patients taking semaglutide and adjust treatment as needed to minimize this and other side effects, while also considering the medication's benefits for weight management and glycemic control.

From the Research

Semaglutide and Fatigue

  • Semaglutide, a glucagon-like peptide-1 receptor agonist, is used to treat type 2 diabetes and aid in weight loss.
  • While semaglutide has been shown to have a favorable risk/benefit profile for patients with type 2 diabetes, with benefits including improved glycemic control and weight loss 2, its potential to cause severe fatigue is not well-documented in the majority of the studies.
  • Most studies have reported mild-to-moderate and transient gastrointestinal disturbances as the most common adverse events associated with semaglutide, with no mention of severe fatigue as a common side effect 2, 3, 4.
  • However, a case report suggests that semaglutide may contribute to muscle mass loss and subsequent fatigue, particularly in older adults 5.
  • This case report highlights the potential for semaglutide to cause sarcopenia, a condition characterized by age-related loss of muscle mass and strength, which can lead to fatigue 5.
  • Another study reported that nausea and diarrhea were the most common adverse events with semaglutide, but these were typically transient and mild-to-moderate in severity and subsided with time, with no mention of severe fatigue 4.
  • A review of the SUSTAIN 1-7 trials, which evaluated the efficacy and safety of semaglutide in over 8000 patients with type 2 diabetes, did not mention severe fatigue as a common side effect 6.

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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