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

Semaglutide and Rhabdomyolysis: Clinical Evidence and Recommendations

Semaglutide can potentially cause rhabdomyolysis, although this appears to be a rare adverse effect that is not widely documented in major clinical guidelines but has been reported in case literature.

Evidence for Semaglutide-Associated Rhabdomyolysis

The most direct evidence comes from a 2023 case report describing a 47-year-old woman who developed myalgias, weakness, and elevated creatine kinase consistent with rhabdomyolysis while taking semaglutide for weight loss 1. Her symptoms resolved after discontinuation of semaglutide, but recurred upon rechallenge at a lower dose, with urinalysis confirming myoglobinuria. The symptoms again resolved rapidly after stopping the medication.

This case report is significant as it:

• Documents a clear temporal relationship between semaglutide use and rhabdomyolysis
• Shows symptom recurrence upon rechallenge (positive rechallenge)
• Demonstrates resolution upon discontinuation
• Appears to be the first documented case in medical literature

Safety Profile of Semaglutide in Guidelines

Major guidelines from the American Gastroenterological Association (2022) and American Diabetes Association (2023) do not specifically mention rhabdomyolysis as a known adverse effect of semaglutide 2. Instead, they focus on more common adverse effects:

• Gastrointestinal symptoms (nausea, vomiting, diarrhea)
• Increased risk of pancreatitis
• Gallbladder disease (cholelithiasis)
• Delayed gastric emptying

A comprehensive safety review of semaglutide published in Frontiers in Endocrinology (2021) also did not identify rhabdomyolysis as a recognized adverse effect 3.

Clinical Approach to Suspected Semaglutide-Induced Rhabdomyolysis

If rhabdomyolysis is suspected in a patient taking semaglutide:

1. Immediate assessment:

   • Check creatine kinase levels
   • Assess renal function (creatinine, BUN)
   • Perform urinalysis for myoglobinuria
   • Evaluate electrolytes, particularly potassium

2. Management considerations:

   • Consider discontinuation of semaglutide if rhabdomyolysis is confirmed
   • Provide aggressive IV hydration to prevent acute kidney injury
   • Monitor renal function and electrolytes closely
   • Treat any electrolyte abnormalities

3. Differential diagnosis:

   • Rule out other common causes of rhabdomyolysis:
     • Trauma or excessive exercise
     • Medications (statins, antipsychotics)
     • Infections
     • Metabolic disorders
     • Electrolyte abnormalities

Risk-Benefit Assessment

When considering semaglutide therapy, clinicians should weigh:

• Benefits: Significant weight loss, improved glycemic control, cardiovascular benefits, and renal protection 2, 4
• Common risks: Gastrointestinal side effects, gallbladder disease 2
• Rare risks: Potentially rhabdomyolysis, based on limited case evidence 1

Conclusion

While rhabdomyolysis associated with semaglutide appears to be rare based on current evidence, clinicians should maintain vigilance for muscle-related symptoms in patients taking this medication. The single case report suggests this may be specific to semaglutide rather than a class effect of GLP-1 receptor agonists 1. When such symptoms occur, prompt evaluation of creatine kinase levels and consideration of medication discontinuation is warranted.

Given the overall favorable risk-benefit profile of semaglutide for metabolic and cardiovascular outcomes, this rare potential adverse effect should not preclude its use in appropriate patients, but should be part of the monitoring considerations during therapy.