Rhabdomyolysis: An Adverse Effect of Semaglutide?

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained widespread use in the management of type 2 diabetes mellitus and obesity due to their glucose-lowering effects, appetite suppression, and cardiovascular benefits. Despite a generally favorable safety profile, rare adverse events can occur. Musculoskeletal side effects are infrequently reported, and there are only two prior reported cases of rhabdomyolysis. This report aims to describe a new case of rhabdomyolysis potentially related to semaglutide. Case Description: 26 years old female presented to her primary care doctor’s office with pain in her arms. Her past medical history was significant for obesity. She followed an active lifestyle and workup routine that included weight lifting. However, this time the pain felt different than the typical muscle aches that she had had in the past. She started taking Semaglutide for weight loss 4 weeks prior to the onset of her symptoms. Outpatient blood work revealed a creatinine kinase (CK) of 6000 U/L and she was referred to the emergency department for further evaluation. A repeated CK was 10261 U/L, and a serum Creatinine (sCr) of 0.96 mg/dL. She was treated with intravenous isotonic solutions and Semaglutide was discontinued. She had a progressive resolution of her symptoms along with decreased CK to 4630 U/L and sCr to 0.75 mg/dL. Discussion: Rhabdomyolysis is a serious syndrome characterized by muscle breakdown and release of intracellular contents into the bloodstream. Common causes include trauma, prolonged immobilization, strenuous exercise, infections, and certain medications. To date, only two published case have directly implicated GLP-1 RAs as a potential cause of rhabdomyolysis. Mechanistically, GLP-1 receptors are present in multiple tissues, including skeletal muscle. Although direct muscle toxicity is not an established property of GLP-1 RAs, the possibility of rare idiosyncratic reactions or indirect pathways (mitochondrial effects, electrolyte imbalances) cannot be excluded. Physicians should be alert to signs of muscle injury, especially in patients initiating or titrating semaglutide, when unexplained muscle symptoms or elevated CK levels arise. Maybe, we should consider routine CK screening or exertional restrictions while initiating or up titrating GLP-1 RAs.