S5687 Hepatotoxicity Linked to Compounded Semaglutide: A Rare Case of Probable Drug-Induced Liver Injury

Introduction: Semaglutide, a glucagon-like peptide-1 (GLP-1) has been shown to improve liver enzymes with metabolic dysfunction associated steatotic liver disease (MASLD) and metabolic dysfunction associated steatohepatitis (MASH). Semaglutide-induced liver injury is rarely reported. We present a rare case of probable drug induced liver injury (DILI) associated with compounded semaglutide. Case Description/Methods: A 58-year-old man was referred to hepatology clinic for incidentally detected elevation in liver chemistries. Due to insurance limitations on coverage of weight-loss medications, the patient had procured compounded semaglutide from a direct-to-consumer telehealth platform. He administered increasing weekly doses (10 mg, 20 mg, 30 mg, and 40 mg) over a 4-week period. Approximately 1 week after the last dose, routine laboratory workup revealed significant elevations in liver enzymes consistent with hepatocellular injury: aspartate aminotransferase 1,184 U/L, alanine aminotransferase 944 U/L, alkaline phosphatase 261 U/L, and total bilirubin 2.3 mg/dl. The patient discontinued the medication thereafter. He was asymptomatic throughout and there was no concurrent illness, shock, or heart failure. He denied alcohol use, herbal or over-the-counter supplement intake. Extensive workup excluded viral, autoimmune, and obstructive etiologies. Following drug cessation, liver enzymes progressively normalized over the next 2 months. Discussion: Semaglutide was deemed the probable cause of DILI in our patient, supported by a Roussel Uclaf Causality Assessment Method score of 8, temporal correlation with drug initiation, resolution upon withdrawal, and absence of alternative etiologies. The exact cause of semaglutide-induced liver injury remains unclear. While semaglutide has been linked to liver stress from rapid weight loss and biliary disease in previous case reports, our patient lacked these risk factors. Notably, our patient had been using compounded semaglutide—an unregulated formulation often accessible without a prescription through online platforms, prepared with semaglutide base or acetate instead of the Food and Drug Administration-approved sodium salt, and potentially containing variable excipients that can affect bioavailability, metabolism, and toxicity. This case underscores importance of clinician vigilance and routine liver function monitoring in patients using compounded semaglutide as this poses a potential health threat to patients.