S5603 Drug-Induced Liver Injury With Combination Semaglutide and Atorvastatin

Introduction: Semaglutide is a glucagon-like peptide 1 (GLP-1) agonist used for management of type 2 diabetes and obesity. Adverse effects include nausea, change in bowel pattern, and rare cases of pancreatitis. Drug induced liver injury (DILI) associated with semaglutide has not been frequently described. Atorvastatin is an HMG-CoA reductase inhibitor associated with mild aminotransferase elevations in a small number of patients. We report a case of liver injury related to semaglutide and concurrent statin use. Case Description/Methods: A 56-year-old woman with hypertension, hyperlipidemia, type 2 diabetes and hypothyroidism was referred to the Gastroenterology clinic for evaluation of elevated liver enzymes. Initial routine labs had a normal liver panel. Oral semaglutide 3 mg was started for her diabetes and increased to 7 mg a month later and changed from pravastatin 40 mg to atorvastatin 20 mg for persistent LDL elevation. Labs after 4 months showed elevation of alkaline phosphatase (ALP) to 352 U/L, aspartate aminotransferase (AST) to 43 U/L and alanine aminotransferase (ALT) to 61 U/L. After 2 weeks alkaline phosphatase (ALP) was 398 U/L, then 442 U/L after another 2 weeks. Hepatic ultrasound revealed increased hepatic echogenicity typical of steatosis. Her PCP advised her to discontinue semaglutide but continued atorvastatin. She denied personal or family history of liver disease. Her home medications include levothyroxine, losartan, metformin, and a multivitamin. She denied use of other supplements or alcohol. Workup by GI included a negative hepatitis panel, antinuclear antibody screen, antimitochondrial antibody, iron panel and ferritin, ceruloplasmin, alpha-1 antitrypsin, and celiac testing. Anti-smooth muscle antibody mildly elevated to 1:40 and gamma-glutamyl transferase (gamma-glutamyl transferase) was elevated to 349 U/L. She remained off semaglutide with repeat liver panel 2 months later showing aspartate aminotransferase 20 U/L, alanine aminotransferase 20 U/L, and ALP normalized to 129 U/L. Discussion: DILI associated with semaglutide is rare and though it has been well described, is uncommon with statins. Our patient had evidence of liver injury after starting semaglutide with a change of statin which improved after semaglutide was stopped despite continuation of atorvastatin. It is possible that induction of both medications concurrently caused DILI. Although rare, with the increasing popularity of GLP-1 agonists and widespread use of statins, clinicians should be aware of this potential effect and monitor hepatic function when prescribing these medications in combination.