Falsely elevated urinary C-peptide during angiotensin receptor–neprilysin inhibitor therapy: A case report

Background Urinary C-peptide testing is widely used to evaluate insulin secretion capacity from pancreatic β-cells. We report a case in which urinary C-peptide showed abnormally high levels during treatment with an angiotensin receptor–neprilysin inhibitor (ARNI). Case presentation The patient was a 54-year-old man undergoing treatment for type 2 diabetes mellitus and hypertension. Following an abnormal electrocardiogram during a health check-up, he was diagnosed with aortic valve insufficiency. During admission to the diabetes and endocrinology department for preoperative glycemic control, a clinical laboratory technologist first recognized a marked discrepancy between urinary and serum C-peptide results and reported this to the attending physician, prompting further investigation. A literature review revealed reports suggesting that ARNI administration may suppress C-peptide metabolism, potentially leading to elevation of measured values. Results The patient’s excreted urinary C-peptide level decreased markedly after ARNI therapy was discontinued, suggesting that ARNI influences an increase in urinary C-peptide. Conclusions When excreted urinary C-peptide is abnormally elevated and discrepant from the serum C-peptide level, it is important to confirm ARNI use and follow laboratory-driven recommendations for retesting after discontinuation if needed. Prompt reporting of this finding by the clinical laboratory is essential for the accurate assessment of insulin secretion capacity.