Carnitine Deficiency Caused by Salcaprozic Acid Sodium Contained in Oral Semaglutide in a Patient with Multiple Acyl-CoA Dehydrogenase Deficiency

Abstract

Carnitine plays an essential role in maintaining energy homeostasis and metabolic flexibility. Various medications, such as pivalate-conjugated antibiotics, valproic acid, and anticancer agents, can induce carnitine deficiency, inhibit the utilization of fatty acid, and contribute to the development of hypoglycemia. No studies have linked oral semaglutide to carnitine deficiency. Herein, we report the case of a 34-year-old male patient with multiple acyl-CoA dehydrogenase deficiency who developed carnitine deficiency attributable to salcaprozic acid sodium (SNAC) in oral semaglutide. The patient was diagnosed with type 2 diabetes mellitus at 32 years of age and was treated with semaglutide injections. Hypoglycemic symptoms appeared after switching to oral semaglutide, and the mean levels of blood-free carnitine significantly decreased. Liquid chromatography-tandem mass spectrometry analysis revealed a peak corresponding to the SNAC-carnitine complex (m/z 423.24) in the urine exclusively during the oral administration of semaglutide. The MS/MS spectra at m/z 423.24 contained peaks consistent with those of the SNAC and carnitine product ions. Our results suggest that through complexation with carnitine, SNAC may induce carnitine deficiency. Healthcare providers should monitor for carnitine deficiency when administering SNAC-containing medications to at-risk individuals. Furthermore, this case can raise more significant concerns about the potential impact of pharmaceutical excipients like SNAC on metabolic pathways.

Keywords: carnitine deficiency; multiple acyl-CoA dehydrogenase deficiency; oral semaglutide; salcaprozic acid sodium; type 2 diabetes.

Figure 1

Chemical structures of (a) carnitine, (b) salcaprozic acid sodium (SNAC), and (c) SNAC–carnitine complex.

Figure 2

(a) MS spectra of m/z 420–430 in the urine during the period of oral semaglutide administration. (b) The chromatogram of m/z is 423.24. (c) MS/MS spectra of m/z 423.24, corresponding to the molecular weight of the SNAC–carnitine complex. The closed arrows indicate the product ions of SNAC, and the open arrows indicate those of carnitine.