Mikami-Saito Yasuko, Maekawa Masamitsu, Watanabe Masahiro, Hosaka Shinichiro, Takahashi Kei, Totsune Eriko, Arai-Ichinoi Natsuko, Kikuchi Atsuo, Kure Shigeo, Katagiri Hideki, Wada Yoichi
Department of Pediatrics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Int J Mol Sci. 2025 Mar 25;26(7):2962. doi: 10.3390/ijms26072962.
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 (/ 423.24) in the urine exclusively during the oral administration of semaglutide. The MS/MS spectra at / 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.
肉碱在维持能量平衡和代谢灵活性方面起着至关重要的作用。多种药物，如与特戊酸结合的抗生素、丙戊酸和抗癌药物，可导致肉碱缺乏，抑制脂肪酸的利用，并促使低血糖的发生。尚无研究将口服司美格鲁肽与肉碱缺乏联系起来。在此，我们报告一例34岁男性患者，患有多种酰基辅酶A脱氢酶缺乏症，其肉碱缺乏归因于口服司美格鲁肽中的水杨丙嗪酸钠（SNAC）。该患者32岁时被诊断为2型糖尿病，接受司美格鲁肽注射治疗。改用口服司美格鲁肽后出现低血糖症状，游离肉碱平均水平显著下降。液相色谱-串联质谱分析显示，仅在口服司美格鲁肽期间，尿液中出现一个与SNAC-肉碱复合物相对应的峰（/423.24）。/423.24处的MS/MS谱图包含与SNAC和肉碱产物离子一致的峰。我们的结果表明，SNAC可能通过与肉碱络合而导致肉碱缺乏。医疗服务提供者在给高危个体使用含SNAC的药物时应监测肉碱缺乏情况。此外，该病例可能会引发对SNAC等药物赋形剂对代谢途径潜在影响的更多重大关注。
