Abstract
BACKGROUND: Our case is the first report showing the development of hypoglycemia following the administration of vadadustat in a patient with chronic kidney disease being treated with mitiglinide and sitagliptin, possibly due to drug-drug interaction between vadadustat and sitagliptin under the administration of mitiglinide. CASE PRESENTATION: A 72-year-old man with type 2 diabetes mellitus had received sitagliptin 50 mg once daily and mitiglinide 10 mg three times daily over the last 3 years. He initiated vadadustat 300 mg once daily orally on day X owing to renal anemia (hemoglobin A1c: 7.4% and estimated glomerular filtration rate: 28.0 mL/min/1.73 m(2)). On day 23, he developed hypoglycemia with a blood glucose level of 67 mg/dL. The mean blood glucose level ± standard deviation was lower in the first 24 days of co-administration of vadadustat (before breakfast: 94 ± 14 mg/dL, before lunch: 109 ± 24 mg/dL, and before dinner: 126 ± 39 mg/dL) than in the last 2 weeks (before breakfast: 108 ± 14 mg/dL, before lunch: 122 ± 24 mg/dL, and before dinner: 158 ± 39 mg/dL). Considering the timing of the concomitant administration of vadadustat, hypoglycemia may have been caused by the drug-drug interaction between sitagliptin and vadadustat, and he discontinued treatment with vadadustat. The mean blood glucose levels improved two weeks after the discontinuation of vadadustat (before breakfast: 121 ± 25 mg/dL, before lunch: 147 ± 38 mg/dL, and before dinner: 161 ± 36 mg/dL). The drug interaction probability scale was classified as "Probable" (5 points). CONCLUSIONS: Hypoglycemia was observed when sitagliptin, mitiglinide, and vadadustat were concomitantly administered, which may have resulted in a drug-drug interaction between vadadustat and sitagliptin via OAT3 inhibition in the renal tubules.