Valproate intoxication in a patient with bipolar I disorder due to SGLT2 inhibitor-induced weight reduction

Introduction: Sodium glucose cotransporter 2 (SGLT2) inhibitors are hypoglycemic agents characterized by a weight loss effect. This effect is likely to increase blood levels of other drugs. Reason for the report: SGLT2 inhibitor-induced weight reduction could bring unexpected side effects of other drugs whose blood concentrations are affected by body weight. However, this interaction between SGLT2 inhibitor and other drugs via weight loss effect has not been reported so far. Case summary: I describe the case of a 67-year-old male with bipolar I disorder who was treated with valproate. He was diagnosed with type 2 diabetes mellitus, started treatment with empagliflozin, and his body weight decreased gradually. Two months after he started empagliflozin, he developed hand tremor which was one of the symptoms of valproate intoxication, and his tremor was improved by dose reduction of valproate. It seemed that this symptom was brought mainly by weight loss effect of empagliflozin. These observations suggest the existence of a detour where blood concentrations of some drugs are increased by weight loss due to SGLT2 inhibitors. Clinicians need to be aware of the blood levels of drugs in patients with type 2 diabetes mellitus after starting SGLT2 inhibitors. Graphical abstract