Potential Ketoacidosis Linked to Imeglimin and Metformin Co-administration in a Patient With Type 2 Diabetes

A 74-year-old woman with type 2 diabetes mellitus developed ketoacidosis within six days of adding metformin to imeglimin treatment. The patient was insulin-sensitive and showed preserved insulin secretion; therefore, insulin insufficiency alone was unlikely to contribute to the development of ketoacidosis. Both imeglimin and metformin partially inhibit complex I in the mitochondrial respiratory chain. Inhibition of mitochondrial respiration can lead to tricarboxylic acid (TCA) cycle suppression. Thus, the entry of acetyl-coenzyme A into TCA cycle is restricted, and it is eventually used in ketogenesis. Therefore, the combination of imeglimin and metformin might have precipitated the development of ketoacidosis.