For individuals with diabetes at particularly high risk of dementia, such as carriers of APOE ε4 or individuals with a family history of dementia, it may be particularly beneficial to find ways to manage or mitigate gastrointestinal adverse effects (eg, switching to slower-release formulations of metformin or taking the medication with food in the evening)20 instead of replacing metformin with other agents given that participants in this study remained on antidiabetes drugs after early termination with metformin. This evidence concerns the gene APOE and diabetes mellitus.