It shows that significant hyperglycemia occurs in a substantial proportion of patients receiving PI3K or AKT inhibitors; that it is particularly likely in patients with baseline diabetes, pre‐diabetes, or elevated BMI that it is manageable with dose interruption, dose modification and/or pharmacologic management; and that SGLT2 inhibitors are a promising second‐line option after metformin, provided that all steps are taken to mitigate the potential risk of euglycemic D. The gene discussed is PIK3CA; the disease is diabetes mellitus.