INS and hyperinsulinism: To address the reported hyperinsulinemia/hyperglycemia seen in clinical studies, tumor-naive, immunocompromised NSG and immunocompetent C57BL/6J mice were treated with modified paxalisib dosing regimens, alone and in combination with metformin (a commonly prescribed therapy for type 2 diabetes, used to control blood glucose), daily for 2-weeks (5 days on, 2 days off), and sacrificed 4 hours after final treatment to assess fasting blood glucose and C-peptide levels (surrogate measure of insulin levels).