Objective: To present 2 cases in which patients previously diagnosed with type 2 diabetes (T2D) rapidly progressed to insulin dependence following cancer treatment with immune checkpoint inhibitors (ICH). Both patients were subsequently found to be positive for glutamic acid decarboxylase 65 antibodies (+GAD), indicative of type 1.5 diabetes (T1.5D). Methods: Patient history, laboratory results, and treatment course, in addition to review of the relevant literature, are presented. Results: The first case involved a 78-year-old man with lung cancer and a 30-year history of T2D (controlled with oral medications [OM]) who developed polydipsia, polyuria, and nocturia 5 weeks post-treatment with nivolumab. Basal bolus insulin was required, and frequent insulin increments were necessary to achieve metabolic control. The patient had no personal or family history of autoimmunity. The second case involved a 55-yearold man with metastatic melanoma and a 4-year history of T2D who required transition from OM to basal bolus insulin following treatment with ipilimumab. Hypophysitis prompted discontinuation of ipilimumab and initiation of pembrolizumab, which was followed by the need for an intensive escalation of insulin dosage for glucose control.