New-Onset Autoantibody-Negative Diabetes With DKA Following Lorlatinib Therapy for ALK-Positive NSCLC

Lorlatinib, a tyrosine kinase inhibitor used in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), is associated with adverse events, including hyperglycemia. We present a case of a 52-year-old male with stage IV NSCLC and brain metastases who developed diabetic ketoacidosis (DKA) following lorlatinib initiation. The patient, without prior diabetes, presented with hyperglycemia (792 mg/dL), metabolic acidosis, and ketonuria 2 months after starting lorlatinib. He was treated for DKA and subsequently transitioned to a basal-bolus insulin regimen. Lorlatinib was withheld transiently and restarted once acute symptoms resolved. This case, along with three reported cases of lorlatinib-induced hyperglycemia, highlights a rare but serious potential complication. The mechanism of lorlatinib-induced hyperglycemia is unclear but may involve reduced insulin secretion. This case underscores the importance of monitoring for hyperglycemia in patients receiving lorlatinib, even in the absence of pre-existing diabetes, to enable early detection and prevent life-threatening complications like DKA.