The Role of GLP-1 Agonists in Mitigating Lorlatinib-Induced Metabolic Syndrome: Two Case Studies

• Lorlatinib-induced metabolic syndrome, including hypercholesterolemia, hypertriglyceridemia, weight gain, and hyperglycemia, poses a significant challenge during therapy. • Metabolic disturbances may not warrant lorlatinib dose reduction in mild to moderate cases, as they are often manageable with adjunctive therapies such as lipid-lowering agents. • Our cases demonstrate the potential of GLP-1 receptor agonists (e.g., semaglutide) to effectively address metabolic side effects, including weight loss and normalization of lipid and glycemic profiles. • A phase II clinical trial is warranted to rigorously evaluate the pharmacokinetics and safety of GLP-1 agonists in combination with lorlatinib, given their potential to enhance patient quality of life and long-term treatment adherence. • Oncologists should screen patients for metabolic syndrome prior to lorlatinib initiation and throughout treatment to enable early intervention and tailored treatment strategies.