The Neuroendocrine Effects of Pioglitazone in Patients With Cancer and Cachexia

Inclusion Criteria: * Age ≥18 years * Documented histologic or cytologic diagnosis of non-small-cell lung cancer or gastrointestinal cancer that is locally advanced and inoperable or metastatic (e.g., spread to distant organs) * Cachexia defined by Fearon criteria * Insulin resistance syndrome, defined with the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) * Ability to provide written informed consent, willing and able to comply with all scheduled visits, treatment plans, laboratory tests, and other study procedures * Provide written approval by a qualified healthcare professional * Allow the collection and storage of biospecimens and data for future use Exclusion Criteria: * Prior diagnosis of type 2 diabetes * Prior or current thiazolidinedione (TZD) therapy * Known hypersensitivity to TZD * New York Heart Association (NYHA) class I-IV heart failure * History of or actively treated bladder cancer * Current use of CYP2C inhibitor (e.g., gemfibrozil) or CYP2C inducer (e.g., rifampin) * Inadequate hepatic function * Currently pregnant, breastfeeding, or planning to become pregnant within the next 16 weeks * Contraindications to magnetic resonance imaging (e.g., implanted cardiac device, cochlear implant) * Any other condition that, in the investigator's opinion, would preclude participation or successful compliance with the protocol