Weight loss agents include compounds defined by Formula I or a pharmaceutically acceptable salt or prodrug thereof, compositions containing the same, and methods of use thereof are described herein. In some embodiments, the compound is Withaferin A. In other embodiments, the compound is Michael addition product of Withaferin A. The compounds can be administered to induce weight loss in a pre-obese, obese, or morbidly obese patient, reduce body fat in a pre-obese, obese, or morbidly obese patient, reduce food intake in a pre-obese, obese, or morbidly obese patient, improve glucose homeostasis in a pre-obese, obese, or morbidly obese patient, or combinations thereof.