Abstract: | Obesity is a serious epidemic health problem that can cause many other diseases including type 2 diabetes and cardiovascular diseases. Current approaches to combat obesity suffer from low effectiveness and adverse side effects. Here, a new self‐administrable and minimally invasive transdermal drug delivery strategy for home‐based long‐term treatment of obesity and other diseases is developed. Specifically, ultrathin, core‐shelled, and lance‐shaped polymeric drug reservoirs (micro‐lances [MLs]) are readily fabricated by a thermal pressing molding method and totally implanted into subcutaneous fat by lancing through the skin. Using a diet‐induced obese mouse model, it is shown that the development of obesity and associated metabolic disorders is effectively inhibited by applying therapeutic core‐shelled MLs once every 2 weeks. The outstanding therapeutic effects are attributable to highly localized and biphasic drug release, as well as combination therapy based on browning transformation of white fat and enhanced insulin sensitivity. |