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, we developed a new self-administrable and minimally-invasive transdermal drug delivery strategy for home-based long-term treatment of obesity and other diseases. Specifically, ultrathin, core-shelled, and lance-shaped polymeric drug-reservoirs (micro-lances -MLs) were 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, we show that 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