Lifestyle-related type 2 diabetes and associated obesity (diabesity) affect >2.5 billion people worldwide and impose nearly $3 trillion in annual health care costs. We developed an implantable, wirelessly powered electrocatalytic closed-loop health optimization (ECHO) device containing platinum-decorated gold nanoclusters embedded in graphite felt that enabled selective, electrically tunable oxidation of blood glucose to renally cleared gluconate. In type 2 diabetic mice, wireless, low-power activation (0.75 volts, 10 milliamperes) restored glucose homeostasis within 1 hour, shifted metabolism from glucose to lipid utilization, reduced body weight and triglycerides, and increased circulating free fatty acids and ketone bodies without detectable hypoglycemia or adverse physiological, inflammatory, or behavioral effects during 6 weeks of treatment. Coupling this ECHO device to a commercial continuous glucose monitoring system enabled autonomous, smartphone-controlled, drug-free closed-loop management of experimental diabesity.