Apparatus and methods calculate and deliver doses of insulin and optionally glucagon into a subject. Online operation controls delivery of correction doses of insulin automatically in response to regular glucose measurements from a sensor, and offline operation calculates and delivers correction doses based on isolated glucose measurements and information gathered autonomously during preceding online operation. In another aspect, offline operation includes automatically calculating and administering meal doses based on information gathered autonomously during preceding periods of online operation. Both methods include generating relevant control parameters tailored to the individual and continually converged upon and potentially modulated during online operation. The control parameters are employed in real time during periods of offline operation to regulate glucose level without the need for user-provided control parameters such as correction factors and insulin-to-carbohydrate ratios.
