Disclosed are a system, a device, processes, techniques and computer-readable media that set an insulin adjustment factor that is applied to a dose of a therapeutic exogenous substance. The adjustment factor accounts for production of endogenous insulin related to the therapeutic exogenous substance. A processor of an automatic drug delivery device may determine and administer the doses of the therapeutic exogenous substance according to a process in which an amount of a therapeutic exogenous substance to deliver is estimated. An insulin adjustment factor utilizing an estimated relative therapeutic exogenous substance concentration may be determined. The processor may calculate a compensating dose of the therapeutic exogenous substance based on the estimated amount of the therapeutic exogenous substance to deliver that is modified by the insulin adjustment factor. The compensating dose of the therapeutic exogenous substance may be expelled from a reservoir by a pump mechanism.