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Because of its prolonged action, subcutaneously administered insulin has a potential for overcorrection hypoglycemia during closed-loop glucose control. For this reason, we hypothesized that subcutaneous glucagon, whose action is faster, could lessen the risk for hypoglycemia during closed-loop control. We therefore compared insulin alone versus insulin plus glucagon in diabetic rats in a controlled closed-loop study. Both hormones were delivered by algorithms based on proportional error, derivative error, and the glucose history. Based on this algorithm, glucagon was delivered when glucose was declining and approaching a hypoglycemic level. The delivery of glucagon was largely reciprocal with the delivery of insulin. With the addition of glucagon, there was less hypoglycemia at the glucose nadir, less hyperglycemia later in the study, and lower absolute error values during these periods. We also found that for 7 days after glucagon reconstitution, commercially available glucagon retained its original ability to quickly raise glucose level. We conclude that when subcutaneous insulin delivery is accompanied by subcutaneous glucagon, glycemic control during closed-loop treatment is improved. Since its action is faster than that of insulin, glucagon may prove useful during closed-loop diabetes control.