Publisher Summary This chapter discusses insulin, glucagon, and oral hypoglycemic drugs and their adverse effects. With the increase in intensive therapy the attention devoted to hypoglycemia and the number of studies reporting on hypoglycemia has increased considerably. Insulin antibodies are often induced by animal insulins, which differ in 1 or 4 amino acids from human insulin. Insulin aggregates, found in long-acting insulins such as NPH and insulin zinc suspensions, also contribute to continued antibody formation. Even human insulin induces antibodies, although the titers are often lower than when using animal insulin. Insulin antibodies may further reduce the low incipient levels of free insulin after injection and may increase the half-life of (free) insulin. Subcutaneous (multiple) insulin injections remain a less-than perfect way to substitute for the defective betacell. To improve the regulation of blood glucose and diminish the burden of the injections, three major possibilities exist at present—namely, the use of the insulin pump or the (disposable) pen for multiple injections; the use of insulin analogs with specific changes in one or more of the amino acids, resulting in decreased polymerization or changes in absorption or breakdown; and other routes of administration of insulin.