The physiological rationale for oral insulin administration.

Insulin remains the most effective and durable drug in the armamentarium for the treatment of advanced-stage diabetes. Nevertheless, clinical studies have shown that even on insulin treatment, a significant percentage of patients fail to attain lasting glycemic control. Well-recognized reasons for this failure include issues related to patients' noncompliance with an injectable drug and the late stage at which insulin is prescribed, but less explicit reasons related to the nonphysiological way insulin is currently administered are equally important. Parenteral insulin targets peripheral tissue rather than the liver with pharmacokinetics that do not replicate the normal dynamics of endogenous insulin release. Oral insulin is one of several alternative methods of insulin administration that are in clinical stages of development. The oral route of insulin delivery takes advantage of the portal-hepatic route of absorption. A review of relevant physiology is herewith provided.