Methods of reducing hypoglycemic episodes in the treatment of diabetes mellitus

The present invention provides compositions and methods for reducing hypoglycemic episodes experienced by a subject in need of treatment for diabetes mellitus, said method comprising orally administering an amount of an insulin polypeptide-oligomer conjugate to the subject, wherein: i) the amount of the insulin polypeptide-oligomer conjugate reduces the number and/or severity of hypoglycemic episodes experienced by the subject during a given time period when compared with the number and/or severity of hypoglycemic episodes that would have been experienced during a similar time period by the subject or by subjects in a control group parenterally administered insulin or an insulin analog in an amount that provides a substantially equivalent level of glycemic control; and ii) the oligomer of the insulin polypeptide-oligomer conjugate comprises a hydrophilic moiety and a lipophilic moiety.