The oral administration of insulin is difficult to achieve because the large peptide hormone is poorly absorbed and is subjected to enzymatic and acidic degradation in the stomach. Emisphere Technologies Inc is developing formulations of insulin co-administered with a drug delivery agent. With the proprietary Eligen technology employed, the carrier agent appears to form a conformational complex with insulin that can protect against degradation and facilitate the absorption of the hormone through the intestinal wall. In animal studies and phase I clinical trials, dosing with Eligen insulin led to a rapid elevation of plasma insulin and subsequent decrease in plasma glucose levels; the onset of activity was more rapid and insulin concentrations were higher with Eligen insulin than with injected insulin. Formulations of Eligen insulin have been well tolerated in all clinical trials performed to date. In a phase II clinical trial in patients with type 2 diabetes, Eligen insulin in combination with metformin failed to achieve significant superior glycemic control over treatment with metformin alone. Eligen oral insulin formulations may have potential as prandial insulin therapies in patients with either type 1 or type 2 diabetes; however, no clinical trials for such treatments appeared to be ongoing at the time of publication.