Action Profile of Cobalt(III)-Insulin: A Novel Principle of Protraction of Potential Use for Basal Insulin Delivery

The Co₃₊-insulin hexamer is an extraordinary stable insulin hexamer that has no affinity for the insulin receptor per se but is converted into active insulin in vivo. In the present study, we evaluated the action profile of Co₃₊-insulin after subcutaneous injection into nondiabetic pigs and showed that the Co₃₊-hexamer does not dissociate before absorption. After absorption, Co₃₊-insulin is accumulated in the bloodstream because the complex is distributed and eliminated more slowly than human insulin. The degree of protraction of Co₃₊-insulin is similar to that of NPH insulin when evaluated in an euglycemic glucose clamp. We suggest that the long plasma half-life and a gradual in vivo activation contribute to prolong the effect of Co₃₊-insulin. The Co₃₊-insulin hexamer provides a novel principle of protraction of potential use for basal insulin delivery to the diabetic patient.