Long‐Acting Insulin‐Zwitterionic Polymer Conjugate Mitigates Hypoglycemia

Insulin, a main medication to control glycemia of type 1 and advanced type 2 diabetes, faces problems of a short half-life and poor stability during its clinical use. Zwitterionic polymer shows unique properties of antifouling and low immunogenicity. Here, we have synthesized a new insulin-zwitterionic polymer conjugate (INS-PMPC) through grafting-from strategy by controlled radical polymerization. Apart from showing excellent stability upon mechanical agitation, the resulting INS-PMPC conjugate provided over 20 h of glycemic control due to improved pharmacokinetics in diabetic mice with one single subcutaneous injection. Most importantly, this insulin-zwitterionic polymer conjugate significantly decreases the incidence of hypoglycemia.