Abstract: Insulin was first isolated a century ago, yet commercial formulations of insulin for hormone replacement therapy fall short of mimicking the endogenous glycemic control that occurs in non-diabetic individuals. Moreover, diabetes management is increasingly relying on automated insulin delivery using closed-loop systems to improve glucose management and reduce patient burden. However, improvements in insulin formulations, sensors, and algorithms are required to shift from hybrid systems to fully autonomous delivery. Insulin formulations that better mimic secretion from the beta-cells, by enabling more rapid insulin absorption kinetics and/or co-delivering complementary hormones (i.e. amylin), would improve diabetes management. However, formulation innovation is complicated by the poor stability of insulin monomers and amylin. Here, I will discuss two polymeric excipient platforms (non-covalent PEGylation and amphiphilic copolymer excipients) that can be used to increase the stability of insulin in formulation and modulate insulin pharmacokinetics. Using these designer excipients, I have developed three insulin formulations: (i) an ultrafast monomeric insulin lispro, (ii) an insulin-amylin co-formulation and (iii) an ultrafast co-formulation. These enhanced insulin formulations are promising candidates to address formulation challenges related to achieving fully autonomous insulin delivery, improve glucose control, and reduce the burden of treatment management for patients with diabetes.