TBE001-A-S033

Insulin is a potent medication for managing diabetes, yet its short half-life requires daily administration. Currently, Novo Nordisk's icodec is the sole insulin available on the market that requires administration only once a week. Insulin icodec, developed by Novo Nordisk through amino acid mutations and fatty acid side chain modifications, has demonstrated the capability to control blood glucose levels on a once-weekly basis. To improve its efficacy, we modified the acylation side chain of icodec to generate insulin analogs appropriate for weekly dosing. A promising insulin analog, TBE001-A-S033, was synthesized and conjugated, and its efficacy was assessed in ICR and db/db mice. TBE001-A-S033 prolonged blood glucose control in ICR mice and exhibited a comparable blood glucose trend to insulin icodec in db/db mice. These findings suggest that TBE001-A-S033 possesses a favorable hypoglycemic effect and a differential half-life across species compared to insulin icodec, indicating its potential for once-weekly use in humans. This preclinical investigation indicates that TBE001-A-S033 may serve as an effective therapeutic for type 2 diabetes mellitus (T2DM).