The maintenance of glycemic control is most conveniently achieved using insulin pumps which require an insulin formulation that is stable for extended periods of time at body temperature. Current insulin formulations are only stable for days before chemical degradation and/or fibrillation results in loss of activity and the potential for clogging of insulin pumps. We have demonstrated the use of Cap-ClipTM technology for the rapid SAR discovery of conformation locked ultra-stable and ultra-concentrated insulins. Novel insulin analogues with both long acting and short acting profiles were discovered that are stable at 40⁰C for more than 3 months and can be concentrated to U1000 and greater. I will provide a summary of the discovery program and a preliminary SAR tree relating design principles to activity and stability.