Rapidly Evolving Insulin Landscape: Ultrashort Acting and Ultralong Acting

Since the discovery of insulin in 1921, there has been remarkable evolution in insulin treatment for diabetes, with modern insulin analogues utilizing highly engineered recombinant technology. The purpose of this review is to focus on two revolutionary developments in contemporary insulin therapy: once-weekly ultralong-acting basal insulins and ultrashort-acting bolus insulins. Insulin icodec and insulin efsitora alfa represent a unique shift in basal insulin delivery, offering the convenience of once-weekly administration, flat pharmacokinetic profiles, and glycemic efficacy and safety comparable to those of daily basal analogues while reducing injection burden and improving patient satisfaction. With regard to bolus therapy, faster-acting aspart and ultrarapid lispro achieve accelerated absorption through novel excipient engineering, enabling more flexible mealtime dosing and improved postprandial glucose control compared to their traditional counterparts. Looking ahead, there are promising innovations on the horizon, including glucose-responsive insulins, artificial intelligence–driven automated insulin delivery, and the continued pursuit of oral insulin. Together, these advances represent an accelerating trajectory toward more physiological, convenient, and, most importantly, safe insulin therapy.