Basal weekly insulins: the way of the future!

Basal insulin treatment is indispensable for patients with type 1 diabetes and often required by many with type 2 diabetes. Incremental advances lengthening the duration of action of insulin analogs and reducing pharmacodynamic variability have resulted in truly once-daily, long-acting basal insulin analogs. In the quest for better basal insulins to facilitate improvements in glycemic control and long-term outcomes, the driving need is to remove barriers delaying timely initiation of basal insulin, to maximize treatment adherence and persistence and reduce treatment burden without increasing risk of hypoglycemia. We review the range of investigational once-weekly insulins and their molecular strategies and profiles. Currently, the two most advanced clinical development programs are: (1) basal insulin icodec, an insulin analog acylated with a C20 fatty diacid (icosanedioic acid) side chain (Novo Nordisk) and (2) basal insulin Fc, a fusion protein that combines a single-chain insulin variant with a human immunoglobulin G fragment crystallizable domain (Eli Lilly). Available phase 2 data for these two once-weekly agents show comparable glycemic control to existing once-daily insulin analogs, with no greater risk of hypoglycemia. While phase 3 data are awaited to confirm efficacy and safety, we provide future clinical perspectives on practical considerations for the potential use of once-weekly insulins.