Once-weekly basal insulin therapy in type 1 diabetes: A paradigm shift or a work in progress?

Abstract Purpose Type 1 diabetes mellitus (T1DM) requires lifelong basal and bolus insulin therapy to maintain glycemic control, often necessitating multiple daily injections. Recently, the development of once-weekly basal insulin formulations, insulin icodec and insulin efsitora alfa, has introduced the possibility of reducing injection burden while preserving efficacy. This review evaluates the pharmacological properties, clinical trial data, patient considerations, and regulatory landscape of these novel therapies to determine their potential role in T1DM management. Summary Insulin icodec and insulin efsitora alfa utilize distinct structural modifications to extend their duration of action, allowing for weekly dosing. Insulin icodec achieves prolonged activity through enhanced albumin binding and reduced insulin receptor affinity, while insulin efsitora alfa utilizes Fc-fusion technology and neonatal Fc receptor recycling. Phase 3 trials (the ONWARDS-6 trial for insulin icodec and the QWINT-5 trial for insulin efsitora), demonstrated that both insulins achieved glycemic control comparable to that provided by once-daily basal insulin degludec. However, both formulations were associated with a higher incidence of hypoglycemia, particularly during the titration period. Additionally, patient-reported outcomes varied, with insulin efsitora being associated with greater treatment satisfaction than insulin icodec. Conclusion Once-weekly basal insulin represents a potential paradigm shift in T1DM management, offering convenience but presenting challenges related to hypoglycemia risk, patient acceptance, and regulatory hurdles. Further research is needed to refine titration protocols, identify optimal patient populations, and address safety concerns before these therapies can become standard of care.