Pharmacokinetics, Clinical Efficacy, and Safety of Once-Weekly Insulin Icodec: A Structured Narrative Review...

Suboptimal adherence to daily basal insulin remains a significant barrier to achieving glycemic targets in patients with diabetes mellitus. Insulin icodec is a novel, once-weekly basal insulin analog designed to reduce injection burden and improve treatment compliance. This review evaluates the pharmacological profile, clinical efficacy, and safety of insulin icodec by synthesizing data from the comprehensive Phase 3 ONWARDS clinical trial program. A structured narrative review of recent literature (2022-2026) was conducted, focusing on randomized controlled trials (RCTs), pharmacokinetic studies, and meta-analyses comparing insulin icodec with daily basal insulins (glargine U-100 and degludec). Insulin icodec achieves a half-life of approximately 196 hours through reversible binding to albumin, enabling a once-weekly dosing interval. In patients with type 2 diabetes (T2D), the ONWARDS 1-5 trials demonstrated that icodec provides non-inferior, and in several cohorts, superior, reductions in glycated hemoglobin (HbA1c) compared to daily basal insulins, with a comparable risk of clinically significant or severe hypoglycemia. Time-in-range (TIR) metrics were significantly improved. However, in patients with type 1 diabetes (T1D) (ONWARDS 6), while glycemic efficacy was non-inferior, icodec was associated with a statistically significant increase in the risk of severe or clinically significant hypoglycemia compared to insulin degludec. Insulin icodec may represent an important advancement in the management of T2D, offering improved glycemic control with a substantially reduced injection burden. While its use in T1D requires cautious consideration due to hypoglycemia risks, icodec has the potential to become a preferred standard of care for insulin-requiring T2D globally.