Once-Weekly Insulin Icodec: A Review of its Pharmacokinetic and Pharmacodynamic Properties

Insulin icodec is a novel long-acting basal insulin engineered for once-weekly administration. Structural modifications enhance reversible albumin binding and slow insulin receptor binding, resulting in protracted exposure and glucose-lowering effect. The clinical pharmacology of icodec was characterised using consistent methodology across populations with type 2 or type 1 diabetes. Icodec has a half-life of approximately 7 days and pharmacokinetic and pharmacodynamic profiles covering the full weekly dosing interval. It displays dose-proportional exposure, week-to-week predictability, with an intra-individual coefficient of variation in total exposure of 5.9%, and a comparable glucose-lowering effect independent of injection region. Following treatment initiation, icodec clinical steady state is achieved after 3-4 weeks-this can be reduced by 1 week if the first icodec dose is 50% increased. If, unintentionally, a too high insulin dose is administered, hypoglycaemia risk with icodec is comparable to that of daily basal insulin, including robust physiological counter-regulation to hypoglycaemia. During exercise or prolonged fasting, glucose metrics remained within recommended targets, with no clinically significant or severe hypoglycaemia, and supplemental glucose, when required, effectively prevented clinically relevant hypoglycaemia. The pharmacological properties of icodec are preserved across patient characteristics, without a clinically relevant impact of age, sex, diabetes type, race, ethnicity, renal or hepatic impairment, serum albumin or anti-insulin icodec antibody level. These findings support predictable, sustained basal insulin coverage suitable for once-weekly administration. This review summarises the evidence on icodec pharmacokinetic and pharmacodynamic properties and discusses how these characteristics translate into clinical benefits and specific clinical considerations compared with existing once-daily basal insulin.