Insulin icodec is an ultra-long-acting basal insulin analogue authorised as Awiqli in Europe for adults with diabetes. Reversible albumin binding extends its action sufficiently for once-weekly administration; it is also the insulin component of Kyinsu/IcoSema.

Established. Review the research and limitations before relying on this record.

Insulin icodec activates the human insulin receptor to promote peripheral glucose uptake and suppress hepatic glucose production. Three amino-acid substitutions reduce receptor affinity and enzymatic clearance, while a C20 fatty-diacid side chain produces greater than 99% reversible albumin binding. The albumin-bound pool is largely inactive and releases active insulin gradually across the week.

The EMA product information reports an approximately one-week subcutaneous half-life, low week-to-week variability and steady state after roughly two to four weekly administrations. Exposure is dose proportional across the therapeutic range. Degradation follows the same general pathways as human insulin and produces inactive metabolites.

Awiqli received European marketing authorisation in May 2024 for adult diabetes after the ONWARDS programme. In insulin-naive type 2 diabetes, ONWARDS 3 found once-weekly icodec non-inferior and statistically superior for HbA1c reduction versus daily degludec, with a higher rate of clinically significant or severe hypoglycaemia during the 26-week treatment period. In type 1 diabetes, ONWARDS 6 found non-inferior HbA1c but substantially more clinically significant or severe hypoglycaemia than daily degludec.

Hypoglycaemia is the principal and potentially life-threatening risk. The EMA label also describes injection-site reactions, hypersensitivity, lipodystrophy, weight gain, oedema, and the need for particular care during switching because a dosing error persists for about a week. The higher hypoglycaemia rate in ONWARDS 6 is why European product information advises that once-weekly icodec is not the preferred basal insulin for type 1 diabetes.

This is a source-backed summary, not a recommendation. Read the mechanism, pharmacokinetic, human-evidence and reported-effect fields separately: a mechanism is not an outcome. Availability, legal status and product quality differ by jurisdiction; consult a qualified clinician.