Insulin icodec

Insulin icodec
Clinical data
Pronunciation/ˌɪnsəlɪn ˈaɪkoʊdɛk/
IN-sə-lin EYE-koh-dek
Trade namesAwiqli
AHFS/Drugs.comMonograph
MedlinePlusa626058
Pregnancy
category
  • AU: B3
Routes of
administration		Subcutaneous injection
ATC code
Legal status
Legal status
Identifiers
  • (1a-21a),(1b-29b)-Insulin (human), 14a-L-glutamic acid-16b-L-histidine-25b-L-histidine-29b-(N6-(N-(19-carboxy-1-oxononadecyl)-L-gamma-glutamyl-2-(2-(2-aminoethoxy)ethoxy)acetyl-2-(2-(2-aminoethoxy)ethoxy)acetyl)-L-lysine)-
CAS Number
PubChem CID
DrugBank
UNII
ChEMBL
Chemical and physical data
FormulaC280H435N71O87S6
Molar mass6380.33 g·mol−1

Insulin icodec, sold under the brand name Awiqli, is an ultralong-acting basal insulin analogue used in the treatment of diabetes. It is administered by subcutaneous injection once weekly. It was developed by Novo.

Insulin icodec was designed to provide basal insulin coverage with once-weekly dosing.

It is approved for medical use in Canada, the European Union, Australia, and in the United States.

Medical uses

Insulin icodec is used as a basal insulin to improve glycemic control in adults with diabetes.

Indications vary by jurisdiction. In the United States, insulin icodec is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. In the European Union, insulin icodec is authorized for adults with diabetes. In people with type 1 diabetes, it is indicated together with short-acting insulin to cover mealtime insulin requirements. In people with type 2 diabetes, it may be used alone or with other diabetes medicines, including short-acting insulin.[citation needed]

Adverse effects

The most common adverse effect of insulin icodec is hypoglycemia.

Chemistry

Insulin icodec is an acylated analogue of human insulin. Like human insulin, it consists of two peptide chains linked by disulfide bonds. It was engineered with three amino acid substitutions, A14E, B16H, and B25H, and a C20 icosane fatty diacid-containing side chain attached at lysine B29 through a hydrophilic linker. This side chain imparts strong, reversible binding to albumin. The amino acid substitutions provide molecular stability and attenuate insulin receptor binding, contributing to its longer duration of action.

Society and culture

Insulin icodec was approved for medical use in Canada in March 2024.

In March 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for Awiqli, for diabetes. Insulin icodec was authorized for medical use in the European Union in May 2024.

In Australia, insulin icodec was approved in 2024.

Insulin icodec was approved for medical use in the United States in March 2026.

Names

Insulin icodec is the international nonproprietary name.

Insulin icodec is sold under the brand name Awiqli.

Research

Pharmacology

Preclinical and early clinical pharmacology studies characterized insulin icodec as a basal insulin analogue. The molecular modifications were intended to create an albumin-bound circulating depot, while preserving insulin receptor-mediated metabolic activity and limiting mitogenic activity relative to human insulin.

Clinical trials

The phase 1 clinical pharmacology trial described by Nishimura and colleagues evaluated insulin icodec in people with type 2 diabetes using a randomized, double-blind, double-dummy, active-controlled, multiple-dose, dose-escalation design. The study reported a mean half-life of 196 hours and glucose-lowering activity distributed across the weekly dosing interval, supporting further development as a once-weekly basal insulin.

In ONWARDS 1, once-weekly insulin icodec was compared with once-daily insulin glargine U100 in adults with type 2 diabetes who had not previously used insulin. Insulin icodec was non-inferior, and statistically superior for reduction in glycated hemoglobin.

The phase III ONWARDS clinical trial program evaluated once-weekly insulin icodec in adults with diabetes. ONWARDS 3 compared weekly icodec with daily insulin degludec in insulin-naïve adults with type 2 diabetes. Icodec produced a greater reduction in glycated hemoglobin after 26 weeks, with low absolute rates of clinically significant or severe hypoglycemia in both groups.

ONWARDS 6 studied insulin icodec in adults with type 1 diabetes using a basal-bolus insulin regimen. Icodec was non-inferior to once-daily insulin degludec for reduction in glycated hemoglobin, but was associated with a higher rate of clinically significant or severe hypoglycemia.

A 2025 evidence summary for family physicians concluded that, in people with type 2 diabetes, weekly insulin icodec lowers hemoglobin A1c similarly to daily long-acting insulin glargine or degludec, while noting limited data in people or situations at higher risk for hypoglycemia.

References

  1. 1 2 3 "Awiqli (insulin icodec)". Therapeutic Goods Administration. 28 July 2024. Retrieved 12 October 2024.
  2. 1 2 3 "Awiqli Product information". Health Canada. 12 March 2024. Archived from the original on 1 April 2024. Retrieved 1 April 2024.
  3. ↑ "Awiqli- insulin icodec-abae injection, solution". DailyMed. 26 March 2026. Retrieved 1 August 2026.
  4. 1 2 3 4 5 "Awiqli EPAR". European Medicines Agency (EMA). 21 March 2024. Archived from the original on 23 March 2024. Retrieved 23 March 2024.
  5. 1 2 3 "Awiqli Product information". Union Register of medicinal products. Union Register of medicinal products. 21 May 2024. Archived from the original on 22 May 2024. Retrieved 27 May 2024.
  6. ↑ "Awiqli (insulin icodec-abae) prescribing information" (PDF). U.S. Food and Drug Administration (FDA). 2026. Retrieved 1 April 2026.
  7. 1 2 "FDA approves Novo Nordisk's Awiqli, the first and only once-weekly basal insulin treatment for adults with type 2 diabetes" (Press release). Novo Nordisk. 26 March 2026. Retrieved 1 August 2026 – via PR Newswire.
  8. ↑ Nishimura E, Pridal L, Glendorf T, Hansen BF, Hubálek F, Kjeldsen T, et al. (August 2021). "Molecular and pharmacological characterization of insulin icodec: a new basal insulin analog designed for once-weekly dosing". BMJ Open Diabetes Research & Care. 9 (1) e002301. doi:10.1136/bmjdrc-2021-002301. PMC 8378355. PMID 34413118.
  9. ↑ "Regulatory Decision Summary for Awiqli". Drug and Health Products Portal. 12 March 2024. Archived from the original on 1 April 2024. Retrieved 1 April 2024.
  10. 1 2 "Drug Approval Package: Awiqli". U.S. Food and Drug Administration (FDA). 22 June 2026. Retrieved 1 August 2026.
  11. 1 2 Kjeldsen TB, Hubálek F, Hjørringgaard CU, Tagmose TM, Nishimura E, Stidsen CE, et al. (July 2021). "Molecular Engineering of Insulin Icodec, the First Acylated Insulin Analog for Once-Weekly Administration in Humans". Journal of Medicinal Chemistry. 64 (13): 8942–8950. doi:10.1021/acs.jmedchem.1c00257. PMID 33944562. S2CID 233718893.
  12. ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 85". WHO Drug Information. 35 (1). 2021. hdl:10665/340684.
  13. ↑ Rosenstock J, Bain SC, Gowda A, Jódar E, Liang B, Lingvay I, et al. (July 2023). "Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin". The New England Journal of Medicine. 389 (4): 297–308. doi:10.1056/NEJMoa2303208. PMID 37356066. S2CID 259249866.
  14. ↑ Lingvay I, Asong M, Desouza C, Guedes EP, Lahtela JT, Kakkad R (2023). "Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial". JAMA. 330 (3): 228–237. doi:10.1001/jama.2023.11313. PMC 10354685. PMID 37459141.
  15. ↑ Russell-Jones D, Babazono T, Cailleteau R, Engberg S, Irace C, Kjaersgaard MI, et al. (November 2023). "Once-weekly insulin icodec versus once-daily insulin degludec as part of a basal-bolus regimen in individuals with type 1 diabetes (ONWARDS 6): a phase 3a, randomised, open-label, treat-to-target trial". Lancet. 402 (10413). London, England: 1636–1647. doi:10.1016/S0140-6736(23)02179-7. PMID 37863084.
  16. ↑ Dugré N (1 August 2025). "#395 Long shot: Can weekly insulin replace daily doses? – CFPCLearn". CFPCLearn. Retrieved 19 September 2025.