Insulin icodec, sold under the brand name Awiqli, is an ultralong-acting basal insulin analogue used in the treatment of diabetes mellitus.[1] It is administered by subcutaneous injection once weekly.[2] It was developed by Novo Nordisk.
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| Trade names | Awiqli |
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| Routes of administration | Subcutaneous injection |
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| Formula | C280H435N71O87S6 |
| Molar mass | 6380.33 g·mol−1 |
Insulin icodec was designed to provide basal insulin coverage with once-weekly dosing.[3] Its long duration of action results from molecular modifications that increase reversible albumin binding and reduce insulin receptor binding and clearance. In a clinical pharmacology trial in people with type 2 diabetes, insulin icodec had a mean half-life of 196 hours and a glucose-lowering effect distributed across the one-week dosing interval.
Insulin icodec was approved for medical use in Canada in March 2024,[4] in the European Union in May 2024,[5] in Australia in June 2024,[6] and in the United States in March 2026.[7]
Medical uses
editInsulin icodec is used as a basal insulin to improve glycemic control in adults with diabetes mellitus. It is injected under the skin once weekly, on the same day each week.
In the United States, insulin icodec-abae is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. In the European Union, Awiqli is authorized for adults with diabetes mellitus.[8] Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In people with type 1 diabetes, it is used 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.
Insulin icodec is not used to treat diabetic ketoacidosis.
Adverse effects
editThe most common adverse effect of insulin icodec is hypoglycemia. As with other insulin products, severe hypoglycemia can be life-threatening. Because insulin icodec has a long duration of action, recovery from hypoglycemia may be delayed compared with shorter-acting insulins.
Other adverse effects associated with insulin icodec and insulin therapy include hypersensitivity reactions, injection-site reactions, lipodystrophy, localized cutaneous amyloidosis, hypokalemia, edema, and weight gain.
Medication errors are a safety concern because insulin icodec is administered once weekly. Product labeling recommends checking the product label before administration, using the medicine only once weekly, and avoiding transfer of the medicine from the prefilled pen into a syringe. The European Medicines Agency has recommended educational materials for patients and healthcare professionals to reduce the risk of medication errors.
Pharmacology
editPharmacokinetics
editAlbumin binding produces a circulating depot that contributes to prolonged insulin action and slower clearance. In clinical pharmacology studies, insulin icodec had a mean half-life of 196 hours. This is substantially longer than the approximately 25-hour half-life reported for insulin degludec, an earlier ultralong-acting basal insulin analogue. The pharmacokinetic and pharmacodynamic profile supports once-weekly dosing. In a randomized, double-blind, double-dummy, active-controlled, multiple-dose, dose-escalation clinical pharmacology trial in people with type 2 diabetes, insulin icodec was reported to be well tolerated and to have pharmacokinetic and pharmacodynamic properties suitable for once-weekly use. The trial reported close to even distribution of glucose-lowering effect across the one-week dosing interval. The trial was registered as NCT02964104.
Pharmacodynamics
editThe extended duration of insulin icodec results from a combination of strong reversible albumin binding, reduced insulin receptor affinity, and reduced clearance. These properties create a long-acting circulating depot from which active insulin icodec is gradually available to insulin receptors. In vitro studies reported that insulin icodec activates insulin receptor-mediated signaling and metabolic responses in a dose-dependent manner, similar to human insulin. Its affinity for the insulin-like growth factor 1 receptor was proportionately lower than its binding to the insulin receptor, and its mitogenic effect in tested human cell systems was low relative to human insulin.
Chemistry
editInsulin 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.[9] The C20 fatty diacid-containing side chain imparts strong, reversible binding to albumin. The amino acid substitutions provide molecular stability and attenuate insulin receptor binding, contributing to the prolonged duration of action.[9]
Society and culture
editLegal status
editInsulin icodec was approved for medical use in Canada in March 2024. Health Canada authorized Awiqli for once-weekly treatment of adults with diabetes mellitus to improve glycemic control.
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, intended for the treatment of diabetes. The applicant was Novo Nordisk A/S. Insulin icodec was authorized for medical use in the European Union in May 2024.
In Australia, Awiqli was approved by the Therapeutic Goods Administration in 2024 for the treatment of type 1 and type 2 diabetes in adults.
In the United States, the U.S. Food and Drug Administration approved insulin icodec-abae in March 2026 for adults with type 2 diabetes.
Names
editInsulin icodec is the international nonproprietary name.[10] In the United States, the proper name is insulin icodec-abae. It is sold under the brand name Awiqli.
Research
editEarly pharmacology
editPreclinical and early clinical pharmacology studies characterized insulin icodec as a basal insulin analogue designed for once-weekly administration. 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.
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.
Phase 3 trials
editThe phase 3 ONWARDS clinical trial program evaluated once-weekly insulin icodec in adults with diabetes mellitus.
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, to insulin glargine U100 for reduction in glycated hemoglobin.[11]
ONWARDS 3 compared once-weekly insulin icodec with once-daily insulin degludec in insulin-naïve adults with type 2 diabetes. Insulin icodec produced a greater reduction in glycated hemoglobin after 26 weeks, with low absolute rates of clinically significant or severe hypoglycemia in both groups.[12]
ONWARDS 6 studied insulin icodec in adults with type 1 diabetes using a basal-bolus insulin regimen. Insulin 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.[13]
A 2025 evidence summary for family physicians concluded that, in people with type 2 diabetes, once-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.[14]
References
edit- ↑ "Awiqli Product information". Health Canada. 12 March 2024. Archived from the original on 1 April 2024. Retrieved 1 April 2024.
- ↑ "Awiqli (insulin icodec-abae) prescribing information" (PDF). U.S. Food and Drug Administration. 2026. Retrieved 1 April 2026.
- ↑ 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.
- ↑ "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.
- ↑ "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.
- ↑ "Awiqli (insulin icodec)". Therapeutic Goods Administration. 28 July 2024. Retrieved 12 October 2024.
- ↑ "FDA Approves Awiqli (insulin icodec-abae) as the First and Only Once-Weekly Basal Insulin Treatment for Adults with Type 2 Diabetes". Drugs.com (Press release). 26 March 2026. Retrieved 1 April 2026."Awiqli (insulin icodec-abae) FDA Approval History". Drugs.com. 30 March 2026. Retrieved 1 April 2026.
- ↑ "Awiqli EPAR". European Medicines Agency (EMA). European Medicines Agency. 21 March 2024. Archived from the original on 23 March 2024. Retrieved 23 March 2024.
- 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.
- ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 85". WHO Drug Information. 35 (1). 2021. hdl:10665/340684.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Dugré N (1 August 2025). "#395 Long shot: Can weekly insulin replace daily doses? – CFPCLearn". CFPCLearn. Retrieved 19 September 2025.
External links
edit- Clinical trial number NCT02964104 for "A Trial Investigating the Pharmacokinetic and Pharmacodynamic Properties of Insulin 287 Once Weekly in Subjects With Type 2 Diabetes" at ClinicalTrials.gov
- Clinical trial number NCT04460885 for "A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Glargine, in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 1)" at ClinicalTrials.gov
- Clinical trial number NCT04795531 for "A Research Study to Compare Two Types of Insulin, a New Insulin, Insulin Icodec and an Available Insulin, Insulin Degludec, in People With Type 2 Diabetes Who Have Not Used Insulin Before (ONWARDS 3) (ONWARDS 3)" at ClinicalTrials.gov
- Clinical trial number NCT04770532 for "A Research Study to Compare Two Types of Insulin, a New Weekly Insulin, Insulin Icodec and an Available Daily Insulin, Insulin Degludec, in People With Type 2 Diabetes Who Use Daily Insulin (ONWARDS 2)" at ClinicalTrials.gov
- Clinical trial number NCT04880850 for "A Research Study to Compare Two Types of Insulin, a New Weekly Insulin, Insulin Icodec and an Available Daily Insulin, Insulin Glargine, Both in Combination With Mealtime Insulin, in People With Type 2 Diabetes Who Use Daily Insulin and Mealtime Insulin (ONWARDS 4)" at ClinicalTrials.gov