Once-weekly insulin icodec (Awiqli)

Insulin icodec (brand name Awiqli) is the first basal insulin you inject once a week instead of once a day. It is a background ("basal") insulin: it does not cover meals, so in type 1 diabetes it must always be paired with a separate rapid mealtime insulin.¹ It is not a mealtime, ultra-rapid, or inhaled insulin.

How it is engineered. Three amino-acid changes (A14E, B16H, B25H) plus a 20-carbon fatty-diacid side chain make icodec bind tightly but reversibly to albumin, the most abundant protein in blood.² Most of an injected dose sits in this circulating, essentially inactive albumin "reservoir" and is released slowly, while a deliberately weakened grip on the insulin receptor slows how fast it is cleared.² A separate clearance route — splitting of the insulin into its two chains — was also stabilized, further lengthening its life in the body.³

PK/PD with real numbers. The half-life is about 196 hours (~8 days), with median time to peak concentration around 16 hours; because of the long half-life, the depot builds up over the first 3–4 weekly injections before reaching steady state.² Critically for a weekly basal, the glucose-lowering effect is spread almost evenly across the seven days: each day carries only 12.0% to 16.3% of the weekly effect, against 14.3% for a perfectly flat profile.² In practice that means a near-peakless action — the opposite of a mealtime insulin, and exactly what you want from a basal.

Absorption variability and a loading dose. The albumin buffer is designed to smooth out day-to-day swings, and when switching from a daily basal an extra one-time loading dose (about double the weekly amount) is used to reach steady state faster.² But "flat in theory" is not the same as "safe in type 1": in the ONWARDS 6 trial (582 adults with type 1 diabetes), icodec matched daily degludec on HbA1c at 26 weeks (−0.47 vs −0.51 percentage points) but caused nearly twice the clinically significant or severe hypoglycemia — 19.9 vs 10.4 events per patient-year (rate ratio 1.9).¹

Behaviour around exercise and delivery. Because a whole week of basal is always on board, it cannot be dialled back ahead of activity — a real limitation for the glucose swings of type 1 life.⁴ It is given as a subcutaneous injection from a prefilled pen, and is a concentrated U700 (700 units/mL) formulation so the weekly volume stays small.⁵

Approvals. Icodec was first approved in Switzerland and Canada (March 2024) and across the EU on 17 May 2024 for diabetes in adults; the EU label explicitly warns that in type 1 diabetes hypoglycaemia is more common than with daily basal and that it should be started "only if there are clear benefits."⁶ It is also approved in the UK, Japan, Australia and other markets, and in China (type 2).⁴ In the US the FDA issued a Complete Response Letter in July 2024, citing manufacturing and the type 1 indication;⁷ after a type-2-only resubmission,⁸ the FDA approved Awiqli for type 2 diabetes only on 26 March 2026 — it remains not US-approved for type 1 diabetes.⁵

Access and cost. It is a branded analog with no biosimilars; pricing and formulary status vary by country, and type 1 use is off-label or unsupported in most places.

What's coming. Novo Nordisk is advancing IcoSema, a once-weekly fixed combination of icodec and the GLP-1 drug semaglutide, but that program targets type 2 diabetes and is not being filed in the US.⁴ For type 1 specifically, the open question is whether smarter titration or pairing with automated delivery can tame the hypoglycemia signal — until then, weekly basal in type 1 stays a convenience-versus-safety trade-off rather than a clear win.⁴

References

1. Russell-Jones D, Babazono T, Cailleteau R, et al. 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 (2023);402(10413):1636–1647. https://doi.org/10.1016/S0140-6736%2823%2902179-7 ↩ ↩²

2. Nishimura E, Pridal L, Glendorf T, et al. Molecular and pharmacological characterization of insulin icodec: a new basal insulin analog designed for once-weekly dosing. BMJ Open Diabetes Research & Care (2021);9(1):e002301. https://doi.org/10.1136/bmjdrc-2021-002301 ↩ ↩² ↩³ ↩⁴ ↩⁵

3. Hubálek F, Cramer CN, Helleberg H, et al. Enhanced disulphide bond stability contributes to the once-weekly profile of insulin icodec. Nature Communications (2024);15:6124. https://doi.org/10.1038/s41467-024-50477-9 ↩

4. Denimal D. Emerging perspectives on once-weekly insulins in type 1 and type 2 diabetes: a mini-review. Frontiers in Endocrinology (2025);16:1656884. https://doi.org/10.3389/fendo.2025.1656884 ↩ ↩² ↩³ ↩⁴

5. Novo Nordisk. Awiqli approved in the US, the first and only once-weekly basal insulin treatment for adults with type 2 diabetes (insulin icodec-abae injection, 700 units/mL). GlobeNewswire (26 March 2026). https://www.globenewswire.com/news-release/2026/03/26/3263519/0/en/novo-nordisk-a-s-awiqli-approved-in-the-us-the-first-and-only-once-weekly-basal-insulin-treatment-for-adults-with-type-2-diabetes.html ↩ ↩²

6. European Medicines Agency. Awiqli (insulin icodec) — EPAR / medicine overview. EMA (marketing authorisation 17 May 2024). https://www.ema.europa.eu/en/medicines/human/EPAR/awiqli ↩

7. Novo Nordisk. Novo Nordisk receives Complete Response Letter in the US for once-weekly basal insulin icodec. GlobeNewswire (10 July 2024). https://www.globenewswire.com/news-release/2024/07/10/2911476/0/en/Novo-Nordisk-receives-Complete-Response-Letter-in-the-US-for-once-weekly-basal-insulin-icodec.html ↩

8. Novo Nordisk. Novo Nordisk resubmits Awiqli to the FDA with potential to be the first once-weekly basal insulin treatment for adults with type 2 diabetes. PR Newswire (29 September 2025). https://www.prnewswire.com/news-releases/novo-nordisk-resubmits-awiqli-to-the-fda-with-potential-to-be-the-first-once-weekly-basal-insulin-treatment-for-adults-with-type-2-diabetes-302568645.html ↩