Insulin icodec
The first weekly basal insulin, which beat daily insulins on blood sugar in type 2 diabetes and raised hypoglycaemia in type 1
Insulin icodec binds albumin in the blood and releases slowly enough for once-weekly injection. In type 2 diabetes it beat daily insulin on HbA1c; in type 1 it doubled serious low blood sugar, and the US label covers type 2 only.
What is it?
Basal insulin covers the body's background need between meals, and every approved one until 2026 was injected daily. Icodec was engineered to bind albumin, the main protein in blood, forming a circulating depot that releases insulin slowly enough for weekly dosing; its half-life is about a week. FDA approved it as Awiqli in March 2026 for adults with type 2 diabetes.
The type 2 trials favoured it. In ONWARDS 1, 984 people new to insulin took icodec or daily glargine for 52 weeks: HbA1c fell 1.55 points against 1.35, and time in range was 71.9% against 66.9%. ONWARDS 2 and 3, against degludec, also found it superior on HbA1c. A network meta-analysis put it ahead of efsitora, the other weekly insulin in development, on HbA1c, with more mild lows. Results held across kidney-function groups.
Hypoglycaemia is the counterweight. In ONWARDS 1, clinically significant or severe episodes ran at 0.30 a person-year against 0.16 on glargine, a difference that did not reach significance. In type 1 diabetes it did: ONWARDS 6 found HbA1c non-inferior but hypoglycaemia nearly doubled, 19.9 against 10.4 events a patient-year. Pooled across all six trials, serious adverse events and hypersensitivity were similar to daily insulin, with somewhat more injection-site reactions.
Practical questions are being answered. A 2026 trial found people could switch from daily basal insulin without the extra first dose and still match glargine; hospital stays during the trials went no differently from those on daily insulin. Pairing it with weekly semaglutide in one injection lowered HbA1c far more than icodec alone. Adding weekly semaglutide later, in a separate single-arm study, lowered HbA1c by a further 1.2 points and weight by nearly 4 kg while the icodec dose fell. In ONWARDS 5, people followed a dosing app's weekly advice for 95% of doses.
FDA's first answer, in July 2024, was a complete response letter citing manufacturing and the type 1 indication, and the label that followed covers type 2 only. A weekly dose is also slower to correct, so the label asks for close monitoring when patients switch.
Mechanism of Action
Insulin icodec binds albumin to form a slow-release depot in the blood, so one injection covers a week of basal insulin.
Albumin binding
Engineered to bind albumin, so most icodec circulates bound and is released gradually.
Weekly half-life
Half-life about one week after subcutaneous injection (Awiqli label 12.3).
Insulin receptor
Once released from albumin it acts at the insulin receptor to lower glucose.
Published Research
These are the trials that describe insulin icodec, read from their PubMed abstracts: three phase 3 trials in type 2 diabetes and one in type 1.
ONWARDS 1: against glargine
984 adults new to insulin took weekly icodec or daily glargine U100. At 52 weeks HbA1c fell 1.55 points against 1.35 (superior) and time in range was 71.9% against 66.9%; serious hypoglycaemia ran at 0.30 against 0.16 events per person-year.
ONWARDS 3: double-masked
588 insulin-naive adults took weekly icodec or daily degludec, double-masked with matching placebos. HbA1c fell from 8.6% to 7.0% against 8.5% to 7.2%, non-inferior and superior, with no difference in fasting glucose, dose or weight.
ONWARDS 2: switching
526 adults already on daily basal insulin switched to weekly icodec or daily degludec. At 26 weeks HbA1c was 7.20% against 7.42%, a difference of 0.22 points, demonstrating superiority.
ONWARDS 6: type 1 diabetes
582 adults with type 1 diabetes took weekly icodec or daily degludec with mealtime insulin. HbA1c was non-inferior, but serious hypoglycaemia was significantly higher on icodec: 19.9 against 10.4 events per patient-year.
Switching without a loading dose
In 412 people on basal insulin switched without the usual one-time extra first dose, icodec was non-inferior to glargine for HbA1c at 26 weeks (7.2% against 7.5%) and improved time in range, with no rise in self-measured glucose after the switch.
COMBINE 1: adding weekly semaglutide
In 1,291 adults, the weekly icodec-semaglutide combination lowered HbA1c 1.55 points against 0.89 on icodec alone over 52 weeks.
Hospital stays during treatment
Across ONWARDS 1-6, hospitalisation rates and lengths of stay were similar on icodec and daily insulin, and icodec doses stayed fairly stable around admissions.
By kidney function
In 3,763 ONWARDS 1-5 participants, glucose lowering and weight change with icodec were broadly consistent across kidney-function subgroups, with no consistent trend in insulin dose.
Adding semaglutide later
In 94 people on icodec who added weekly semaglutide, HbA1c fell from 7.88% to 6.66% over 52 weeks and weight by 3.85 kg, while the weekly icodec dose fell by about a quarter. There was no control arm.
Dosing by app in ONWARDS 5
Insulin-naive participants changed only 5% of doses away from the app's weekly guidance; clinicians overrode it at least once for 56.7%, mostly to raise the dose, and better adherence went with lower fasting glucose.
Pooled safety, ONWARDS 1-6
Across 2,170 people on icodec and 2,170 on daily comparators, rates of all, serious and severe adverse events and hypersensitivity were similar; injection-site reactions were somewhat more common on icodec (5.86 against 3.66 per 100 patient-years).
Against efsitora
A network meta-analysis of 13 trials (7,402 participants) found icodec lowered HbA1c more than the other weekly insulin, efsitora, with more level 1 hypoglycaemia and no difference in serious lows.
Dosing Data
Awiqli is injected under the skin once a week, with the dose individualised to fasting glucose.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the Awiqli label and the trials above.
Contraindications & Cautions
Set by the label.
Legal Status
Insulin icodec is approved in the US as Awiqli.
Frequently Asked Questions
?What is insulin icodec?
A basal insulin that binds albumin in the blood and releases slowly, so it is injected once a week rather than daily.
?Who is it approved for?
Adults with type 2 diabetes, as Awiqli. It is not approved for type 1 diabetes.
?Why not type 1?
In the type 1 trial, serious hypoglycaemia was nearly twice as common as on daily degludec, 19.9 against 10.4 events a patient-year.
?Does it work better than daily insulin?
In type 2 diabetes, three phase 3 trials found it lowered HbA1c slightly more than daily glargine or degludec.
References
- [fda-pi] Awiqli (insulin icodec-abae) Prescribing Information, sections 1 and 2 (DailyMed, March 26, 2026).
- [pubmed] Rosenstock J, et al. "Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin." N Engl J Med, 2023;389(4):297-308. PMID: 37356066.
- [pubmed] Lingvay I, et al. "Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial." JAMA, 2023;330(3):228-237. PMID: 37354562.
- [pubmed] Philis-Tsimikas A, et al. "Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial." Lancet Diabetes Endocrinol, 2023;11(6):414-425. PMID: 37148899.
- [pubmed] Russell-Jones D, 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. PMID: 37863084.
- [other] Novo Nordisk A/S, Form 6-K, July 10, 2024: FDA complete response letter for insulin icodec.
- [other] US FDA, Drugs@FDA (openFDA): AWIQLI FLEXTOUCH, BLA 761326, original approval March 26, 2026. Read September 30, 2026.
- [other] EMA medicines dataset: Awiqli (insulin icodec), authorised May 17, 2024. Read October 5, 2026.
- [pubmed] Bajaj HS, et al. "Once-Weekly Insulin Icodec: Safety Profile in Type 2 and Type 1 Diabetes Based on a Pooled Analysis of ONWARDS 1-6." Endocr Pract, 2026;32(10):1475-1482. PMID: 42119975.
- [clinical-trial] Rosenstock J, et al. "Simplified Switching to Once-Weekly Insulin Icodec Without an Initial One-Time Additional Dose Versus Once-Daily Insulin Glargine U100 in Basal Insulin-Treated Type 2 Diabetes (ONWARDS 10): A Randomised Controlled Trial." Diabetes Obes Metab, 2026;28(9):7791-7801. PMID: 42168822.
- [clinical-trial] Mathieu C, et al. "Once‑weekly IcoSema versus once‑weekly insulin icodec in type 2 diabetes management (COMBINE 1): an open‑label, multicentre, treat‑to‑target, randomised, phase 3a trial." Lancet Diabetes Endocrinol, 2025;13(7):568-579. PMID: 40482671.
- [pubmed] Li J, et al. "Efficacy and safety of insulin icodec compared with insulin efsitora in patients with type 2 diabetes: a systematic review and network meta-analysis." Front Endocrinol (Lausanne), 2026;17:1902260. PMID: 42666211.
- [pubmed] Philis-Tsimikas A, et al. "Insights on Hospitalisations from the Phase 3a ONWARDS 1-6 Trials of Once-Weekly Insulin Icodec." Diabetes Ther, 2025;16(8):1615-1631. PMID: 40465144.
- [pubmed] Rossing P, et al. "Efficacy and hypoglycaemia outcomes with once-weekly insulin icodec versus once-daily basal insulin in individuals with type 2 diabetes by kidney function: A post hoc participant-level analysis of the ONWARDS 1-5 trials." Diabetes Obes Metab, 2025;27(4):2259-2270. PMID: 39930546.
- [pubmed] Strojek K, et al. "Efficacy and Safety of Intensifying Once-Weekly Insulin Icodec Treatment With Once-Weekly Semaglutide in Adults With Type 2 Diabetes: A Single-Arm, Open-Label, Treat-to-Target, Phase 3b Trial (ONWARDS 8)." Diabetes Obes Metab, 2026;28(9):8515-8522. PMID: 42387310.
- [pubmed] Bajaj HS, et al. "Adherence to app-based dose guidance for once-weekly insulin icodec in insulin-naive individuals with type 2 diabetes: Post hoc analysis of ONWARDS 5." Diabetes Obes Metab, 2025;27(10):5514-5523. PMID: 40803997.
Sources & Citations
Studies were read from their PubMed abstracts; the Awiqli label (DailyMed, March 26, 2026) was read September 30, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.