Insulin icodec

Awiqli, insulin icodec-abae, NN1436

Metabolic & weight

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Note on this profile. Insulin icodec is an approved prescription medicine, not a research-only compound. This page explains the published science. Insulin of any kind can cause life-threatening low blood sugar and is not a compound anyone uses outside clinical care; there is no community-use context for it.

1What it is

Insulin icodec is a once-weekly basal insulin. Human insulin is a 51-amino-acid two-chain peptide hormone; icodec is that molecule with three substitutions that slow receptor binding and degradation, plus a long fatty diacid chain attached at position B29 that lets it ride on albumin in the blood. The albumin reservoir releases it slowly, so a single injection covers background insulin needs for a week.

It was the first weekly insulin to reach market. Health Canada approved it in March 2024, the European Commission authorised it in May 2024 following a positive CHMP opinion, the TGA approved it in Australia in 2024, and the FDA approved it in March 2026 as insulin icodec-abae for adults with type 2 diabetes. The EU and Australian labels cover type 1 as well as type 2 diabetes; the US label is type 2 only. Cross-link: insulin (#128) for the parent molecule and the analogue class generally.

2How it's thought to work

Albumin binding as a depot. The fatty diacid side chain binds albumin reversibly. At steady state the great majority of injected drug is albumin-bound and inactive; a small free fraction is released continuously.

Reduced receptor affinity and clearance. The amino-acid substitutions lower affinity for the insulin receptor and slow receptor-mediated clearance, which further flattens the exposure curve.

The result is a near-flat profile. Within-week variation in insulin action is modest, which is what makes weekly dosing clinically workable rather than a once-weekly spike.

Downstream it is ordinary insulin action. glucose uptake into muscle and fat, suppression of hepatic glucose output, suppression of lipolysis.

Insulin engineered to bind albumin and release slowly, giving a once-weekly basal insulin. The same receptor and the same flat profile, held for seven days instead of one.Schematic — not to scale

A practical consequence of the long half-life: it takes roughly three to four weeks to reach steady state, and any dosing error persists for days rather than hours.

3What the research shows

Glycaemic control in insulin-naïve type 2 diabetes

ONWARDS 1 (n≈984, 78 weeks) compared weekly icodec with daily insulin glargine U100 in insulin-naïve type 2 diabetes and found icodec non-inferior and statistically superior for HbA1c reduction, with more time in range (Rosenstock 2023, NEJM). ONWARDS 3 (n≈588, 26 weeks) compared icodec with daily degludec in the same population and reported a greater HbA1c reduction with low rates of clinically significant or severe hypoglycaemia in both arms (Mathieu 2023, JAMA). [1][2][4]

Switching from daily basal insulin in type 2 diabetes

ONWARDS 2 (switching from degludec or glargine) and ONWARDS 4 (basal-bolus regimens) reported non-inferior HbA1c with similar hypoglycaemia rates (Philis-Tsimikas 2023, Lancet Diabetes Endocrinol; Mathieu 2023, Lancet). ONWARDS 5 was a real-world-style trial in primary care using a dose-guide app and also met its endpoint (Bajaj 2023, Ann Intern Med). [2][4][5]

Graded A, with a safety signal

Type 1 diabetes

ONWARDS 6 (n≈582) compared icodec with degludec in a basal-bolus regimen for type 1 diabetes. HbA1c was non-inferior, but the rate of clinically significant or severe hypoglycaemia was higher with icodec (Russell-Jones 2023, Lancet Diabetes Endocrinol). This is the main reason regulators have treated type 1 use more cautiously than type 2. [6]

Hypoglycaemia overall

Across the type 2 trials, rates of severe or clinically significant hypoglycaemia were broadly comparable to daily basal insulins. The pattern of hypoglycaemia differs: with weekly dosing, events cluster in the days after injection in some analyses, and a reduced dose cannot be "un-given".

4Reported side effects and interactions

Literature-reported

Hypoglycaemia is the dominant adverse effect, as with every insulin. Also reported: injection-site reactions, weight gain, peripheral oedema, and hypersensitivity reactions. In type 1 diabetes, more hypoglycaemia than daily degludec.

Community-reported

Community use. essentially none documented. Insulin is not a self-directed research compound; the community-facing risk discussed in peptide spaces concerns insulin generally rather than this analogue.

Theoretical. the long duration means that illness, reduced food intake, exercise, or an accidental double dose cannot be corrected by skipping the next dose for several days. Labels and regulators have specifically warned about weekly-versus-daily medication errors, and about transferring drug from the pen to a syringe.

Interactions. anything that lowers or raises glucose changes insulin requirement — sulfonylureas, GLP-1 receptor , SGLT2 inhibitors, corticosteroids, thiazides, beta-blockers (which can also mask hypoglycaemia symptoms), alcohol. Thiazolidinediones with insulin increase heart-failure risk.

Markers researchers commonly monitor

These follow the label and the ONWARDS protocols:

Marker	Why it's watched
HbA1c	the primary measure of effect; checked roughly every three months.
Fasting plasma glucose	the titration target in all the ONWARDS trials; weekly dose changes were driven by it.
Continuous glucose monitoring: time in range, time below range	the most informative measure for a flat weekly insulin, and the practical way to detect hypoglycaemia clustering after a dose.
Documented hypoglycaemia episodes with timing relative to injection day	the specific question weekly dosing raises.
Body weight	basal insulin typically causes modest weight gain.
Potassium	insulin drives potassium into cells; relevant in anyone with kidney disease or on potassium-affecting drugs.
eGFR and liver enzymes	insulin requirement falls as kidney or liver function declines.

Free for everyone. Safety information is never behind a paywall.

5Formulation and administration context

Supplied as a prefilled pen at a high unit concentration so that a week's dose fits a small volume. It is an aqueous solution, not a powder, and requires no preparation. There is no self-preparation route for this product and nothing here translates to vial-and-syringe practice. Injected subcutaneously once weekly on the same day each week, with sites rotated. Any change of basal insulin product is a clinical decision made with glucose monitoring in place.

6Commonly studied alongside

Short-acting mealtime insulins (in basal-bolus regimens), metformin, SGLT2 inhibitors, and GLP-1 receptor agonists including semaglutide (#3); a fixed-ratio combination with semaglutide has been studied. Cross-link: insulin (#128), insulin efsitora alfa (#242) as the other approved weekly basal insulin.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved March 2026 as Awiqli (insulin icodec-abae) for adults with type 2 diabetes; not indicated for type 1 diabetes
European Union	EMA-authorised (Awiqli) since May 2024, type 1 and type 2 diabetes in adults
United Kingdom	MHRA-licensed; prescription-only †
Australia	TGA-approved 2024 for adults with type 1 or type 2 diabetes
South Africa	Not confirmed as SAHPRA-registered †
Sport	Insulins are prohibited at all times by WADA (S4.5, hormone and metabolic modulators)

8Open questions

Whether the type 1 hypoglycaemia signal can be managed away with different titration rules or CGM-guided dosing.
How weekly dosing performs over years of real-world use, especially around intercurrent illness and hospital admission.
Whether the adherence advantage of weekly dosing translates into better long-term outcomes rather than just better convenience.

9References

1Rosenstock J et al. (2023). Weekly icodec versus daily glargine U100 in type 2 diabetes without previous insulin (ONWARDS 1). NEJM. PubMed · DOI
2Mathieu C et al. (2023). Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2). Lancet Diabetes Endocrinol. PubMed
3Lingvay I et al. (2023). Once-weekly insulin icodec vs once-daily insulin degludec in adults with insulin-naive type 2 diabetes (ONWARDS 3). JAMA. PubMed · DOI
4Mathieu C et al. (2023). Once-weekly insulin icodec versus once-daily insulin glargine U100 in adults with type 2 diabetes on a basal-bolus regimen (ONWARDS 4). Lancet. PubMed
5Bajaj HS et al. (2023). Once-weekly insulin icodec with dosing guide app versus once-daily basal insulin analogues in insulin-naive type 2 diabetes (ONWARDS 5). Ann Intern Med. PubMed · DOI
6Russell-Jones D et al. (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). Lancet Diabetes Endocrinol. PubMed · DOI
7Nishimura E et al. (2021). Molecular and pharmacological characterization of insulin icodec: a new basal insulin analog designed for once-weekly dosing. BMJ Open Diabetes Res Care. PubMed · DOI
8Novo Nordisk. Awiqli prescribing information / SmPC (current label). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

31 Oct 2026Profile published — awaiting medical review

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