Insulin Icodec

Metabolic / Diabetes

Also known as: Awiqli, Once-Weekly Insulin, Novo Nordisk Weekly Insulin, NN1436

Basal Insulins (Ultra-Long-Acting)Research phase: FDA-approved (2024)Regulatory: FDA-approved May 2024 for type 1 and type 2 diabetes (Novo Nordisk, brand name Awiqli). EMA-approved. Once-weekly SubQ injection. Available by prescription. Covered by most insurance plans.

Mechanism

Insulin Icodec (brand name Awiqli) is a revolutionary once-weekly basal insulin — the first of its kind to receive FDA approval. Instead of daily injections, patients inject just once per week and get smooth, steady insulin coverage for 7 full days. This is possible because the insulin molecule has been engineered with a fatty acid side chain that binds tightly to albumin in the blood, creating a slow-release depot. Clinical trials showed it controls blood sugar as effectively as daily insulin glargine (Lantus) with the same safety profile.

Technical detail

Insulin icodec is a basal insulin analog engineered for once-weekly dosing. Structural modifications: (1) C20 icosanoic fatty diacid attached via a linker to LysB29, enabling strong reversible albumin binding (>99% bound) that dramatically extends half-life to ~196 hours (vs. ~24h for glargine); (2) Three amino acid substitutions (A14E, B16H, B25H) reduce insulin receptor binding affinity of the albumin-bound form while maintaining full activity of the free fraction. Pharmacokinetics: slow dissociation from albumin depot provides steady-state free insulin release over 7 days. At steady state (after 3-4 weekly doses), achieves flat PK/PD profile comparable to daily basal insulins. ONWARDS clinical trial program (6 Phase 3a trials, >4,000 patients): non-inferior to daily insulin glargine U100 for HbA1c reduction in T2D (ONWARDS 1,2,3,4) and T1D (ONWARDS 6). Comparable hypoglycemia rates. Time in range (CGM) equivalent to daily basal insulin.

Evidence

Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial.
Lingvay I, Asong M, Desouza C, Gourdy P, Kar S, Vianna A, et al. (2023) — JAMA — PMID: 37354562
Among 588 insulin-naive adults with type 2 diabetes, once-weekly insulin icodec achieved superior HbA1c reduction versus once-daily insulin degludec at 26 weeks (ETD -0.2 percentage points; 95% CI -0.3 to -0.1), with higher level 2/3 hypoglycemia in some analyses but fewer than 1 event per patient-year in both groups.
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Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5): A Randomized Trial.
Bajaj HS, Aberle J, Davies M, Donatsky AM, Frederiksen M, Yavuz DG, et al. (2023) — Annals of Internal Medicine — PMID: 37748181
In 1085 insulin-naive adults with type 2 diabetes, once-weekly insulin icodec plus a dosing app produced superior HbA1c reduction versus once-daily basal analogues at 52 weeks (ETD -0.38 percentage points; 95% CI -0.66 to -0.09), with improved treatment satisfaction and similarly low clinically significant or severe hypoglycemia.
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