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It has a plasma half-life more than eight days<ref>{{Cite journal |last=Kjeldsen |first=Thomas B. |last2=Hubálek |first2=František |last3=Hjørringgaard |first3=Claudia U. |last4=Tagmose |first4=Tina M. |last5=Nishimura |first5=Erica |last6=Stidsen |first6=Carsten E. |last7=Porsgaard |first7=Trine |last8=Fledelius |first8=Christian |last9=Refsgaard |first9=Hanne H. F. |last10=Gram-Nielsen |first10=Sanne |last11=Naver |first11=Helle |last12=Pridal |first12=Lone |last13=Hoeg-Jensen |first13=Thomas |last14=Jeppesen |first14=Claus Bekker |last15=Manfè |first15=Valentina |date=2021-07-08 |title=Molecular Engineering of Insulin Icodec, the First Acylated Insulin Analog for Once-Weekly Administration in Humans |url=https://pubmed.ncbi.nlm.nih.gov/33944562 |journal=Journal of Medicinal Chemistry |volume=64 |issue=13 |pages=8942–8950 |doi=10.1021/acs.jmedchem.1c00257 |issn=1520-4804 |pmid=33944562}}</ref> (compared to 25 hours of the previous longest-acting insulin analogue [[insulin degludec]]), making it a once-weekly basal insulin.<ref>{{cite journal | vauthors = Kjeldsen TB, Hubálek F, Hjørringgaard CU, Tagmose TM, Nishimura E, Stidsen CE, Porsgaard T, Fledelius C, Refsgaard HH, Gram-Nielsen S, Naver H, Pridal L, Hoeg-Jensen T, Jeppesen CB, Manfè V, Ludvigsen S, Lautrup-Larsen I, Madsen P | display-authors = 6 | title = Molecular Engineering of Insulin Icodec, the First Acylated Insulin Analog for Once-Weekly Administration in Humans | journal = Journal of Medicinal Chemistry | volume = 64 | issue = 13 | pages = 8942–8950 | date = July 2021 | pmid = 33944562 | doi = 10.1021/acs.jmedchem.1c00257 | s2cid = 233718893 }}</ref> The substance is composed of two peptide chains, linked by a disulfide bridge. In addition the 21 amino acid residue chain has two internal disulfide bridges and the second chain is 29 residues long.
It has a plasma half-life more than eight days<ref>{{Cite journal |last=Kjeldsen |first=Thomas B. |last2=Hubálek |first2=František |last3=Hjørringgaard |first3=Claudia U. |last4=Tagmose |first4=Tina M. |last5=Nishimura |first5=Erica |last6=Stidsen |first6=Carsten E. |last7=Porsgaard |first7=Trine |last8=Fledelius |first8=Christian |last9=Refsgaard |first9=Hanne H. F. |last10=Gram-Nielsen |first10=Sanne |last11=Naver |first11=Helle |last12=Pridal |first12=Lone |last13=Hoeg-Jensen |first13=Thomas |last14=Jeppesen |first14=Claus Bekker |last15=Manfè |first15=Valentina |date=2021-07-08 |title=Molecular Engineering of Insulin Icodec, the First Acylated Insulin Analog for Once-Weekly Administration in Humans |url=https://pubmed.ncbi.nlm.nih.gov/33944562 |journal=Journal of Medicinal Chemistry |volume=64 |issue=13 |pages=8942–8950 |doi=10.1021/acs.jmedchem.1c00257 |issn=1520-4804 |pmid=33944562}}</ref> (compared to 25 hours of the previous longest-acting insulin analogue [[insulin degludec]]), making it a once-weekly basal insulin.<ref>{{cite journal | vauthors = Kjeldsen TB, Hubálek F, Hjørringgaard CU, Tagmose TM, Nishimura E, Stidsen CE, Porsgaard T, Fledelius C, Refsgaard HH, Gram-Nielsen S, Naver H, Pridal L, Hoeg-Jensen T, Jeppesen CB, Manfè V, Ludvigsen S, Lautrup-Larsen I, Madsen P | display-authors = 6 | title = Molecular Engineering of Insulin Icodec, the First Acylated Insulin Analog for Once-Weekly Administration in Humans | journal = Journal of Medicinal Chemistry | volume = 64 | issue = 13 | pages = 8942–8950 | date = July 2021 | pmid = 33944562 | doi = 10.1021/acs.jmedchem.1c00257 | s2cid = 233718893 }}</ref> The substance is composed of two peptide chains, linked by a disulfide bridge. In addition the 21 amino acid residue chain has two internal disulfide bridges and the second chain is 29 residues long.


Glycemic control was significantly better with once-weekly insulin icodec than with once-daily insulin glargine U100. (Funded by Novo Nordisk; [https://clinicaltrials.gov/study/NCT04460885?cond=Diabetes%20Mellitus%20Type%202&term=Icodec&titles=ONWARDS%201&rank=1 ONWARDS 1] ClinicalTrials.gov number, NCT04460885. opens in new tab.)
Glycemic control was non-inferior with once-weekly insulin icodec compared with once-daily insulin glargine U100. (Funded by Novo Nordisk; [https://clinicaltrials.gov/study/NCT04460885?cond=Diabetes%20Mellitus%20Type%202&term=Icodec&titles=ONWARDS%201&rank=1 ONWARDS 1] ClinicalTrials.gov number, NCT04460885. opens in new tab.)


<ref>{{Cite journal |last=Rosenstock |first=Julio |last2=Bain |first2=Stephen C. |last3=Gowda |first3=Amoolya |last4=Jódar |first4=Esteban |last5=Liang |first5=Bo |last6=Lingvay |first6=Ildiko |last7=Nishida |first7=Tomoyuki |last8=Trevisan |first8=Roberto |last9=Mosenzon |first9=Ofri |date=2023-07-27 |title=Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin |url=https://www.nejm.org/doi/full/10.1056/NEJMoa2303208 |journal=New England Journal of Medicine |volume=389 |issue=4 |pages=297–308 |doi=10.1056/NEJMoa2303208 |issn=1533-4406 |pmid=37356066}}</ref>
<ref>{{Cite journal |last=Rosenstock |first=Julio |last2=Bain |first2=Stephen C. |last3=Gowda |first3=Amoolya |last4=Jódar |first4=Esteban |last5=Liang |first5=Bo |last6=Lingvay |first6=Ildiko |last7=Nishida |first7=Tomoyuki |last8=Trevisan |first8=Roberto |last9=Mosenzon |first9=Ofri |date=2023-07-27 |title=Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin |url=https://www.nejm.org/doi/full/10.1056/NEJMoa2303208 |journal=New England Journal of Medicine |volume=389 |issue=4 |pages=297–308 |doi=10.1056/NEJMoa2303208 |issn=1533-4406 |pmid=37356066}}</ref>

Revision as of 19:43, 17 August 2023

Insulin icodec
Clinical data
Trade namesAweeqli
Routes of
administration		subcutaneous
ATC code
Pharmacokinetic data
Elimination half-life196 hours
Identifiers
  • (1a-21a),(1b-29b)-Insulin (human), 14a-L-glutamic acid-16b-L-histidine-25b-L-histidine-29b-(N6-(N-(19-carboxy-1-oxononadecyl)-L-gamma-glutamyl-2-(2-(2-aminoethoxy)ethoxy)acetyl-2-(2-(2-aminoethoxy)ethoxy)acetyl)-L-lysine)-
CAS Number
DrugBank
UNII
KEGG

Insulin icodec (INN/USAN) is an ultralong-acting basal insulin analogue that was developed by Novo Nordisk under the brand name Aweeqli. It has completed Phase 3 trials[1] and has been submitted for regulatory review in the US, Canada, Europe, China, Australia, Switzerland and Brazil.[2] The first decisions are anticipated in H1 2024. It is administered via subcutaneous injection once weekly to help control the blood sugar level of those with diabetes.

It has a plasma half-life more than eight days[3] (compared to 25 hours of the previous longest-acting insulin analogue insulin degludec), making it a once-weekly basal insulin.[4] The substance is composed of two peptide chains, linked by a disulfide bridge. In addition the 21 amino acid residue chain has two internal disulfide bridges and the second chain is 29 residues long.

Glycemic control was non-inferior with once-weekly insulin icodec compared with once-daily insulin glargine U100. (Funded by Novo Nordisk; ONWARDS 1 ClinicalTrials.gov number, NCT04460885. opens in new tab.)

[5]

References

  1. ^ "Molecular and Biological Properties of Insulin Icodec*, a New Insulin Analog Designed to Give a Long Half-Life Suitable for Once-Weekly Dosing".
  2. ^ "News Details". Novo Nordisk. Retrieved 2023-07-24.
  3. ^ Kjeldsen, Thomas B.; Hubálek, František; Hjørringgaard, Claudia U.; Tagmose, Tina M.; Nishimura, Erica; Stidsen, Carsten E.; Porsgaard, Trine; Fledelius, Christian; Refsgaard, Hanne H. F.; Gram-Nielsen, Sanne; Naver, Helle; Pridal, Lone; Hoeg-Jensen, Thomas; Jeppesen, Claus Bekker; Manfè, Valentina (2021-07-08). "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. ISSN 1520-4804. PMID 33944562.
  4. ^ 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.
  5. ^ Rosenstock, Julio; Bain, Stephen C.; Gowda, Amoolya; Jódar, Esteban; Liang, Bo; Lingvay, Ildiko; Nishida, Tomoyuki; Trevisan, Roberto; Mosenzon, Ofri (2023-07-27). "Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin". New England Journal of Medicine. 389 (4): 297–308. doi:10.1056/NEJMoa2303208. ISSN 1533-4406. PMID 37356066.


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