Insulin aspart

Insulin aspart, sold under the brand name NovoLog and Fiasp, among others, is a modified type of medical insulin used to treat type 1 and type 2 diabetes.[15] It is generally used by injection under the skin but may also be used by injection into a vein.[15] Maximum effect occurs after about 1–3 hours and lasts for 3–5 hours.[15] Generally a longer-acting insulin like insulin NPH is also needed.[15]

Insulin aspart
Clinical data
Trade namesNovoLog, NovoRapid, Fiasp, others
BiosimilarsKirsty,[1] Trurapi, Truvelog[2]
AHFS/Drugs.comMonograph
MedlinePlusa605013
License data
Pregnancy
category
Routes of
administration		Subcutaneous, intravenous
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC256H381N65O79S6
Molar mass5825.60 g·mol−1
 NY (what is this?)  (verify)

Common side effects include low blood sugar, allergic reactions, itchiness, and pain at the site of injection.[15] Other serious side effects may include low blood potassium.[15] Use in pregnancy and breastfeeding is generally safe.[3] It works the same as human insulin by increasing the amount of glucose that tissues take in and decreasing the amount of glucose made by the liver.[15] It is a manufactured form of human insulin; where a single amino acid has been changed, specifically a proline with an aspartic acid at the B28 position.[16]

Insulin aspart was approved for medical use in the United States in 2000.[15] In 2020, it was the 80th most commonly prescribed medication in the United States, with more than 9 million prescriptions.[17][18] Manufacturing involves yeast, which have had the gene for insulin aspart put into their genome.[19] This yeast then makes the insulin, which is harvested from the bioreactor.[20]

Medical uses

As of 2018, there is a lack of compelling evidence to conclude superiority of insulin aspart over human insulin in type 2 DM.[21] It is thus unclear why the shifting of people from human insulin to insulin aspart has occurred.[22] In type 1 DM it appears to result in slightly better blood sugar control.[23]

Onset of action

The onset of action is approximately fifteen minutes, the peak action is reached in 45–90 minutes, and the duration is 3–5 hours. However, as with all insulin, these numbers are based on averages, and vary between individuals due to blood flow, injection site, temperature and exercise.[24][25]

Side effects

The safety of insulin aspart in people with diabetes is no different from for regular insulin. The side effects that are commonly associated with insulin therapy include: allergic reactions, injection site irritation, rashes, and hypoglycemia.[26] The most common side effect is hypoglycemia. Long-term use of insulin, including insulin aspart, can cause lipodystrophy at the site of repeated injections or infusion. To reduce the risk of lipodystrophy, rotate the injection sites within the same region. Weight gain can also occur with the use of insulin aspart and it has been attributed to anabolic effects of insulin and a decrease in glucosuria. Use of insulin aspart has also been associated with sodium retention and edema.[27]

Chemical properties

The components of insulin aspart are as follows:

  • Metal ion – zinc (19.6 μg/mL)
  • Buffer – disodium hydrogen phosphate dihydrate (1.25 mg/mL)
  • Preservatives – 3-methylphenol (m-cresol) (1.72 mg/mL) and phenol (1.50 mg/mL)
  • Isotonicity agents – glycerin (16 mg/mL) and sodium chloride (0.58 mg/mL).

The pH of insulin aspart is 7.2–7.6.[24]

Formulations

Insulin aspart can be used in an insulin pump and insulin pen for subcutaneous injection. Additionally, it can be used with an injection port such as the I-port.[28]

Insulin aspart has a more rapid onset, and a shorter duration of activity than normal human insulin. Therefore, insulin aspart given by injection should normally be used in a regimen with long-acting or intermediate insulin.[29] Insulin aspart can also be used with external insulin pumps. The insulin in reservoirs of insulin pumps and infusion sets should be changed every 48 hours to avoid insulin degradation and loss of preservative.[25]

This is a picture of an insulin aspart injection (NovoLog brand) along with its packaging.

Temperature

It has been debated whether or not insulin aspart should be kept refrigerated at all times. The manufacturer claims it can last 28 days without refrigeration, as long as it is kept below 86 °F / 30 °C.[30] Above these temperatures, the potency of the insulin quickly degrades, rendering it less effective.

Variations

NovoLog Mix 70/30 is a product which contains 30% insulin aspart and 70% insulin aspart protamine. The insulin aspart protamine portion is a crystalline form of insulin aspart, which delays the action of the insulin, giving it a prolonged absorption profile after injection. The combination of the fast-acting form and the long-acting form allows the patient to receive fewer injections over the course of the day.[31]

The components of NovoLog Mix 70/30 are as follows:

  • Metal ion – zinc (19.6 μg/mL)
  • Buffer – dibasic sodium phosphate (1.25 mg/mL)
  • Preservatives – m-cresol (1.72 mg/mL) and phenol (1.50 mg/mL)
  • Isotonicity agents – sodium chloride (0.58 mg/mL) and mannitol (36.4 mg/mL)
  • Modifying protein – protamine (0.33 mg/mL)

The pH is 7.2–7.44.[24]

NovoLog Mix is marketed to be used with the Novo Nordisk FlexPen.[32] The onset of action is less than 30 minutes, the peak action is reached in 1–4 hours, and the duration is less than 24 hours.[24] NovoLog Mix is marketed in some countries as NovoMix 30.[33][13]

NovoRapid is produced in Saccharomyces cerevisiae by recombinant DNA technology.[9]

Biosimilars

On 10 December 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Kixelle, intended for the treatment of diabetes mellitus.[34] The applicant for this medicinal product is Mylan IRE Healthcare Limited. Kixelle was approved for medical use in the European Union in February 2021.[35] Kixelle was renamed to Kirsty.[1]

Trurapi was approved for medical use in Canada in October 2020.[36]

Truvelog and Truvelog Solostar were approved for medical use in Australia in October 2020.[2][6]

In October 2021, Kirsty was approved for medical use in Canada.[37]

On 24 February 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Truvelog Mix 30, intended for the treatment of diabetes mellitus.[38] The applicant for this medicinal product is sanofi-aventis groupe.[38] It was approved for medical use in the European Union in April 2022.[14]

References
  1. "Kirsty EPAR". European Medicines Agency (EMA). Archived from the original on 15 September 2021. Retrieved 14 September 2021.
  2. "Truvelog". Therapeutic Goods Administration (TGA). 23 October 2020. Archived from the original on 13 June 2021. Retrieved 12 June 2021.
  3. "Insulin aspart Pregnancy and Breastfeeding Warnings". Drugs.com. Archived from the original on 6 March 2019. Retrieved 3 March 2019.
  4. (PDF) https://web.archive.org/web/20210624194925/https://www.tga.gov.au/sites/default/files/auspar-insulin-aspart-200301.pdf. Archived from the original (PDF) on 24 June 2021. {{cite web}}: Missing or empty |title= (help)
  5. (PDF) https://web.archive.org/web/20220205044655/https://www.tga.gov.au/sites/default/files/auspar-insulin-aspart-rys-200827.pdf. Archived from the original (PDF) on 5 February 2022. {{cite web}}: Missing or empty |title= (help)
  6. "Truvelog Solostar ARTG". Therapeutic Goods Administration (TGA). Archived from the original on 13 June 2021. Retrieved 12 June 2021.
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  8. "Regulatory Decision Summary - Trurapi". Health Canada. 23 October 2014. Archived from the original on 5 June 2022. Retrieved 4 June 2022.
  9. "NovoRapid 100 units/ml in a vial - Summary of Product Characteristics (SmPC)". (emc). 25 May 2018. Archived from the original on 16 January 2021. Retrieved 9 September 2020.
  10. "Fiasp- insulin aspart injection injection, solution". DailyMed. 19 December 2019. Archived from the original on 13 November 2020. Retrieved 12 November 2020.
  11. "NovoLog- insulin aspart injection, solution Insulin Diluting Medium For NovoLog- water injection injection, solution". DailyMed. 15 November 2019. Archived from the original on 12 November 2020. Retrieved 12 November 2020.
  12. "NovoLog Mix 70/30- insulin aspart injection, suspension". DailyMed. 15 November 2019. Archived from the original on 29 September 2020. Retrieved 12 November 2020.
  13. "NovoMix EPAR". European Medicines Agency (EMA). Archived from the original on 13 April 2020. Retrieved 12 April 2020.
  14. "Truvelog Mix 30 EPAR". European Medicines Agency. 23 February 2022. Archived from the original on 17 June 2022. Retrieved 16 June 2022.
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  16. Turner JR (2010). New Drug Development: An Introduction to Clinical Trials: Second Edition. Springer Science & Business Media. p. 32. ISBN 9781441964182. Archived from the original on 20 April 2021. Retrieved 11 September 2020.
  17. "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
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  21. Fullerton B, Siebenhofer A, Jeitler K, Horvath K, Semlitsch T, Berghold A, Gerlach FM (December 2018). "Short-acting insulin analogues versus regular human insulin for adult, non-pregnant persons with type 2 diabetes mellitus". The Cochrane Database of Systematic Reviews. 12: CD013228. doi:10.1002/14651858.CD013228. PMC 6517032. PMID 30556900.
  22. Cohen D, Carter P (December 2010). "How small changes led to big profits for insulin manufacturers". BMJ. 341: c7139. doi:10.1136/bmj.c7139. PMID 21159773. S2CID 30709912. Archived from the original on 29 August 2021. Retrieved 29 November 2019.
  23. Fullerton B, Siebenhofer A, Jeitler K, Horvath K, Semlitsch T, Berghold A, et al. (June 2016). "Short-acting insulin analogues versus regular human insulin for adults with type 1 diabetes mellitus". The Cochrane Database of Systematic Reviews. 2019 (6): CD012161. doi:10.1002/14651858.CD012161. PMC 6597145. PMID 27362975.
  24. Crommelin DJA, Sindelar RD, Meibohm B. 2008. Pharmaceutical Biotechnology: Fundamentals and Applications. New York, NY: Informa Healthcare USA, Inc. p 270.
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  26. "Novolog: most FAQ". Archived from the original on 3 October 2011. Retrieved 18 April 2011.
  27. "Novolog: insulin aspart (rDNA origin) injection" (PDF). Novo Nordisk. Archived (PDF) from the original on 22 March 2011. Retrieved 18 April 2011.
  28. "Aspart insulin (rDNA origin) injection". Archived from the original on 10 June 2007. Retrieved 8 June 2007.
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  30. "insulin aspart Storage". Novolog.com. Archived from the original on 4 March 2016. Retrieved 23 April 2016.
  31. Rx List: NovoLog Mix 70/30. 6 August 2008. http://www.rxlist.com/novolog-mix-70-30-drug.htm Archived 20 April 2009 at the Wayback Machine
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  34. "Kixelle: Pending EC decision". European Medicines Agency (EMA). 10 December 2020. Archived from the original on 12 December 2020. Retrieved 12 December 2020.
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  38. "Truvelog Mix 30: Pending EC decision". European Medicines Agency. 24 February 2022. Archived from the original on 27 February 2022. Retrieved 27 February 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
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