Insulin analogue

An insulin analogue (also called an insulin analog) is a type of medical insulin that has been modified to alter its pharmacokinetic properties while maintaining the same biological function as human insulin.[2] These modifications are achieved through genetic engineering,[3] which allows for changes in the amino acid sequence of insulin to optimize its absorption, distribution, metabolism, and excretion (ADME) characteristics.[4]

All insulin analogues work by enhancing glucose uptake in tissues and reducing glucose production by the liver.[5] They are prescribed for conditions such as type 1 diabetes, type 2 diabetes,[6] gestational diabetes, and diabetes-related complications such as diabetic ketoacidosis.[6] Additionally, insulin is sometimes administered alongside glucose to treat elevated blood potassium levels (hyperkalemia).[7]

Insulin analogues are classified based on their duration of action. Short-acting (bolus) insulin analogues, such as insulin lispro, insulin aspart, and insulin glulisine,[8] have been designed to be absorbed quickly, mimicking the natural insulin response after meals. Long-acting (basal) insulin analogues, including insulin glargine, insulin detemir,[8] and insulin degludec, provide a sustained release of insulin to maintain basal blood glucose levels over an extended period. These modifications enhance the predictability of insulin therapy and reduce the risk of hypoglycemia compared to regular human insulin.[9]

Lispro, the first insulin analogue, was approved in 1996.[10] This was followed by an influx of new analogues with differing pharmacokinetic properties. The first long-acting analogue, insulin glargine, was approved in 2000. Insulin aspart, insulin glulisine, and insulin detemir were all approved by 2005.[10] The second wave of insulin analogues, which include insulin degludec[11] and insulin icodec,[12] started in the mid-2010s.[13]

  1. ^ Brateanu A, Russo-Alvarez G, Nielsen C (2015). "Starting insulin in patients with type 2 diabetes: An individualized approach". Cleveland Clinic Journal of Medicine. 82 (8): 513–519. doi:10.3949/ccjm.82a.14069. PMID 26270430. Retrieved 24 February 2025.
  2. ^ McDermott MT (2009). Endocrine secrets. Secrets series (5th ed.). Philadelphia, PA: Mosby/Elsevier. ISBN 978-0-323-05885-8.
  3. ^ Mayer JP, Zhang F, DiMarchi RD (January 2007). "Insulin structure and function". Biopolymers. 88 (5): 687–713. doi:10.1002/bip.20734. ISSN 0006-3525. PMID 17410596.
  4. ^ Hirsch IB (13 January 2005). "Insulin Analogues". The New England Journal of Medicine. 352 (2): 174–183. doi:10.1056/NEJMra040832. ISSN 0028-4793. PMID 15647580.
  5. ^ Cite error: The named reference Mathieu_2017 was invoked but never defined (see the help page).
  6. ^ a b "Insulin Analogs". Diabetes Teaching Center. University of California San Francisco. Retrieved 10 March 2025.
  7. ^ Mahoney BA, Smith WA, Lo D, Tsoi K, Tonelli M, Clase C (20 April 2005). "Emergency interventions for hyperkalaemia". The Cochrane Database of Systematic Reviews. 2005 (2). Wiley: CD003235. doi:10.1002/14651858.cd003235.pub2. ISSN 1465-1858. PMC 6457842. PMID 15846652.
  8. ^ a b Hartman I (7 July 2008). "Insulin Analogs: Impact on Treatment Success, Satisfaction, Quality of Life, and Adherence". Clinical Medicine & Research. 6 (2): 54–67. doi:10.3121/cmr.2008.793. ISSN 1539-4182. PMC 2572551. PMID 18801953.
  9. ^ Burge MR, Rassam AG, Schade DS (1 October 1998). "Lispro Insulin: Benefits and Limitations". Trends in Endocrinology and Metabolism: TEM. 9 (8): 337–341. doi:10.1016/S1043-2760(98)00083-6. PMID 18406299.
  10. ^ a b Quianzon CC, Cheikh I (January 2012). "History of insulin". Journal of Community Hospital Internal Medicine Perspectives. 2 (2): 18701. doi:10.3402/jchimp.v2i2.18701. ISSN 2000-9666. PMC 3714061. PMID 23882369.
  11. ^ Haahr H, Heise T (September 2014). "A review of the pharmacological properties of insulin degludec and their clinical relevance". Clinical Pharmacokinetics. 53 (9): 787–800. doi:10.1007/s40262-014-0165-y. PMC 4156782. PMID 25179915.
  12. ^ 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.
  13. ^ "Tresiba (insulin degludec) FDA Approval History". Drugs.com. Retrieved 10 March 2025.
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