Insulin lispro

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Insulin lispro
Insulin lispro dodecamer 6NWV.png
Clinical data
Trade namesHumalog, Liprolog, Admelog, others
Other namesURLi, LY900014, LY-275585, insulin lispro-aabc
License data
Routes of
ATC code
Legal status
Legal status
  • UK: POM (Prescription only) [2]
  • US: ℞-only
  • EU: Rx-only
  • In general: ℞ (Prescription only)
CAS Number
PubChem CID
  • none
CompTox Dashboard (EPA)
Chemical and physical data
Molar mass5813.68 g·mol−1
3D model (JSmol)
  • InChI=1S/C158H234N40O42S2.C99H155N25O35S4/c1-79(2)57-104(181-131(213)86(15)173-136(218)102(50-53-125(211)212)179-152(234)127(84(11)12)194-148(230)107(60-82(7)8)184-145(227)113(67-95-70-166-78-172-95)189-150(232)115(74-199)176-123(208)73-170-134(216)116(75-241)191-140(222)105(58-80(3)4)182-144(226)112(66-94-69-165-77-171-94)188-138(220)101(48-51-119(161)204)178-146(228)114(68-120(162)205)190-153(235)126(83(9)10)193-132(214)98(160)61-89-31-21-18-22-32-89)139(221)185-110(64-92-40-44-96(202)45-41-92)142(224)183-106(59-81(5)6)147(229)195-128(85(13)14)154(236)192-117(76-242)135(217)169-71-121(206)174-100(49-52-124(209)210)137(219)177-99(38-29-55-167-158(163)164)133(215)168-72-122(207)175-108(62-90-33-23-19-24-34-90)141(223)186-109(63-91-35-25-20-26-36-91)143(225)187-111(65-93-42-46-97(203)47-43-93)149(231)196-129(87(16)200)155(237)180-103(37-27-28-54-159)156(238)198-56-30-39-118(198)151(233)197-130(88(17)201)157(239)240;1-12-46(9)77(121-73(134)36-100)97(156)122-76(45(7)8)95(154)108-56(25-29-75(137)138)80(139)105-54(23-27-70(102)131)83(142)117-66(40-161)93(152)119-68(42-163)94(153)124-79(48(11)127)98(157)116-64(38-126)90(149)123-78(47(10)13-2)96(155)120-67(41-162)92(151)115-63(37-125)89(148)110-58(31-44(5)6)85(144)111-59(32-49-14-18-51(128)19-15-49)86(145)106-53(22-26-69(101)130)81(140)109-57(30-43(3)4)84(143)107-55(24-28-74(135)136)82(141)113-61(34-71(103)132)88(147)112-60(33-50-16-20-52(129)21-17-50)87(146)118-65(39-160)91(150)114-62(99(158)159)35-72(104)133/h18-26,31-36,40-47,69-70,77-88,98-118,126-130,199-203,241-242H,27-30,37-39,48-68,71-76,159-160H2,1-17H3,(H2,161,204)(H2,162,205)(H,165,171)(H,166,172)(H,168,215)(H,169,217)(H,170,216)(H,173,218)(H,174,206)(H,175,207)(H,176,208)(H,177,219)(H,178,228)(H,179,234)(H,180,237)(H,181,213)(H,182,226)(H,183,224)(H,184,227)(H,185,221)(H,186,223)(H,187,225)(H,188,220)(H,189,232)(H,190,235)(H,191,222)(H,192,236)(H,193,214)(H,194,230)(H,195,229)(H,196,231)(H,197,233)(H,209,210)(H,211,212)(H,239,240)(H4,163,164,167);14-21,43-48,53-68,76-79,125-129,160-163H,12-13,22-42,100H2,1-11H3,(H2,101,130)(H2,102,131)(H2,103,132)(H2,104,133)(H,105,139)(H,106,145)(H,107,143)(H,108,154)(H,109,140)(H,110,148)(H,111,144)(H,112,147)(H,113,141)(H,114,150)(H,115,151)(H,116,157)(H,117,142)(H,118,146)(H,119,152)(H,120,155)(H,121,134)(H,122,156)(H,123,149)(H,124,153)(H,135,136)(H,137,138)(H,158,159)/t86-,87+,88+,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,126-,127-,128-,129-,130-;46-,47-,48+,53-,54-,55-,56-,57-,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,68-,76-,77-,78-,79-/m00/s1
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Insulin lispro, sold under the brand name Humalog among others, is a modified type of medical insulin used to treat type 1 and type 2 diabetes.[3] Typically it is taken around the time of eating.[3] It is used by injection under the skin or within an insulin pump.[3][4] Onset of effects typically occurs within 30 minutes and lasts about 5 hours.[3] Often a longer-acting insulin like insulin NPH is also needed.[3]

Common side effects include low blood sugar.[3] Other serious side effects may include low blood potassium.[3] Use in pregnancy and breastfeeding is generally safe.[5] 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.[3]

Insulin lispro was first approved for use in the United States in 1996.[3][6][7] It is a manufactured form of human insulin where an amino acid has been switched.[8] In 2019, it was the 65th most commonly prescribed medication in the United States, with more than 11 million prescriptions.[9][10]

Medical uses[edit]

Insulin lispro is used to treat people with type 1 diabetes or type 2 diabetes.[3] People doing well on regular insulin should not generally be changed to insulin lispro.[3]

Side effects[edit]

Common side effects include skin irritation at the site of injection, hypoglycemia, hypokalemia, and lipodystrophy.[6] Other serious side effects include anaphylaxis, and hypersensitivity reactions.[6]


Do not administer insulin lispro during episodes of hypoglycemia, or if a person has a hypersensitivity to insulin lispro or any of its excipients.[6]

Mechanism of action[edit]

Through recombinant DNA technology, the final lysine and proline residues on the C-terminal end of the B-chain are reversed. This modification does not alter receptor binding, but blocks the formation of insulin dimers and hexamers. This allows larger amounts of active monomeric insulin to be immediately available for postprandial injections.[11]


It is a manufactured form of human insulin where the amino acids lysine and proline have been switched at the end of the B chain of the insulin molecule.[8] This switch of amino acids mimics Insulin-like growth factor 1 which also has lysine (K) and proline (P) in that order at positions 27 and 28.[12]


In the United States, the price of for a vial of Humalog increased from US$35 in 2001 to US$234 2015,[13] or US$10.06 and US$29.36 per 100 units.[14] In April 2019, Eli Lilly and Company announced they would produce a version selling for US$137.35 per vial, about half the then-current cost. The chief executive said that this was a contribution "to fix the problem of high out-of-pocket costs for Americans living with chronic conditions", but Patients for Affordable Drugs Now said this was just a public relations move, as "other countries pay US$20 for a vial of insulin."[13]

The cost in the United Kingdom was between £1.66 and £1.96 per 100 units, in 2017.[15]


Insulin lispro (brand name Humalog) was granted marketing authorization in the European Union in April 1996,[16] and it was approved for use in the United States in June 1996.[7][17]

Insulin lispro (brand name Liprolog) was granted marketing authorization in the European Union in May 1997,[18] and again in August 2001.[19]

Combination drugs combining insulin lispro and other forms of insulin were approved for use in the United States in December 1999.[20][21][22]

Insulin lispro Sanofi was granted marketing authorization as a biosimilar in the European Union in July 2017.[23]

Insulin lispro injection (brand name Admelog) was approved for use in the United States in December 2017.[24][25][26]

In January 2020, the Committee for Medicinal Products for Human Use (CHMP) in the European Union recommended granting of a marketing authorization for insulin lispro acid (brand name Lyumjev) for the treatment of diabetes mellitus in adults.[27][28] Insulin lispro (Lyumjev) was approved for use in the European Union in March 2020, and in the United States on 18 June 2020 as reported by Medscape.[29]


  1. ^ "Insulin lispro Use During Pregnancy". 7 October 2019. Retrieved 23 February 2020.
  2. ^ "Humalog 100 units/ml, solution for injection in vial - Summary of Product Characteristics (SmPC)". (emc). 30 January 2020. Retrieved 23 February 2020.
  3. ^ a b c d e f g h i j k "Insulin Lispro Monograph for Professionals". American Society of Health-System Pharmacists. Retrieved 3 March 2019.
  4. ^ British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 698. ISBN 9780857113382.
  5. ^ "Insulin lispro Pregnancy and Breastfeeding Warnings". Retrieved 3 March 2019.
  6. ^ a b c d "Humalog- insulin lispro injection, solution Humalog Kwikpen- insulin lispro injection, solution Humalog Junior Kwikpen- insulin lispro injection, solution Humalog Tempo Pen- insulin lispro injection, solution". DailyMed. 25 November 2019. Retrieved 23 February 2020.
  7. ^ a b "Humalog approval" (PDF). U.S. Food and Drug Administration (FDA). 14 June 1996. Retrieved 23 February 2020.
  8. ^ a b Koivisto VA (June 1998). "The human insulin analogue insulin lispro". Annals of Medicine. 30 (3): 260–6. doi:10.3109/07853899809005853. PMID 9677011.
  9. ^ "The Top 300 of 2019". ClinCalc. Retrieved 16 October 2021.
  10. ^ "Insulin Lispro - Drug Usage Statistics". ClinCalc. Retrieved 16 October 2021.
  11. ^ Noble SL, Johnston E, Walton B (January 1998). "Insulin lispro: a fast-acting insulin analog". American Family Physician. 57 (2): 279–86, 289–92. PMID 9456992.
  12. ^ Ratledge, C., & Kristiansen, B. (2007). Basic biotechnology. Cambridge: Cambridge University Press. Page 513 "insulin lispro, where, in analogy to the naturally occur- ring insulin homologue insulin-like growth factor-I (IGF-I), the order of the amino acid residues B28 and B29 was changed;"
  13. ^ a b Sullivan, Peter (3 April 2019). "Drug company announces new version of insulin at half the price". The Hill. Retrieved 15 April 2019.
  14. ^ Langreth R (29 June 2016). "Decoding Big Pharma's Secret Drug Pricing Practices". Bloomberg. Retrieved 15 July 2016.
  15. ^ "Humalog". MIMS. Retrieved 12 January 2017.
  16. ^ "Humalog EPAR". European Medicines Agency (EMA). 11 February 2020. Retrieved 23 February 2020.
  17. ^ "Humalog: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 23 February 2020.
  18. ^ "Liprolog EPAR". European Medicines Agency (EMA). 1 August 2001. Retrieved 23 February 2020.
  19. ^ "Liprolog EPAR". European Medicines Agency (EMA). 11 February 2020. Retrieved 23 February 2020.
  20. ^ "Drug Approval Package: Humalog Mix (75/25 & 50/50) NDA# 21-017 & 21-018". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 23 February 2020.
  21. ^ "Humalog Mix50/50- insulin lispro injection, suspension Humalog Mix50/50 Kwikpen- insulin lispro injection, suspension". DailyMed. 19 November 2019. Retrieved 23 February 2020.
  22. ^ "Humalog Mix75/25- insulin lispro injection, suspension Humalog Mix75/25 Kwikpen- insulin lispro injection, suspension". DailyMed. 3 February 2020. Retrieved 23 February 2020.
  23. ^ "Insulin lispro Sanofi EPAR". European Medicines Agency (EMA). 17 June 2019. Retrieved 23 February 2020.
  24. ^ "Drug Approval Package: Admelog (insulin lispro)". U.S. Food and Drug Administration (FDA). 17 May 2018. Retrieved 23 February 2020.
  25. ^ "FDA Approves Sanofi's Admelog (insulin lispro injection) - Dec 11, 2017". Sanofi (Press release). 11 December 2017. Retrieved 23 February 2020.
  26. ^ "FDA approves Admelog, the first short-acting "follow-on" insulin product to treat diabetes". U.S. Food and Drug Administration (FDA) (Press release). 11 December 2017. Retrieved 12 December 2017.
  27. ^ "Lyumjev: Pending EC decision". European Medicines Agency (EMA). 30 January 2020. Retrieved 23 February 2020.{{cite web}}: CS1 maint: url-status (link)
  28. ^ "CHMP Recommends Approval of Lilly's New Fast-Acting Mealtime Insulin to Improve Glycemic Control in Adults with Diabetes". Eli Lilly and Company (Press release). 31 January 2020. Retrieved 23 February 2020.
  29. ^ "Ljumjev EPAR". European Medicines Agency (EMA). 29 January 2020. Retrieved 16 April 2020.{{cite web}}: CS1 maint: url-status (link)

External links[edit]