Insulin lispro

Since expectations were not fully met after the introduction of human insulins in the 1980s (onset of action too late, duration of action too long, etc.), modified insulin analogs were developed at the end of the 1990s (Hürter 2013).

The first insulin analog was insulin lispro (Danne2016).

Insulin Lispro is a biochemically produced human insulin which, together with aspart and glulisine, belongs to the group of rapid-acting insulin analogues (Kasper 2015).

It came onto the market in 1996 as "Humalog" (Danne 2016), the further development, the ultra-short-acting insulin Ultra Rapid Lispro, in September 2020 (Jaursch-Hancke 2021).

Pharmacodynamics

In insulin lispro, the amino acid lysine and proline in the B-chain have been swapped using recombinant DNA technology. It has full biological activity and is less prone to self-aggregation, which in turn leads to a faster onset of action and a shorter duration of action (Kasper 2015).

In the further development of Lispro, the Ultra Rapid Lispro, the addition of citrate and treprostinil accelerated the onset of action even more by increasing the local vascular permeability through citrate and the absorption rate through treprostinil (Hubert 2020).

Indication

Lispro can be used to treat type 1 diabetes (Kaiserman 2017) or type 2 diabetes (Prinz 2012) such as in:

• SIT (supplementary insulin therapy [German Medical Association 2021]).
• Intensified insulin therapy (both ICT and insulin pump therapy).
• basic bolus concept (Alawi 2019)
• Ketoacidosis
• intensive therapy (Weihrauch 2020)

Insulin Lispro is approved for children, adolescents and adults ((Kaiserman 2017), the ultra-rapid Lyumjev so far only for adults (Fröhlich- Reiterer 2021).

Because lispro does not cross the placental barrier (Lapolla 2015), pregnant women can also be treated with it(Mader 2018)

Dosage and method of administration

The drug is usually administered s.c.. However, like insulin aspart, it is also approved for i.v. administration. This has no clinical advantage (Danne 2016), but it can be used to treat ketoacidosis or in intensive care therapy (Weihrauch 2020).

Lispro is also approved for i. m. injection, but this is not recommended (Weihrauch 2020).

Lispro can be injected just before (< 10 min) or just after a meal. The latter is particularly important for diabetics with gastroparesis or unpredictable food intake (Kasper 2015).

Advantages

• in most cases, intermediate meals can be dispensed with
• no or a short injection-meal interval is possible
• as well as the postprandial injection (Herold 2018).
• Hypoglycemia:

The number of hypoglycemias is lower than with normal insulin (Kasper 2015).

Compared with human insulin, nocturnal hypoglycemias occurred less frequently in children ( 8.5 vs. 13%) and adolescents (1.0 vs. 1.7 episodes within 30 days).

The risk of severe hypoglycemia is even significantly reduced - compared to human insulin (Kaiserman 2017).

• Improved quality of life for patients
• HbA1c- value:

According to Cochrane meta-analysis (2006), Lispro causes - compared to human insulin - a (small) reduction of the HbA1c- value (Kaiserman 2017).

• Diabetic ketoacidosis:

Very rare cases of diabetic ketoacidosis occurred during treatment with lispro (2% in a study by Weinzimer et al.)

• Lipodystrophy

Both atrophy and hypertrophy rarely occur during treatment with Lispro (Kaiserman 2017).

Disadvantages

• Need for precise dosing of basal insulin supply
• Duration of action may be too short with slowly absorbed carbohydrates (Herold 2018)
• Allergic reactions:

Antibody formation with Lispro is comparable to other insulins. Both Eapen et al. (2000) and Hasselmann et al. (2013) reported 3 cases in which allergic reactions to human insulin or NPH- insulinoccurred and improved after switching to insulin lispro (Kaiserman 2017).

Adverse effects

• Hypoglycemia
• Antibody formation (Kaiserman 2017)

Contraindication

Absolute Contraindications:

• Hypoglycemia
• Insulinoma (Flake 2021)

Preparations

• Insulin Lispro:

Trade names "Humalog" (Herold 2018) or "Liprolog" (Jaursch- Hancke 2021).

• Onset of action is 20 - 25 min, duration of action is 4 - 5 h (Haak 2018).
• Ultra Rapid Lispro:

Trade name "Lyumjev" (Jaursch- Hancke 2021).

Onset of action is 20 min, duration of action is 5 h (Lilly technical information).

• Insulin mixes such as:
  • Humalog Mix 25 (25 % insulin lispro and 75 % NPH insulin [Herold 2018])
  • Humalog Mix 50 (50 % insulin lispro and NPH insulin [Hoc 1999])

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