Insulin-aspart

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 analogues were developed at the end of the 1990s (Hürter 2013). These include insulin aspart, which was launched on the market in 2000 (Heinemann 2001).

A further development of the insulin Aspart resulted in the insulin Faster Aspart. This has been on the market since April 2017 (Jaursch-Hancke 2021).

Insulin aspart (IAsp) is a recombinant analog of human insulin (Simpson 1999) produced synthetically using bacteria (Escherichia coli) and yeast (Saccharomyces cerevisiae) (Huismann 2005).

Insulin aspart (IAsp) belongs to the group of insulin analogs (Haak 2018). In the production of IAsp, the amino acid proline is exchanged for aspartic acid using genetic engineering (Zeeck 2017).

In addition to IAsp, there is also the insulin Faster Aspart, which is characterized by a more rapid onset of action (Haahr 2019). Faster aspart could be genetically modified (Kasper 2015) from IAsp by adding L-arginine and niacinamide (vitamin B3) in such a way that the onset of action is faster (Herold 2018).

Comparison of IAsp with human insulin:

• higher concentrations of serum insulin are achieved in a shorter period of time
• the decrease in serum insulin concentration is more rapid
• the control of glucose values during the day is more successful
• the minimum glucose values at night are not so low
• hypoglycemia occurs less frequently
• type 1 diabetics have fewer postprandial glucose excursions (Simpson 1999)
• IAsp does not need to be mixed thoroughly before injection (Herold 2018).

Pharmacodynamics

DNA- synthesis occurs in normal insulin exclusively via activation of the insulin receptor. In IAsp, however, signal induction by the IGF- I receptor plays an important role (Eckhardt 2007). A mitogenic effect feared as a result could not be confirmed so far (Haak 2018).

A variation of the amino acid sequence prevents the subcutaneous formation of hexamers in insulin aspart. This causes the more rapid absorption (Herold 2018). IAsp, like all short-acting insulin analogues, best mimics the physiological secretion of insulin in the first postprandial phase (Jahn 2020 / Rodbard 2020).

Indication

IAsp can be used in all forms of insulin therapy of type 1 diabetes or type 2 diabetes (Prinz 2012) such as:

- SIT (supplemental insulin therapy)

- Intensified insulin therapy (both ICT and insulin pump therapy [Herold 2020]).

- basic bolus concept (Alawi 2019)

- conventional insulin therapy (Greten 2005)

Dosage and mode of administration

IAsp can be administered by pen, pump, and closed-loop systems (Jahn 2020).

IAsp is usually administered s.c.. However, it is also approved for i.v. application, which does not provide any clinical advantage (Danne 2016).

Insulin aspart can be injected into the abdominal wall (faster absorption) and into the front or outer thigh (slower absorption).

(Schubert 2009)

Injection sites should be changed constantly to avoid lipohypertrophy (Marischler 2020).

In the case of aspartic mixed insulins, it is recommended that they be administered in the abdominal wall in the morning and in the thigh in the evening (Schubert 2009).

The daily insulin requirement of a healthy person is 0.67 I. E. / kg / d = approx. 40 I. E. Of this, about 40% is for basal secretion and about 60% for postprandial (Dellas 2018 / Seifert 2018).

Lowering blood glucose:

To achieve a reduction in blood glucose of 30 - 40 mg / dl (1.6 - 2.2 mmol / l), 1.0 I.U. normal ins ulin or rapid-acting analog insulin is required (Haak 2018).

For more details, see. Insulin

Raising blood glucose:

To achieve an elevation of blood glucose by 30 - 40 mg / dl (1.6 - 2.2 mmol / l), 10 g of carbohydrate = 1 KE is required (Haak 2018).

The size of the meal is measured in carbohydrate units = KE, the outdated term is bread unit = BE [Dellas 2018]) (Herold 2021).

A higher dose of insulin may be required, for example, for:

- Blood glucose > 270 mg / dl

- dehydration

- infections

- fever

- Detection of ketone bodies (Haak 2018).

A lower dose of insulin may be needed in cases such as:

- insufficiency of the adrenal cortex

- severe renalinsufficiency

- liver insufficiency

- physical stress (Haak 2018)

Adverse effects

- hypoglycemia

- Antibody formation is comparable to that with human insulin

Corresponding studies with regard to long-term damage are still pending (Mehnert 2003)

Contraindication

Absolute contraindications:

- hypoglycemia

- Insulinoma (Flake 2021)

Preparations

• Insulin Aspart (NovoRapid):

Onset of action with s. c. Injection occurs after 20 - 25 min, duration of action is 4 - 5 h (Haak 2018).

• Insulin Faster Aspart (Fiasp):

The onset of action is already after 4.9 min (Meißner 2021/ Haak 2018). The duration of action is approximately 3.5 h (Herold 2018).

Insulin Faster Aspart comes closest to the physiological secretion of insulin during a meal and thus improves postprandial glucose control in diabetics (Haahr 2019).

Premixed insulin analogues include:

• 70 / 30 Novolog / Novo Nordisk: 70% protamine-aspart, 30% aspart (Ferri 2021 / Hartman 2008). Onset of action after 20 - 25 min, duration of action 10 - 14 h (Haak 2018).

• Combination insulin degludec (70) / aspart (30) = IdegAsp.

IdegAsp is the first combination insulin of two insulin analogues. It provides both basal and mealtime insulin delivery with a single injection (Haahr 2017). The onset of action occurs after 20 - 25 min, and the duration of action is > 30 h (Haak 2018).

In a randomized controlled trial with 423 type 1 diabetics, treatment with aspart - compared to regular normal insulin - showed a significant improvement in HbA1c- value by 0.17%, an improvement in treatment satisfaction (p = 0.005) and a higher rated flexibility (p = 0.022).

In another study, significant improvements in clinical effects such as on hypoglycemia, blood glucose, treatment satisfaction were recorded (Haak 2018).

In patients with type 1 diabetes, the faster insulin aspart leads to a greater reduction in HbA1c compared to IAsp. These differences were not found in type 2 diabetics(Davis 2019).

Insulin analogs were compared to other insulin preparations in a large study:

• 1st aspart / insulin detemir with NPH insulin / regular- insulin:

The mean HbA1c in the aspart/detemir group was 7.88%, lower than in the NPH/regular-insulin groupwith 8.11% (Hartman 2008).

1. Alawi H et al (2019) Insulin types and insulin action. Ascensia DiabetesCollege Advisory Board 2019.
2. Bahrmann A et al. (2018) S2k-guideline diagnostics, therapy and follow-up of diabetes mellitus in old age. 2nd edition AWMF Register Number: 057-017.
3. German Medical Association (2021) National health care guidelines: type 2- diabetes. AWMF- Register- No. nvl-001.
4. Danne T et al (2016) Compendium of pediatric diabetology. Springer Verlag Berlin / Heidelberg 111
5. Davis A et al. (2019) Faster insulin aspart: A New Bolus Option for Diabetes Mellitus. Clin Pharmacokinet. 58 (4) 421 - 430
6. Dellas C (2018) Short textbook pharmacology. Elsevier Urban and Fischer Publishers Munich 155, 506 - 510, 512.
7. Eckhardt K et al (2007) The mitogenic effect of insulin analogues is determined by the expression level of the IGF-I receptor in human smooth muscle cells and fibroblasts. Diabetology and Metabolism (2) 129
8. Egidi G (2019) What is the place of insulin analogues In the treatment of diabetes? ZFA (95) 360 - 365. doi10.3238/zfa.2019.0360-0365.
9. Flake F et al (2021) Emergency medications. Elsevier Urban and Fischer Publishers 157 - 158.
10. Ferri F F (2021) Ferri's Clinical Advisor: 5 books in 1.Elsevier Urabn and Fischer Publishers 505, 508.
11. Greten H et al (2005) Internal medicine. Georg Thieme Verlag Stuttgart 624
12. Haahr H et al. (2017) A Review of Insulin Degludec/Insulin Aspart: Pharmacokinetic and Pharmacodynamic Properties and Their Implications in Clinical Use. Clin Pharmacokinet. 56 (4) 339 - 354
13. Haahr H (2019) Fast-Acting Insulin Aspart: A Review of its Pharmacokinetic and Pharmacodynamic Properties and the Clinical Consequences. Clin Pharmacokinet (59) 155 - 172
14. Haak T et al (2018) S3 guideline therapy of type 1 diabetes. AWMF Register Number: 057-013.
15. Hartman I (2008) Insulin analogs: impact on treatment success, satisfaction, quality of life, and adherence. Clin Med Res. 6 (2) 54 - 67.
16. Heinemann L et al (2001) Clinical effects and pharmacodynamics of the insulin analogues lispro, aspart, and glargine. Dtsch Med Wschr (126) 597 - 604.
17. Herold G et al (2020) Internal Medicine. Herold Publishers 737
18. Hürter P et al (2013) Diabetes in children and adolescents: clinic - therapy - rehabilitation. Springer Verlag Berlin / Heidelberg 103
19. Jahn E (2020) Modern insulin analogues. CME (17) 54 https://doi.org/10.1007/s11298-020-8134-2.
20. Jaursch- Hancke C (2021) 100 years of insulin - the road to physiology. InFo Diabetology 15 (4) 32 - 34.
21. Kasper D L et al (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 2412 - 2413.
22. Marischler (2020) Endocrinology: basics. Elsevier Urban and Fischer Publishers Munich 37
23. Mehnert H et al (2003) Diabetology in clinic and practice. Georg Thieme Verlag Stuttgart 244
24. Meißner T (2021) Type 1 diabetes: progress with insulin analogues. CME issue 7 - 8. 12
25. Prinz C et al (2012) Basic knowledge of internal medicine. Springer Verlag Heidelberg 296 - 298
26. Rodbard H W et al (2020) Biosynthetic human insulin and insulin analogs. Am J Ther. 27 (1) e42 - e51 DOI: 10.1097/MJT.00000000001089.
27. Schubert I et al. (2009) Guideline group Hesse / PMV research group: family physician guidelines. Deutscher Ärzteverlag Cologne 152
28. Seifert R (2018) Basic knowledge of pharmacology. Springer Verlag Berlin / Heidelberg 247
29. Simpson K L et al (1999) Insulin aspart. Drugs 57 (5) 759 - 765
30. Zeeck A et al (2017) Chemistry for physicians. Elsevier Urban and Fischer Publishers 374