Pharmacodynamics
In normal insulin, DNA synthesis occurs exclusively via activation of the insulin receptor. In contrast, signal induction by the IGF-I receptor plays an important role in insulin analogs (Eckhardt 2007).
A mitogenic effect feared as a result has not yet been confirmed (Haak 2018).
- Short-acting insulin analogues:
Here, a variation of the amino acid sequence prevents the subcutaneous formation of hexamers. This causes the more rapid absorption (Herold 2018). Short-acting insulin analogues best mimic the physiological secretion of insulin in the first postprandial phase (Jahn 2020 / Rodbard 2020).
- Long-acting insulin analogues:
By changing the insulin structure, a significant prolongation of the duration of action is achieved, which is usually between 20 - 28 h (Herold 2018).
In the case of the particularly long-acting insulin Degludec, the effect sets in after 0.5 - 1.5 h and even lasts up to 42 h (Meißner 2021).
Indication
Insulin analogues can be used in all forms of insulin therapy for type 1 or type 2 diabetes (Prinz 2012) such as:
Dosage and type of application
Mode of administration:
Insulin analogues can be administered by pen, pump, and closed-loop systems (Jahn 2020).
Insulin analogues are administered s. c. Short-acting insulin analogues such as aspart, glulisine, and lispro are also approved for i.v. administration, but this does not provide any clinical advantage (Danne 2016).
Short-acting insulin analogues should be injected into the abdominal wall (faster absorption) and long-acting ones into the front or outer thigh. For mixed insulins, it is recommended to inject into the abdominal wall in the morning and into the thigh in the evening (Schubert 2009).
Dosage
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). For more details, see. Insulin
Lowering blood glucose:
To achieve a decrease in blood glucose of 30 - 40 mg / dl (1.6 - 2.2 mmol / l), 1.0 I.U. normal insulin or rapid-acting analog insulin is required (Haak 2018).
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The size of the meal is measured in carbohydrate units = KE, the outdated term is bread unit = BE [Dellas 2018]) (Herold 2021).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)
Advantages
- Short-acting insulin analogues:
- Low risk of nocturnal hypoglycemia (e.g., for glargine P = 0.00003 or detemir P < 0.00001)
- Low mean incidence of severe hypoglycemia (21.8 per 100 person-years; with normal insulin, 46.1 per 100 person-years [Hartman 2008])
- less frequent occurrence of postprandial hypoglycemia
- in most cases it is possible to do without snacks between meals
- no or short injection-meal interval
- postprandial injection possible (Herold 2018)
- Long-acting insulin analogues:
- no strong maximum effect
- great temporal flexibility of the injection time (especially with insulin glargine) (Meißner 2021)
- fewer hypoglycemias due to the lack of a maximum effect (compared to, for example, protamine Hagedorn insulin)
- Less weight gain than with protamine hagedorn insulin [Tibaldi 2014]).
-
Detemir is the only insulin analog to show a weight-maintaining effect (Hartman 2008)
Disadvantages
- Short-acting insulin analogues:
- Need for exact dosing of basal insulin supply
- Effect may be too short with slowly absorbed carbohydrates (Herold 2018)
Contraindication
Absolute contraindications:
Preparations
Short-acting insulin analogues include:
- Insulin Aspart (NovoRapid) Onset of action after 20 - 25 min, duration of action 4 - 5 h (Haak 2018).
- Faster Aspart onset of action after 4.9 min (Meißner 2021/ Haak 2018), duration of action approx. 3.5 h (Herold 2018)
- Insulin- Glulisin (Apidra) Onset of action after 20 - 25 min, duration of action 4 - 5 h (Haak 2018)
- Insulin- Lispro (Humalog) Onset of action after 20 - 25 min, duration of action 4 - 5 h (Haak 2018).
(Herold 2018)
Long-acting insulin analogues include:
-
Insulin Detemir (Levemir) Onset of action after 1 h, duration of action 19 -26 h (Haak 2018).
-
Insulin Glargine (biosimilar Abasaglar , Lantus) Glargine U100: onset of action after 1 h, duration of action 20 - 27 h; Glargine U300: onset of action after 1 - 6 h, duration of action 30 - 32 h (Haak 2018) (Haak 2018).
(Herold 2018)
- Insulin Degludec (Tresiba) onset of action after 1 - 2 h, duration of action > 42 h (Haak 2018).
Premixed insulin analogs include:
- 75 / 25 Humalog / Eli Lilly: 75% neutral protamine- lispro, 25% lispro.
- 50 / 50 Humalog / Eli Lilly: 50 % neutral protamine- lispro, 50 % lispro
- 70 / 30 Novolog / Novo Nordisk: 70 % protamine aspart, 30 % aspart (Ferri 2021 / Hartman 2008)
For premixed insulin analogues: onset of action after 20 - 25 min, duration of action 10 - 14 h (Haak 2018).
- Combination insulin Degludec (70) / Aspart (30).
For combination insulin: onset of action after 20 - 25 min, duration of action > 30 h (Haak 2018).