Victoza

Victoza is an antidiabetic drug. Liraglutide is an analogue of the natural element GLP-1, which is produced using recombinant DNA biotechnology, which uses a strain of brewer's yeast, 97% homologous to human GLP-1. This component is synthesized and activates the endings of natural GLP-1. These endings act as a target for natural GLP-1 (an internal hormone incretin that stimulates glucose-dependent insulin secretion inside the β-cells of the pancreas).

Indications Victoza

It is used in type 2 diabetes mellitus in combination with physical therapy and diet to achieve glycemic control. It can be prescribed as monotherapy; also in combination with one or more oral antidiabetic drugs (sulfonylurea derivatives, as well as metformin or thiazolidinedilones) in people who have not responded to previous treatment. It is also used in combination with insulin in people who have failed to achieve results using liraglutides with metformin.

It is used to reduce the likelihood of developing cardiovascular disorders (such as death due to cardiovascular disease, stroke and myocardial infarction that do not result in death) in diabetics (type 2) with diagnosed cardiovascular pathology – as an addition to standard therapy for cardiovascular diseases (based on an analysis of the period of development of the first significant cardiovascular dysfunction).

Release form

The drug is released in the form of a liquid for subcutaneous injections, inside cartridges with a volume of 3 ml; also inside the pack there are special syringe pens.

Pharmacodynamics

The long plasma half-life is due to 3 mechanisms: self-association, which slows drug absorption, synthesis with albumin, and an increased enzymatic stability index for DPP-4 and NEP enzymes.

Liraglutide interacts with the GLP-1 endings, which increases cAMP values. As a result, glucose-dependent stimulation of insulin secretion develops and the activity of pancreatic β-cells improves. At the same time, under the influence of Victoza, glucose-dependent inhibition of excess glucagon secretion develops. As a result, with an increase in blood sugar levels, inhibition of glucagon secretion develops and insulin secretion is stimulated. At the same time, at low blood glucose values, liraglutide reduces insulin secretion, but does not inhibit glucagon secretion. [ 1 ]

When glycemia is weakened, there is some delay in gastric emptying. The drug reduces weight and fat levels, reducing energy expenditure and the feeling of hunger.

GLP-1 helps physiologically regulate calorie intake and appetite, and its endings are found in several areas of the brain that help regulate appetite.

Pharmacokinetics

Liraglutide is absorbed at a low rate after subcutaneous injection, with a plasma Tmax of 8-12 hours. Plasma Cmax values after subcutaneous administration of a single 600 mcg dose are 9.4 nmol/l.

After administration of a 1.8 mg dose of liraglutide, the mean values of its plasma Css are approximately 34 nmol/l. The level of exposure to the substance increases proportionally to the dose used. After administration of a 1-fold dose of the drug, the intrapopulation variation rate of AUC is 11%. The absolute bioavailability values of the component with a subcutaneous injection are approximately 55%.

The apparent tissue Vd values of the drug after subcutaneous injection are 11-17 L. The average Vd values after intravenous administration are 0.07 L/kg. Most of liraglutide is synthesized with blood protein (>98%).

Following administration of a single dose of [3H]-liraglutide (pre-labeled with a radioactive isotope) to volunteers, unchanged liraglutide was the major constituent of plasma for 24 hours. Two metabolic constituents were detected within plasma (≤9% and ≤5% of total intraplasma radioactivity). Liraglutide is metabolized endogenously (similar to large proteins).

Following single-dose [3H]-liraglutide injection, no unchanged element was recovered in the faeces or urine. Only a small portion of the radioactive components in the form of liraglutide-synthesized metabolic elements (6% and 5%, respectively) was excreted via the kidneys or intestines. Excretion via these routes occurs primarily during the first 6-8 days after administration of the drug. The mean clearance rate following subcutaneous injection of a single dose of the drug is approximately 1.2 L/hour; the half-life is approximately 13 hours.

The exposure to liraglutide in subjects with mild to moderate hepatic impairment is reduced by 13-23%. In subjects with severe impairment, these values are significantly lower (by 44%).

In case of renal failure, exposure is reduced by 33% (CC within 50-80 ml per minute), 14% (CC is 30-50 ml/minute), 27% (CC <30 ml/minute) and 28% (terminal phase of the disease; persons on dialysis).

Dosing and administration

The medicine should be administered subcutaneously, once a day, into the thigh, abdomen or shoulder. It is prohibited to use intramuscular or intravenous administration.

The initial dose is 0.6 mg per day. After using for at least 1 week, the dosage is increased to 1.2 mg. In order to achieve maximum glycemic control, taking into account the clinical effect of the drug, it is permissible to increase the dose to 1.8 mg (also after at least 1 week of using a dose of 1.2 mg). It is prohibited to administer a daily dose greater than 1.8 mg.

When used in addition to metformin or in combination therapy with thiazolidinedione and metformin, the indicated drugs are used in the previous dosages.

The use of Victoza together with sulfonylurea derivatives requires a reduction in the dose of the latter in order to reduce the likelihood of developing side effects of hypoglycemia.

• Application for children

The drug is prohibited for use in pediatrics (in persons under 18 years of age).

Use Victoza during pregnancy

Victoza should not be prescribed during breastfeeding or pregnancy.

Contraindications

Main contraindications:

• diabetes mellitus type 1;
• severe renal dysfunction;
• diabetic ketoacidosis;
• liver dysfunction;
• cardiac insufficiency grade 3-4;
• inflammation in the intestinal area;
• gastric paresis;
• severe intolerance to liraglutide.

Side effects Victoza

Side effects include:

• problems with metabolic processes: hypoglycemia is often observed (especially when combined with sulfonylurea derivatives), loss of appetite and anorexia;
• disorders of the nervous system: headaches often appear;
• digestive disorders: mainly diarrhea and nausea occur. Dyspepsia, constipation, vomiting, gastritis, bloating, belching, pain in the upper abdominal region and GERD often develop;
• Infectious lesions: mainly upper respiratory tract infections are observed;
• signs of allergy: Quincke's edema occurs occasionally;
• Others: manifestations in the thyroid gland are occasionally noted. Sometimes antibodies to liraglutide are formed (does not lead to a weakening of the drug's effectiveness).

Interactions with other drugs

Some delay in gastric emptying associated with liraglutide may also affect the absorption of concomitant oral medications. Diarrhoea associated with Victoza may alter the absorption of concomitant oral medications.

When starting liraglutide, patients taking warfarin should have their INR monitored regularly.

Storage conditions

Victoza should be stored in a place out of reach of small children. Temperature indicators are within 2-8˚C. The solution cannot be frozen.

Shelf life

Victoza can be used for a period of 30 months from the date of production of the therapeutic substance. The shelf life after the first use is 1 month.

Analogues

Analogues of the drug are Guarem, Baeta with Novonorm and Invokana.