The half-life (T1/2) of semaglutide is approximately 1 week. Tmax in plasma was reached between 1 to 3 days after administration of the drug dose. The AUC was achieved after 4-5 weeks of once-weekly dosing. After subcutaneous administration of semaglutide in doses of 0.5 mg and 1 mg, the mean steady-state concentrations in patients with type 2 diabetes were approximately 16 nmol/L and 30 nmol/L, respectively. Exposure to semaglutide doses of 0.5 mg and 1 mg increases proportionally with the administered dose. Similar exposure is achieved when semaglutide is administered subcutaneously in the abdomen, thigh, or arm. The absolute bioavailability of semaglutide after subcutaneous administration was 89%. The average volume of distribution of semaglutide in tissues after subcutaneous administration to patients with type 2 diabetes was approximately 12.5 L. Semaglutide is highly bound to plasma albumin (>99%). Semaglutide is metabolized by proteolytic cleavage of the peptide backbone of the protein and subsequent beta-oxidation of the fatty acid side chain. The gastrointestinal tract and kidneys are the main routes of elimination of semaglutide and its metabolites. Two-thirds of the administered dose of semaglutide is excreted by the kidneys, and one-third is excreted through the intestines. Approximately 3% of the administered dose is excreted by the kidneys as unchanged semaglutide. In patients with type 2 diabetes, the clearance of semaglutide was approximately 0.05 L/h. With an elimination half-life of approximately 1 week, semaglutide will be present in the systemic circulation for approximately 5 weeks after the last dose of the drug is administered.

Type 2 diabetes in the context of diet and physical exercise to improve glycemic control as:

• Monotherapy;
• Combination therapy with other oral hypoglycemic agents (OHAs) such as metformin, metformin and a sulfonylurea derivative, metformin and/or a thiazolidinedione, in patients who have not achieved adequate glycemic control with previous therapy;
• Combination therapy with insulin in patients who have not achieved adequate glycemic control with treatment with this drug and metformin.

The method of application and dosage regimen of a specific drug depend on its dosage form and other factors. The optimal dosage regimen is determined by the doctor. It is essential to strictly adhere to the correspondence of the specific drug's dosage form to the indications for use and dosage regimen. Subcutaneously into the abdomen, thigh, or shoulder. Administered once a week at any time, regardless of food intake. If necessary, the day of weekly administration can be changed provided that the interval between two injections is at least 3 days (> 72 hours). The initial dose is 0.25 mg once a week. After 4 weeks of use, the dose should be increased to 0.5 mg once a week.

From the immune system: rarely - anaphylactic reactions. From metabolism and nutrition: very common - hypoglycemia when used concurrently with insulin or a sulfonylurea derivative; common - hypoglycemia when used concurrently with other OHAs, decreased appetite. From the nervous system: common - dizziness, infrequently - dysgeusia. From the organs of vision: common - complications of diabetic retinopathy. From the cardiovascular system: increased heart rate. From the gastrointestinal tract: very common - nausea, diarrhea; common - vomiting, abdominal pain, bloating, constipation, dyspepsia, gastritis, gastroesophageal reflux disease, belching, flatulence. From the liver and biliary tract: common - cholelithiasis. Local reactions: reactions at the injection site. Systemic reactions: fatigue. Laboratory and instrumental data: common - increased lipase activity, increased amylase activity, weight loss.

Use is contraindicated in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. The drug does not replace insulin.

The use of GLP-1R agonists may be associated with gastrointestinal adverse reactions. This should be considered when treating patients with renal insufficiency, as nausea, vomiting, and diarrhea may lead to dehydration and worsening kidney function.

Cases of acute pancreatitis have been reported with the use of GLP-1R agonists. Patients should be informed about the characteristic symptoms of acute pancreatitis. Caution should be exercised in patients with a history of pancreatitis.

Patients receiving the drug in combination with a sulfonylurea derivative or insulin may have an increased risk of hypoglycemia.

Caution should be exercised when using semaglutide in patients with diabetic retinopathy receiving insulin therapy. Such patients should be under constant supervision and receive treatment according to clinical recommendations.

In the post-registration period of use of another GLP-1 analog, liraglutide, cases of medullary thyroid cancer (MTC) have been noted. There is insufficient data to establish or exclude a causal relationship between the development of MTC and the use of GLP-1 analogs. Patients should be informed of the risk of MTC and the symptoms of thyroid tumor (appearance of a lump in the neck, dysphagia, shortness of breath, persistent hoarseness). A significant increase in plasma calcitonin concentration may indicate MTC (in patients with MTC, plasma calcitonin concentrations are usually >50 ng/L). If an increase in plasma calcitonin concentration is detected, further examination of the patient is necessary. Patients with thyroid nodules detected during a medical examination or thyroid ultrasound should also undergo additional examination. The use of semaglutide in patients with a personal or family history of MTC or with type 2 MEN syndrome is contraindicated.

The drug has no or minor effect on the ability to drive vehicles or operate machinery. Patients should be warned that they should take precautions to avoid hypoglycemia while driving vehicles and operating machinery, especially when combined with a sulfonylurea derivative or insulin.

Drug Interactions Delayed gastric emptying with semaglutide use may affect the absorption of concomitant oral medications. Semaglutide should be used with caution in patients receiving oral medications requiring rapid absorption in the gastrointestinal tract.

Substances added to the drug may cause degradation of semaglutide. It is not allowed to mix with other drugs, including infusion solutions.