Suzhou Pharmaserve Technology Co., Ltd.

Semaglutide is a lipopeptide with a linear sequence of 31 amino acids. Like human Glucagon-like peptide-1 (GLP-1), it is used in combination with diet and exercise in the therapy of type 2 diabetes mellitus. It works as an anti-obesity agent, a neuroprotective agent, and an appetite depressant. Semaglutide can be commercialized as a synthetic generic product after approval of an abbreviated new drug application (ANDA) or comparable applications with other regulatory authorities. The length and modifications make technical excellence and regulatory expertise a prerequisite for efficient filing and fast approval. High material quality and yield, robust processes including secure supply and innovative approaches at high-tech facilities will enable our customers to achieve their business goals.

Semaglutide Pharmaserve is indicated to improve glycemic control in adults with type 2 diabetes mellitus as an adjunct of diet and exercise. The approved therapeutic doses are 0.5 mg and 1 mg.7 Diabetes mellitus type 2 is a long-term metabolic disorder characterized by high blood sugar, insulin resistance and lack of insulin. Its onset is determined by the loss ability of beta cells to respond to an increased plasma glucose. This disease is predominantly caused by lifestyle factors like overweight and obesity. The key feature on type 2 diabetes is the presence of insulin resistance which reduced the capacity of insulin to exert its functions at normal at any given concentration. The secretion of insulin is stimulated by the action of incretins in the gut like glucagon-like peptide 1, which also delays gastric emptying and induces satiety, and glucose-dependent insulinotropic polypeptide.

Drugs like Semaglutide Pharmaserve affect the glucose control through several different mechanisms like the increase of insulin secretion, slow of gastric emptying, and reduction of postprandial glucagon and food intake. The glucose homeostasis depends on hormones like insulin and amylin secreted in pancreatic beta cells, glucagon secreted in pancreatic alpha cells and gastrointestinal peptides like glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide. When glucose is administered orally, GLP-1 will stimulate the synthesis of insulin by stimulating pancreatic islets, it will also slow the gastric emptying, inhibit post-meal glucagon release and reduce food intake. GLP-1 has a major role in glucose management and Semaglutide presents an analog structure which allows it to perform all the activities of GLP-1.3 The innovative section of Semaglutide is the presence of structural modifications (amino acid substitution at position 8) that generate superior stability against dipeptidyl peptidase-4 which is an enzyme that degrades incretins like GLP-1. The structure of Semaglutide (lysine acylation with a spacer and C-18 fatty di-acid at position 26) also permits an increased and specific binding to plasma albumin; as well as a modification (amino acid substitution at position 34) that prevents C-18 fatty di-acid binding in wrong sites. All these characteristics donate Semaglutide with an extended half-life, increasing patient compliance and quality of life.

In clinical trials, Semaglutide Pharmaserve reduced significantly the glycated hemoglobin (HbA1c) compared to other medications like sitagliptin, exenatide and insulin glargine U100. The HbA1c protein is a standard measure of high glucose as in normal conditions the hemoglobin forms 1-deoxyfructose. In the trials, it was also showed the ability of Semaglutide to reduce the body weight. After 12 weeks of treatment, Semaglutide lowered fasting and postprandial glucose concentrations by increasing insulin production and decreasing glucagon secretion. It also lowered fasting triglycerides and VLDL cholesterol.

The metabolism of Semaglutide Pharmaserve is slowly but extensively metabolized prior to excretion. This was observed as 83% of the administered dose found in the plasma is composed of the unchanged drug. As a product of the metabolism, six different metabolites were identified in human plasma in which the major metabolite, named P3, accounted for 7.7% of the administered dose, thus indicating a component below the relative exposure limit in the safety assessment. The metabolites were formed following proteolytic cleavage of the peptide backbone and beta-oxidation of the fatty acid side chain. The known enzymes to be involved in the degradation of Semaglutide are dipeptidyl peptidase (DPP-4) and neural endopeptidase (NEP). DPP-4 inactivates semaglutide truncating the N-terminal sequence and NEP hydrolyze peptide bonds.

In preclinical toxicity studies with Semaglutide Pharmaserve, there was observed the presence of mild c-cell hyperplasia, nests and dilated ultimobranchial ducts after three months of exposure with a 17X of the clinical dose. There was also reports of liver necrosis and centrilobular hypertrophy mainly in man in the same doses. Some ECG abnormalities and multifocal vacuolation and degeneration were observed in high dose studies (27X)