Semaglutide (Ozempic) as The New Weight Loss Remedy

Introduction

Semaglutide (Ozempic) CAS №910463-68-2 is a synthetic peptide-based compound belonging to the class of glucagon-like peptide-1 (GLP-1) receptor agonists. Structurally, it is a modified analog of human GLP-1 (7–37) incorporating amino acid substitutions and acylation with a C₁₈ fatty diacid chain to prolong its half-life. These structural modifications enhance its resistance to enzymatic degradation and facilitate albumin binding.

Initially developed for glycemic control in patients with type 2 diabetes mellitus, semaglutide (Ozempic) has demonstrated potent appetite-suppressing properties and significant effects on body weight reduction in clinical settings. These findings led to its reclassification and approval for the long-term management of obesity, positioning it as the first GLP-1 receptor agonist to be approved specifically for weight loss in non-diabetic individuals.

Semaglutide (Ozempic) Pharmacological Activity

The Semaglutide’s (Ozempic) pharmacological action is based on its ability to activate GLP-1 receptors in pancreatic, gastrointestinal, and central nervous system tissues. By mimicking endogenous incretin activity, semaglutide (Ozempic) enhances glucose-dependent insulin secretion, inhibits glucagon release, slows gastric emptying, and modulates hypothalamic appetite regulation. These mechanisms contribute to both improved glycemic control and sustained energy intake reduction, making semaglutide (Ozempic) a key molecule in modern anti-obesity pharmacotherapy.

Physical and Chemical Properties of Semaglutide (Ozempic)

Semaglutide (Ozempic) CAS №910463-68-2 is a synthetic GLP-1 analog composed of 31 amino acid residues and a modified side chain. Its molecular formula is C₁₈₇H₂₉₁N₄₅O₅₉, and the molecular weight is approximately 4113.58 g/mol. The peptide backbone is produced via recombinant expression in Saccharomyces cerevisiae, followed by site-specific chemical modifications. Three major structural changes differentiate semaglutide (Ozempic) from endogenous GLP-1:

• 1) Substitution of alanine with α-aminoisobutyric acid (Aib) at position 8, which prevents enzymatic degradation by dipeptidyl peptidase-4 (DPP-4);
• 2) Acylation of the ε-amino group of Lys26 with a hydrophilic spacer and C18 fatty diacid, which enhances albumin binding and significantly prolongs plasma half-life;
• 3) Substitution of Lys34 with Arg to prevent additional undesired acylation and preserve single-site conjugation.

Physically, semaglutide (Ozempic) is a white to off-white hygroscopic powder with limited solubility in aqueous media across pH 2–6. It is soluble in DMSO at ~3 mg/mL (~0.73 mM), and forms stable α-helical structures in buffered aqueous solutions. The compound’s Topological Polar Surface Area (TPSA) is approximately 1650 Ų, reflecting a highly polar, hydrophilic profile typical of large peptides.

Semaglutide’s (Ozempic) pharmacokinetic profile is heavily influenced by its fatty acid chain, which promotes reversible binding to serum albumin, thereby extending its half-life to 165–184 hours. This albumin binding not only reduces renal clearance but also minimizes enzymatic hydrolysis in plasma.

Lyophilized powder of semaglutide (Ozempic) is very hygroscopic and should be stored in tightly closed light-resistant containers, preferably under an inert atmosphere. The recommended long-term storage conditions are -20 °C ± 5 °C. Protection from oxygen and moisture are necessary to prevent oxidation of aromatic residues and hydrolysis of susceptible amide bonds.

Ozempic is a game-changer. Here’s how it works.

Synthesis of Semaglutide (Ozempic)

The synthesis of semaglutide (Ozempic) CAS №910463-68-2 is a multi-step process involving recombinant peptide production in microbial systems, followed by site-specific chemical modification to introduce structural features that enhance stability. This semi-synthetic approach combines large-scale biosynthesis of the peptide backbone with targeted organic reactions.

1. Recombinant expression

The unmodified semaglutide (Ozempic) peptide backbone is produced by fermentation of genetically modified Saccharomyces cerevisiae. The yeast strain is transformed with an optimized DNA sequence encoding a 31 amino acid GLP-1 analogue, excluding unnatural residues and the fatty acid moiety. During fermentation, the host expresses the peptide either as a fusion protein or in a secreted form, followed by cell lysis or separation of the supernatant to isolate the peptide.

Typically, the peptide is expressed with cleavable tags to facilitate purification. Subsequent processing includes filtration, chromatography, and desalting to obtain pure intermediate peptide. At this stage, the peptide contains only natural amino acids and has no chemical modifications at positions 8, 26, and 34.

2. Site-specific chemical modification

After purification of the native peptide, chemical synthesis is used to introduce key modifications that differentiate semaglutide (Ozempic) from native GLP-1. These modifications are performed in solution phase under controlled conditions and include:

Substitution at position 8: the alanine residue is replaced with α-aminoisobutyric acid (Aib) to block degradation by dipeptidyl peptidase-4 (DPP-4). This unnatural amino acid is typically incorporated via solid-phase peptide synthesis (SPPS) during fragment assembly or ligation.

Selective acylation at Lys26: The ε-amino group of lysine at position 26 is coupled to a hydrophilic linker (e.g., a γ-glutamic acid derivative), which in turn is conjugated to a C18 fatty diacid (octadecanedioic acid). This step is achieved using activated esters (e.g., NHS esters) under mild basic conditions (pH 8–9), which ensures regioselectivity.

Replacement of Lys34 with Arg: To avoid multiple conjugation sites, Lys34 is replaced with arginine, a natural residue that retains a charge without nucleophilicity.

Chemical Reactions of Semaglutide (Ozempic)

Semaglutide (Ozempic) CAS №910463-68-2 is a chemically modified large polypeptide that rarely undergoes small molecule-type organic transformations, but it does undergo predictable biochemical and chemical degradation pathways, including hydrolysis, oxidation, and enzymatic cleavage.

1. Peptide bond hydrolysis

Unmodified peptides are susceptible to non-specific hydrolysis of amide bonds under acidic or basic conditions. Under laboratory conditions, semaglutide (Ozempic) exhibits hydrolytic cleavage at the Gln–Gly and Asn–Ser motifs, which are known spots in peptide degradation.

2. Oxidation reactions

Semaglutide (Ozempic) contains several residues prone to oxidative degradation, in particular tyrosine and histidine:

Tyrosine (Tyr) can undergo electrophilic aromatic substitution reactions with reactive oxygen species (ROS), leading to cross-linking of dityrosine or formation of quinoid structures.

Histidine (His) can be oxidized in the imidazole ring, especially under oxidative stress (e.g., prolonged storage or exposure to peroxides in excipients).

When semaglutide (Ozempic) is incubated at pH 7.4 with 0.1% hydrogen peroxide at 37 °C for 24 hours, oxidative degradation is observed at residue Tyr20.

Semaglutide (Ozempic) degradation is primarily biochemical, occurring via slow enzymatic proteolysis and β-oxidation.

Applications of Semaglutide (Ozempic)

Semaglutide (Ozempic) CAS №910463-68-2 is a long-acting GLP-1 receptor agonist, originally developed as an antidiabetic agent. Semaglutide is approved for chronic weight management with emerging potential in cardiovascular, hepatic, and neurological indications.

1. Treatment of Type 2 Diabetes Mellitus

Semaglutide is clinically approved for the treatment of type 2 diabetes mellitus (T2DM) under the brand names Ozempic (injectable) and Rybelsus (oral). By activating GLP-1 receptors, semaglutide enhances glucose-dependent insulin secretion, suppresses glucagon release, and slows gastric emptying. These effects result in lower fasting and postprandial blood glucose levels without causing significant hypoglycemia.

2. Obesity and Chronic Weight Management

Under the brand name Wegovy, semaglutide is approved for long-term weight loss in adults. The mechanism involves hypothalamic appetite suppression, delayed gastric emptying, and decreased energy intake, independent of glycemic control. Clinical studies have shown an average decrease in body weight of up to 15%.

3. Cardiovascular and Liver Benefits of Semaglutide (Ozempic)

In addition to glycemic and weight-related outcomes, semaglutide has demonstrated cardioprotective effects. Semaglutide significantly reduced the risk of major adverse cardiovascular events by 26% in patients with high-risk T2DM. Proposed mechanisms include improved endothelial function, anti-inflammatory activity, and modulation of the lipid profile. Additionally, semaglutide is being investigated for the treatment of non-alcoholic steatohepatitis due to its beneficial effects on liver fat accumulation, liver enzymes, and fibrosis markers.

4. New and Investigational Indications

Semaglutide’s central action via GLP-1 receptors has attracted interest in neurodegenerative disease research, including potential use in Alzheimer’s disease and Parkinson’s disease, where GLP-1 analogues may have neuroprotective and anti-inflammatory effects. The compound is also being explored for use in metabolic syndrome and addiction medicine, where the circuits of appetite and reward intersect.

Health Effects of Semaglutide (Ozempic)

The therapeutic effects of semaglutide (Ozempic) CAS №910463-68-2 have been studied in the context of diabetes and obesity, with health effects of the compound being both beneficial and unfavorable.

Pharmacodynamic Health Benefits

Activation of GLP-1 receptors by semaglutide (Ozempic) results in several clinically desirable outcomes. These include enhancing glucose-dependent insulin secretion, suppressing inappropriate glucagon release, delaying gastric emptying, and suppressing appetite via central hypothalamic pathways. Clinical trials have also demonstrated secondary benefits such as lower systolic blood pressure, improved lipid profiles, and reduced inflammatory markers.

Adverse and Dose-Dependent Effects

Despite its therapeutic benefits, semaglutide (Ozempic) is associated with a number of adverse effects, most of which are dose-related. The most commonly reported events include nausea, vomiting, constipation and diarrhea, especially during the dose escalation phase. These effects are attributed to the compound’s effects on gastrointestinal motility and central vomiting pathways. Rare but clinically significant adverse events include acute pancreatitis, gallbladder disease.

Systemic Considerations and Long-Term Safety

Long-term administration of semaglutide (Ozempic) has not been associated with significant organ toxicity, genotoxicity or carcinogenicity in non-clinical models, with the exception of thyroid type-specific findings. Semaglutide (Ozempic) is not recommended during pregnancy or lactation, and its safety in children remains under investigation.

Conclusion

Semaglutide (Ozempic) CAS №910463-68-2 is an example of structurally optimized peptide drugs in the treatment of complex multifactorial diseases. Chemically, semaglutide demonstrates how small but targeted molecular changes can yield major therapeutic benefits—especially in prolonging half-life, metabolic stability, and receptor specificity. These features not only enhance clinical efficacy, but also provide formulation flexibility and economic scalability in industrial production.

Bibliography

1. Smits M. M., Van Raalte D. H. Safety of semaglutide //Frontiers in endocrinology. – 2021. – Т. 12. – С. 645563. https://doi.org/10.3389/fendo.2021.645563
2. Bergmann N. C. et al. Semaglutide for the treatment of overweight and obesity: a review //Diabetes, Obesity and Metabolism. – 2023. – Т. 25. – №. 1. – С. 18-35. https://doi.org/10.1111/dom.14863
3. Knudsen L. B., Lau J. The discovery and development of liraglutide and semaglutide //Frontiers in endocrinology. – 2019. – Т. 10. – С. 155. https://doi.org/10.3389/fendo.2019.00155
4. Yang X. D., Yang Y. Y. Clinical pharmacokinetics of semaglutide: a systematic review //Drug Design, Development and Therapy. – 2024. – С. 2555-2570. https://doi.org/10.2147/DDDT.S470826