Semaglutide (3mg / 5mg / 10mg)

Description

 

Semaglutide Peptide

Overview
Semaglutide is a synthetic glucagon-like peptide-1 receptor agonist (GLP-1 RA) originally developed for the management of type 2 diabetes mellitus and obesity-related metabolic dysfunction. Structurally, it is a modified analog of the naturally occurring human GLP-1 hormone, designed to resist enzymatic degradation by dipeptidyl peptidase-4 (DPP-4), thereby offering a prolonged half-life and enhanced therapeutic efficacy.

Semaglutide acts by mimicking the effects of endogenous GLP-1 — a hormone released in response to food intake that promotes insulin secretion, suppresses glucagon release, delays gastric emptying, and enhances satiety. These combined actions contribute to improved glycemic control, weight reduction, and metabolic regulation.

Semaglutide’s modifications — specifically substitution at position 8 with Aib (α-aminoisobutyric acid) and attachment of a C18 fatty diacid chain via a glutamic acid spacer — enhance its binding affinity to albumin and prolong its half-life to approximately one week, making it suitable for once-weekly dosing.

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Mechanism of Action

Semaglutide functions primarily as a GLP-1 receptor agonist and exerts its actions through the following mechanisms:

1. Enhanced Insulin Secretion:
   It stimulates insulin release from pancreatic β-cells in a glucose-dependent manner, promoting glucose uptake into tissues and reducing blood sugar levels without causing hypoglycemia under normal conditions.

2. Glucagon Suppression:
   It inhibits glucagon secretion from pancreatic α-cells, which helps reduce hepatic glucose production.

3. Delayed Gastric Emptying:
   By slowing the rate at which food leaves the stomach, Semaglutide contributes to prolonged satiety and reduced appetite, aiding in calorie control and weight management.

4. Central Appetite Regulation:
   Semaglutide acts on GLP-1 receptors in the hypothalamus, influencing the brain’s appetite-regulating centers and leading to a decreased desire for food intake.

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Pharmacokinetics

• Molecular Formula: C₁₈₇H₂₉₁N₄₅O₅₉

• Molecular Weight: 4113.58 g/mol

• Form: Lyophilized powder

• Purity: >99% (HPLC validated)

• CAS Number: 910463-68-2

• Administration Route: Subcutaneous injection

• Half-life: Approximately 168 hours (7 days)

• Bioavailability: ~89% (subcutaneous)

Semaglutide’s long half-life allows for once-weekly administration, improving adherence compared to daily GLP-1 analogs.

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Research Applications

While Semaglutide is clinically approved under trade names such as Ozempic®, Wegovy®, and Rybelsus® for specific therapeutic uses, in research contexts, it is being studied for a wide range of potential applications, including:

1. Weight Management and Obesity Research:
   Semaglutide has demonstrated consistent and significant reductions in body weight across multiple trials, with average total body weight (TBW) reductions of 10–15% at higher doses (2.4 mg weekly). Research suggests that this weight loss is due to decreased caloric intake rather than increased energy expenditure.

2. Cardiometabolic Health:
   Ongoing studies investigate Semaglutide’s potential in reducing cardiovascular risk factors, improving lipid metabolism, and lowering blood pressure. Clinical data suggest it may reduce major adverse cardiovascular events (MACE) in diabetic populations.

3. Nonalcoholic Steatohepatitis (NASH):
   Preclinical data and Phase 2 studies indicate that Semaglutide may reduce hepatic steatosis and inflammatory markers, making it a promising candidate in NASH and fatty liver disease research.

4. Addiction and Neurobehavioral Studies:
   Emerging studies are exploring Semaglutide’s potential impact on reward pathways, appetite suppression, and dopaminergic signaling, which could have implications for addiction and compulsive behavior research.

Storage and Stability

• Store at -20°C or below.

• Protect from light and moisture.

• Reconstituted solutions should be used promptly or stored refrigerated (2–8°C) for up to 48 hours.

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References

1. Wilding JPH et al., N Engl J Med. 2021;384(11):989–1002. [STEP 1 Trial]

2. Marso SP et al., N Engl J Med. 2016;375(19):1834–1844. [SUSTAIN-6]

3. Davies MJ et al., Lancet Diabetes Endocrinol. 2017;5(5):341–354. [PIONEER 3]

 

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Clinical Data and Efficacy

Key Trials:

• STEP 1–4: Demonstrated superior weight loss and glycemic control vs placebo.

• SUSTAIN 6: Demonstrated a 26% reduction in major cardiovascular events.

• PIONEER: Evaluated oral Semaglutide (Rybelsus®) for glucose control.

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Safety and Tolerability

Commonly reported side effects in both animal and human studies include:

• Nausea (up to 30%)

• Vomiting (10–15%)

• Diarrhea (15–20%)

• Constipation (10–12%)

• Injection site reactions (2–5%)

Serious Adverse Events (rare):

• Pancreatitis

• Gallbladder disease

• Potential thyroid C-cell tumors (observed in rodents, not yet confirmed in humans)

Contraindications (Research Use Caution):

• History of medullary thyroid carcinoma (MTC)

• Multiple endocrine neoplasia syndrome type 2 (MEN2)

• Severe gastrointestinal disorders