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    Semaglutide

    5MG

    $40
    In Stock

    This product is for research purposes only. Not for human consumption.

    Purity: >98% (HPLC verified)

    Formulation: Lyophilized powder

    Molecular Formula: C187H291N45O59

    Molecular Weight: 4113.64 g/mol

    CAS Number: 910463-68-2

    PubChem CID: 56843331

    Semaglutide Molecular Structure

    Semaglutide

    GLP-1 Agonists

    Overview

    Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that represents a breakthrough in metabolic medicine. As a synthetic peptide analog of human GLP-1, it mimics the action of this naturally occurring incretin hormone but with significantly enhanced stability and duration of action.

    Originally developed for type 2 diabetes management, semaglutide has demonstrated remarkable efficacy across multiple therapeutic areas including weight management, cardiovascular protection, and metabolic health optimization.

    The molecule features strategic modifications including an acylation side chain that enables albumin binding, resulting in a prolonged half-life of approximately one week, making it suitable for once-weekly administration. This pharmacokinetic profile has revolutionized treatment paradigms by improving patient compliance while maintaining consistent therapeutic effects.

    Mechanism of Action

    Semaglutide exerts its multifaceted effects through several interconnected pathways. Upon administration, it binds to and activates GLP-1 receptors distributed throughout the body, including pancreatic beta cells, the gastrointestinal tract, and specific regions of the central nervous system.

    Pancreatic Effects

    In pancreatic beta cells, GLP-1 receptor activation triggers glucose-dependent insulin secretion, meaning insulin release is enhanced only when blood glucose levels are elevated, thereby minimizing hypoglycemia risk. Simultaneously, semaglutide suppresses inappropriate glucagon secretion from pancreatic alpha cells, further contributing to improved glycemic control.

    Gastrointestinal Effects

    The peptide significantly delays gastric emptying through actions on the gastric smooth muscle and vagal afferents, which slows nutrient absorption and helps regulate postprandial glucose excursions.

    Central Nervous System Effects

    Perhaps most notably for weight management applications, semaglutide crosses the blood-brain barrier to act on GLP-1 receptors in the hypothalamus and brainstem, specifically targeting the arcuate nucleus and nucleus tractus solitarius. These central actions reduce appetite, enhance satiety, and decrease food cravings through modulation of pro-opiomelanocortin (POMC) neurons and other appetite-regulating pathways.

    Cardiovascular Effects

    Additionally, semaglutide has demonstrated cardioprotective effects independent of glucose lowering, possibly through anti-inflammatory mechanisms, improved endothelial function, and favorable effects on blood pressure and lipid metabolism.

    Research Findings

    The clinical research portfolio for semaglutide is exceptionally comprehensive, spanning multiple large-scale, international, randomized controlled trials.

    STEP Clinical Trial Program

    The landmark STEP (Semaglutide Treatment Effect in People with obesity) clinical trial program represents the most extensive investigation of semaglutide for weight management:

  1. STEP 1 (New England Journal of Medicine): Enrolled 1,961 adults with obesity or overweight and demonstrated a mean weight loss of 14.9% from baseline at 68 weeks with semaglutide 2.4 mg compared to 2.4% with placebo. Notably, 86.4% of participants achieved at least 5% weight loss, and 69.1% achieved at least 10% weight loss.

  2. STEP 2: Specifically examined adults with type 2 diabetes and obesity, showing mean weight reduction of 9.6% with semaglutide 2.4 mg versus 3.4% with placebo, alongside significant improvements in HbA1c levels.

  3. STEP 3: Combined semaglutide with intensive behavioral therapy, achieving mean weight loss of 16.0%.

  4. STEP 4: Assessed weight maintenance after initial weight loss, demonstrating that continued semaglutide treatment resulted in additional weight reduction whereas placebo led to weight regain.

    SUSTAIN Clinical Trial Series

    Beyond the STEP program, the SUSTAIN clinical trial series established semaglutide's efficacy for type 2 diabetes management. SUSTAIN 6, a cardiovascular outcomes trial, revealed a 26% reduction in major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. This cardiovascular benefit was observed across diverse patient populations and appears to extend beyond glucose control effects.

    SELECT Trial

    The SELECT trial, one of the largest cardiovascular outcomes trials in obesity medicine, enrolled over 17,000 participants with established cardiovascular disease and obesity or overweight (without diabetes) and demonstrated a 20% reduction in MACE with semaglutide 2.4 mg.

    Additional Research Areas

    Emerging research has also investigated semaglutide's potential benefits in:

  5. Liver Disease: Non-alcoholic fatty liver disease (NAFLD/NASH) studies showing significant reductions in liver fat content and improvements in inflammatory markers.

  6. Metabolic Health: Favorable effects on lipid profiles, with reductions in triglycerides and LDL cholesterol, alongside improvements in markers of systemic inflammation.

  7. Neuroprotection: Promising results in animal models of neurodegenerative diseases, with ongoing clinical trials examining potential applications in Alzheimer's disease and Parkinson's disease.

  8. Quality of Life: Sustained improvements in obesity-related comorbidities including obstructive sleep apnea, osteoarthritis symptoms, and overall quality of life measures.

    9. Research Applications

    • Type 2 diabetes management and glycemic control research
    • Obesity treatment and long-term weight management studies
    • Cardiovascular disease prevention and outcomes research
    • Metabolic syndrome and insulin resistance studies
    • Appetite regulation and satiety mechanism research
    • Non-alcoholic fatty liver disease (NAFLD/NASH) investigations
    • Cardiovascular risk reduction in obesity research
    • Inflammation and oxidative stress studies
    • Neuroprotection and cognitive function research
    • Quality of life and obesity-related comorbidity studies
    • Polycystic ovary syndrome (PCOS) research
    • Bariatric surgery alternative studies

    Safety Profile

    Semaglutide has been extensively evaluated for safety across more than 10,000 participants in clinical trials, with exposure durations extending beyond 3 years in some studies. The safety profile is well-characterized and generally favorable when used according to prescribing guidelines.

    Common Side Effects

    The most commonly reported adverse events are gastrointestinal in nature:

    • Nausea (approximately 20-44% of participants)
    • Diarrhea (approximately 30%)
    • Vomiting (approximately 24%)
  9. Constipation (approximately 24%)

    These symptoms are typically mild to moderate in severity, tend to occur most frequently during dose escalation, and generally diminish over time as tolerance develops. Following a gradual dose titration schedule significantly reduces the incidence and severity of gastrointestinal side effects.

    Serious Adverse Events

    Serious adverse events are uncommon but have been documented and warrant appropriate monitoring:

  10. Pancreatitis: Cases of acute pancreatitis have been reported (approximately 0.2-0.3% incidence). Patients should discontinue semaglutide and seek immediate medical attention if they experience severe, persistent abdominal pain.

  11. Gallbladder Events: Cholelithiasis and cholecystitis have been observed at slightly higher rates, likely related to rapid weight loss rather than a direct drug effect.

  12. Thyroid Considerations: In preclinical rodent studies, semaglutide was associated with thyroid C-cell tumors; however, this has not been observed in human trials. Semaglutide is contraindicated in individuals with a personal or family history of medullary thyroid carcinoma or MEN 2.

    Additional Safety Information

    Hypoglycemia risk is minimal with semaglutide monotherapy due to its glucose-dependent mechanism of action, though risk increases when combined with insulin or sulfonylureas. Cardiovascular safety has been thoroughly evaluated, with trials demonstrating not only safety but also significant cardiovascular benefits. Renal safety data indicate that semaglutide is generally well-tolerated in patients with mild to moderate renal impairment.

    Overall, when prescribed appropriately with proper patient selection, dose titration, and monitoring, semaglutide presents a favorable benefit-risk profile for its approved indications.

    13. Scientific References

    1. Wilding, J. P., et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 384(11), 989-1002.
    2. Davies, M., et al. (2021). Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. The Lancet, 397(10278), 971-984.
    3. Wadden, T. A., et al. (2021). Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA, 325(14), 1403-1413.
    4. Rubino, D., et al. (2021). Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA, 325(14), 1414-1425.
    5. Marso, S. P., et al. (2016). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine, 375(19), 1834-1844.
    6. Lincoff, A. M., et al. (2023). Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine, 389(24), 2221-2232.
    7. Newsome, P. N., et al. (2021). A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. New England Journal of Medicine, 384(12), 1113-1124.
    8. Garvey, W. T., et al. (2022). Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature Medicine, 28(10), 2083-2091.

    Research Use Only

    This product is intended for research purposes only and is not for human consumption, therapeutic use, or diagnostic applications. Please ensure compliance with all applicable regulations and institutional guidelines.