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Semaglutide is a synthetic peptide analog of the incretin hormone glucagon-like peptide 1 (GLP-1). It has been found safe and effective for use in type 2 diabetes, reducing cardiovascular risk in diabetics, and as a weight management agent in both adults and adolescents. Researchers are currently investigating whether a high dose version of semaglutide can further help combat the global obesity pandemic.

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    What is Semaglutide?

    Semaglutide belongs to a class of drugs called glucagon-like peptide-1 receptor agonists (GLP-1-RAs). GLP-1-RAs work by mimicking the action of the hormone GLP-1, which helps regulate blood sugar levels by increasing insulin secretion and reducing the production of glucose in the liver [1].

    As a GLP-1-RA, semaglutide targets GLP-1 receptors found in the pancreatic beta cells, liver cells, and brain cells. Researchers have observed a number of beneficial effects upon semaglutide’s activation of the GLP-1 receptor, including increased insulin secretion, glucagon inhibition, slowed gastric emptying, and increased satiety [1].

    How Semaglutide Improves Blood Sugar Control

    Semaglutide increases insulin secretion from pancreatic beta cells in response to elevated blood sugar levels. This enhanced insulin release helps transport glucose from the bloodstream into cells, where it can be utilized for energy or stored for later use. By increasing insulin availability, semaglutide helps lower blood sugar levels, especially after meals [2].

    Some studies suggest that GLP-1-RAs, including semaglutide, may improve the sensitivity of cells to insulin. This means that even at lower insulin levels, the body's cells can respond more effectively to insulin, further aiding in blood sugar regulation [2].

    In addition to enhancing insulin secretion, semaglutide also inhibits the production and release of glucagon—a hormone that works opposite to insulin. Glucagon raises blood sugar levels by promoting the release of stored glucose from the liver. By reducing glucagon levels, semaglutide helps prevent excessive glucose production, contributing to better blood sugar control [1].

    How Semaglutide Causes Weight Loss

    The mechanisms through which semaglutide promotes weight loss may be summed up in three parts [3]:

    • Increased Satiety. Semaglutide acts on the brain's appetite-regulating centers, leading to increased feelings of fullness (satiety) and reduced appetite. This can result in decreased food intake and a reduced desire to eat, which contributes to weight loss.
    • Slowed Gastric Emptying. Semaglutide slows down emptying of the stomach, which can help people feel fuller for longer periods after meals. By delaying the entry of nutrients into the small intestine, semaglutide reduces the rapid spikes in blood sugar levels after eating, helping to control hunger and reduce food consumption.
    • Reduced Caloric Intake. Due to the increased satiety and reduced appetite, semaglutide therapy recipients may naturally consume fewer calories, leading to weight loss over time.
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    Semaglutide Benefits | Clinical Trial Data

    While originally developed for the management of type 2 diabetes, semaglutide has also been found to exhibit additional benefits like weight loss and cardiovascular risk reduction.

    Let’s take a closer look at the known benefits of semaglutide.

    Semaglutide as a Diabetes Treatment

    Semaglutide is well-studied for its safety and efficacy in type 2 diabetes management. The following clinical development programs shed light on the peptide’s use as an antidiabetic.

    • SUSTAIN Trials


      The SUSTAIN clinical trial program evaluated the safety and efficacy of semaglutide in the treatment of type 2 diabetes. While the program is still ongoing, the trials published to date have involved a variety of dosing regimens and comparisons to other diabetes medications, including insulin glargine as an add-on to metformin. Semaglutide safely and effectively lowered blood sugar levels and promoted weight loss in people with type 2 diabetes [4].

    • PIONEER Trials

      The PIONEER trials investigated the use of oral semaglutide (a tablet form) in the treatment of type 2 diabetes. These trials compared oral semaglutide to other diabetes medications, including sitagliptin and liraglutide (another GLP-1-RA). The results showed that oral semaglutide was effective in reducing blood sugar levels and had potential weight loss benefits. Oral semaglutide is designed to be taken once daily and is generally restricted to diabetic patients [5].

    Semaglutide for Weight Loss

    Several clinical trials have evaluated the effectiveness of semaglutide for weight loss. The most notable series is the STEP (Semaglutide Treatment Effect in People with Obesity) trial program, which involves large-scale phase 3 trials.

    In these trials thus far, semaglutide has been administered via a once-weekly injection to participants with overweight or obesity. The trial volunteers treated with semaglutide achieved significant and sustained weight loss compared to those on placebo. The weight loss observed was typically greater than that achieved with other weight loss medications or lifestyle interventions [6].

    Based on the positive results from clinical trials, the United States Food and Drug Administration (FDA) approved semaglutide for chronic weight management at a higher dose than that used for diabetes, 2.4mg/weekly. The peptide has also been approved for weight reduction in obese adolescents aged 12-17 [6].

    Semaglutide for Cardiovascular Risk Reduction

    Researchers believe that semagltutide’s vast anti-inflammatory and metabolic benefits contribute to its cardioprotective potential. Semaglutide is already approved as a medication for cardiovascular risk reduction in T2D, and is currently being investigated for the same use in non-diabetics.

    In the SUSTAIN 6 trial, conducted on over 3,000 patients with high risk of cardiovascular disease, semaglutide substantially reduced the incidence of cardiovascular events compared with placebo [1, 4].

    Interestingly, a meta-analysis of studies on overweight hypertensive individuals without diabetes reported that semaglutide treatment can lead to a significant reduction in blood pressure. This effect may be partly attributed to the medication's beneficial effects on weight loss and improved insulin sensitivity [7].

    Semaglutide Side Effects and Safety

    Semaglutide may cause side effects in some test subjects. Most of these side effects involve mild to moderate gastrointestinal disturbances, and are common among GLP-1-RAs [8]. Some adverse effects associated with semaglutide are listed below.

    Common Side Effects

    The most commonly reported side effects of semaglutide are [9]:

    • Dyspepsia
    • Dizziness
    • GERD
    • Nausea
    • Diarrhea
    • Abdominal pain
    • Nasopharyngitis
    • Injection-related complications (redness, pain, infection)

    Serious Side Effects

    These rare but considerably more serious side effects have also been reported [9]:

    • Acute kidney injury
    • Diabetic retinopathy complications in patients with type 2 diabetes
    • Acute gallbladder disease
    • Acute pancreatitis

    Safety Considerations

    Because some rodent studies showed a dose- and duration-dependent development of thyroid C-cell tumors and medullary thyroid carcinoma following semaglutide administration, subjects with a family history of these diseases or multiple endocrine neoplasia should be excluded from semaglutide trials [9].

    However, the safety profile of semaglutide in humans is favorable, and there has been no data suggesting that humans are at an increased risk for developing these types of diseases while undergoing semaglutide treatment [10].

    Precautions and Warnings

    Because semaglutide increases insulin production, it should not be administered alongside insulin secretagogues due to the risk of hypoglycemia. Semaglutide should not be used by pregnant women or by children under the age of 12, and is not intended for use in type 1 diabetes [9].

    Overall, research into semaglutide safety reports that it is well-tolerated by most study volunteers. Most side effects will diminish over time and should be minimal if a proper dosing schedule is followed.

    Semaglutide Dosage Calculator and Protocol

    Semaglutide has been FDA-approved for the treatment of both type 2 diabetes and chronic weight management, though each application requires a different dosing protocol.

    Here is a brief overview of subcutaneous dosing guidelines for both indications:

    Semaglutide Dosing for Diabetes

    Semaglutide treatment is an effective way for type 2 diabetics to keep blood sugar within a healthy range.

    Here is how semaglutide is dosed for type 2 diabetes [11]:

    • Semaglutide Schedule for T2D Management:
      - Weeks 1-4: 0.25mg
      - Weeks 5-8: 0.5mg
      - Weeks 9 and beyond: up to 1mg if needed to control blood sugar

    • Frequency: Administer semaglutide subcutaneously once per week.
    • Study Duration: Continuous
    • Notes: Subjects must follow the titration protocol to minimize the occurrence of side effects. Oral semaglutide for T2DM requires daily administration at much higher doses.

    Semaglutide Dosing for Weight Loss

    Semaglutide for weight loss is ultimately administered at a higher maintenance dose than that for type 2 diabetes. The following dose escalation schedule is recommended for this use of semaglutide [11]:

    • Semaglutide Titration for Weight Loss:
      - Weeks 1-4: .25mg
      - Weeks 5-8: .5mg
      - Weeks 9-12: 1mg
      - Weeks 13-15: 1.7mg
      - Week 17 and beyond: 2.4mg

    • Frequency: Administer semaglutide subcutaneously once per week.
    • Study Duration: Continuous
    • Notes: Follow this schedule closely to avoid complications like gastrointestinal distress. Subjects must never skip to a higher dose prematurely, but may stay at a lower dose for longer or indefinitely if a higher dose is not well-tolerated.

    Using bacteriostatic water as a diluent instead of sterile water allows for storing semaglutide in the refrigerator for up to 28 days [12].

    Buying Semaglutide for Research Purposes

    The only FDA-approved products containing semaglutide pertain exclusively to the pharmaceutical company Novo Nordisk. Healthcare providers may prescribe brand names Ozempic, Wegovy, and Rybelsus to qualified patients [9, 13].

    Semaglutide for research purposes is also available online from select peptide vendors. Researchers interested in experimentation with semaglutide may wish to review the risks associated with online purchases of semaglutide:

    • Counterfeit products: Any company can sell a vial of powder and label it as semaglutide. Without a certificate of analysis (COA), the buyer cannot be sure that the vial contains real semaglutide.
    • Unsafe or contaminated products: Again, without a COA, there is no way for a buyer to know that their semaglutide is pure and uncontaminated. When researching semaglutide, the lab will need to be sure that there are no fillers, heavy metals, or other contaminants in the peptide.
    • Legal and regulatory issues: Scientists must adhere to strict regulations and guidelines when conducting semaglutide research studies. Legal issues can arise if there are concerns about compliance with these regulations.

    Additionally, the FDA does not guarantee that any non-prescription form of semaglutide will be safe or effective. They specifically warn against the use of semaglutide sodium and semaglutide acetate, which are salt forms of semaglutide instead of the proven base form [14].

    Where to Buy Semaglutide Online? | 2024 Edition

    Qualified researchers can acquire semaglutide without a prescription for experimental or educational purposes.

    However, caution is required to avoid buying low-grade peptide products that run the risk of hazardous side effects and ineffective research.

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    How to Purchase Semaglutide Online?

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    Bacteriostatic Water For Semaglutide

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    How is semaglutide taken?

    Semaglutide should be administered once weekly subcutaneously, at a dose ranging from 0.5mg to 2.4mg, depending on the dosing schedule, research goal, and test subject’s tolerance.

    How is semaglutide delivered?

    Semaglutide is delivered subcutaneously, most commonly into the fatty tissue of the abdomen.

    How do I reconstitute semaglutide?

    Semaglutide that is shipped in freeze-dried powder form must be reconstituted with bacteriostatic water. Reconstitute semaglutide by extracting the correct amount of bacteriostatic water and inserting the solvent into the semaglutide vial, allowing the water to slowly enter and then swirling the solution until completely dissolved.

    Semaglutide for Sale | Verdict

    Semaglutide is a GLP-1 receptor agonist that promotes weight loss, helps with the management of type 2 diabetes, and works to reduce cardiovascular risk in diabetics and overweight subjects.

    For researchers who struggle with obesity or diabetes despite adopting healthy eating and exercise habits, semaglutide can be a life-changing addition to their treatment regimen. Though it is generally well-tolerated and safe, semaglutide should be administered at a low dose and gradually increased over time.

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    1. Mahapatra MK, Karuppasamy M, Sahoo BM. Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes. Rev Endocr Metab Disord. 2022;23(3):521-539. doi:10.1007/s11154-021-09699-1
    2. Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art. Mol Metab. 2021;46:101102. doi:10.1016/j.molmet.2020.101102
    3. Ard J, Fitch A, Fruh S, Herman L. Weight Loss and Maintenance Related to the Mechanism of Action of Glucagon-Like Peptide 1 Receptor Agonists. Adv Ther. 2021;38(6):2821-2839. doi:10.1007/s12325-021-01710-0
    4. Aroda VR, Ahmann A, Cariou B, et al. Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials. Diabetes Metab. 2019;45(5):409-418. doi:10.1016/j.diabet.2018.12.001
    5. Rodbard HW, Dougherty T, Taddei-Allen P. Efficacy of oral semaglutide: overview of the PIONEER clinical trial program and implications for managed care. Am J Manag Care. 2020;26(16 Suppl):S335-S343. doi:10.37765/ajmc.2020.88554
    6. A quick guide to the STEP trials. Published February 11, 2021.
    7. Kennedy C, Hayes P, Salama S, Hennessy M, Fogacci F. The Effect of Semaglutide on Blood Pressure in Patients without Diabetes: A Systematic Review and Meta-Analysis. J Clin Med. 2023;12(3):772. Published 2023 Jan 18. doi:10.3390/jcm12030772
    8. Smits MM, Van Raalte DH. Safety of Semaglutide [published correction appears in Front Endocrinol (Lausanne). 2021 Nov 10;12:786732]. Front Endocrinol (Lausanne). 2021;12:645563. Published 2021 Jul 7. doi:10.3389/fendo.2021.645563
    9. Semaglutide Responsible Use | Official Website. novoMEDLINK.
    10. Bethel MA, Patel RA, Merrill P, et al. Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis. Lancet Diabetes Endocrinol. 2018;6(2):105-113. doi:10.1016/S2213-8587(17)30412-6
    11. https://www.Drugscom. Semaglutide Dosage Guide + Max Dose, Adjustments..
    13. How to Get Semaglutide: Eligibility, Cost, Insurance, and More. Healthline. Published June 21, 2023.
    14. Semaglutide Shortage Prompts FDA Warning to Patients, Providers. HCP Live. Published June 7, 2023.
    15. GOODRX. Prescription Prices, Coupons & Pharmacy Information - GoodRx. Published 2020.


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