What Semaglutide Does and How it Works

What Semaglutide Does and How it Works

The Hollywood Sizzle

Semaglutide is one of the most popular weight loss compounds around right now.  Many Hollywood celebrities are even eyeing this apparent "miracle weight loss drug".  According to a daily mail article not only are they taking it, but they are willing to spend upwards of £1500 a month on it.  While the reports are mixed some say the Kardashian family has even dabbled in using the drug along with many other celebrity figures. More and more doctors are getting requests from their clients to prescribe them this drug.  While everyone has been caught up in the semaglutide storm I think it is important we take a stepback and understand how it works and what it is doing to our body.


1 Class Mechanism of Semaglutide

Semaglutide belongs to a class of drugs called Glucagon like Peptide-1 (GLP-1) receptor agonists.  In the clinical world it can be prescribed as a stand alone drug or in conjunction with other therapies.  It is typically prescribed for people with diabetes although is being looked at as a drug for weight loss as well.  Semaglutide has done well with its safety testing and has been shown to be safe and effective.  First though we must look into what GLP-1 is. GLP-1 is a major incretin hormone.  Incretins are a group of hormones that inhibit glucagon secretion and stimulate insulin secretion.  GLP-1 has many different mechanisms it partakes in like augmented insulin secretion, inhibition of glucagon release, suppressed hepatic gluconeogenesis, and reduced appetite.  Semaglutide essentially improves how well these incretins work by activating the GLP-1 receptors  GLP-1 receptors are also found all throughout the body including pancreatic beta cells and the brain.  The receptors in each region have different purposes with the ones on the pancreatic beta cells used more for insulin secretion and the ones in the brain contributing to its appetite suppressing effects.  So to make it understandable for the everyday person the way semaglutide works is by agonizing or activating the GLP-1 receptors which are responsible for helping lower blood glucose levels and controlling appetite.  There are a whole host of other things but these are the main ones we will focus on for today. 

Now let's look into the pharmacokinetics of Semaglutide  

For those who are not aware, pharmacokinetics is essentially how a drug moves in your body.  So when you take a drug how well does your body absorb it, how does the drug distribute and metabolize, and then the excretion of the drug.  When using it as an injection it comes with 89% bioavailability, compared to the .4-1% bioavailability you get when you use it orally.  This basically means it is nearly useless when taken orally as our body can barely absorb it.  It takes 4-5 weeks to achieve stable serum state concentrations with it and 1-3 days to achieve maximum concentrations.  The study I was referencing utilized 500 mcg or 1g once per week to reach a steady state.  It comes with a half life of around 7 days meaning it only has to be injected once per week which is really amazing, and makes it far easier to adhere to then something that has to be injected daily.


The next question: What can Semalutide do? 

The main benefits people will note when they use Semaglutide is a huge reduction in appetite. This is not the only way, but one of the major ways it can help the user lose weight.  When I say this thing kills your appetite I mean it really kills your appetite.  This is in my eyes one of the strongest if not the strongest appetite suppressants on the market today.  As obvious as it sounds when our appetite is lower we are less likely to eat leading to more fat loss and better health.  The second thing that Semgalutide can do is have a profound impact on blood glucose.  Studies have shown it is highly effective in reducing markers like HbA1c.  HbA1c is a test that measures your average blood sugar levels over the past 3 months.  Proper blood glucose levels are essential not for helping people lose weight, but it is essential in overall health and well being.  When blood glucose levels are kept in range we are at much less likely to have diseases such as diabetes which can negatively impact the heart, nerves, and kidneys to name a few.


To summarize, Semaglutide is a powerful diabetic drug that can have profound impacts on weight loss.  Semaglutide exerts this effect by agonizing GLP-1 receptors which are receptors that can be found across the body.  This leads to it having a variety of effects like being able to lower appetite (due to GLP-1 receptors in the brain) and being able to help secret insulin through GLP-1 receptors on the pancreatic cells.  The research shows that the drug should be injected once per week based on its 7 day half life.  The doses used in the studies I referenced were 500mcg and 1mg per week but these are not prescriptions or recommendations just merely the ones that have been used in the studies. 


  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 Jun;23(3):521-539. doi: 10.1007/s11154-021-09699-1. Epub 2022 Jan 7. PMID: 34993760; PMCID: PMC8736331.
  2. Hall, Sylvie et al. “Pharmacokinetics and Clinical Implications of Semaglutide: A New Glucagon-Like Peptide (GLP)-1 Receptor Agonist.” Clinical pharmacokinetics vol. 57,12 (2018): 1529-1538. doi:10.1007/s40262-018-0668-z
  3. Crabtree, Thomas S J et al. “Injectable semaglutide and reductions in HbA1c and weight in the real world in people switched from alternative glucagon-like peptide-1 receptor agonists.” Diabetes, obesity & metabolism vol. 24,7 (2022): 1398-1401. doi:10.1111/dom.14701
  4. https://diabetesjournals.org/diabetes/article/64/3/715/40332/Hepato-Incretin-Function-of-GLP-1-Novel-Concept
  5. https://www.dailymail.co.uk/health/article-11236583/Celebrities-spending-1-500-month-diabetes-drug-incredible-weight-loss.html
  6. Smits MM, Van Raalte DH. Safety of Semaglutide. Front Endocrinol (Lausanne). 2021 Jul 7;12:645563. doi: 10.3389/fendo.2021.645563. Erratum in: Front Endocrinol (Lausanne). 2021 Nov 10;12:786732. PMID: 34305810; PMCID: PMC8294388.


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