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How does Semaglutide work?


Semaglutide is a drug that is currently licensed for the treatment of type 2 diabetes, either via a subcutaneous injection (Ozempic), or as a daily tablet (Rybelsus).


However, during clinical trials, it was discovered that semaglutide can also help with weight loss in adults with a BMI of over 30. It is currently going through more clinical trials with a view to being approved as a drug for obesity as well as for type 2 diabetes.


One question that’s often asked when it comes to semaglutide and weight loss is “how does it work?”


Semaglutide differs to other popular weight loss treatments such as orlistat due to the way it works in the body. Where orlistat helps to remove excess dietary fat, semaglutide helps to mimic a hormone that’s produced in the gut after a meal, meaning that it can reduce your appetite by making you feel fuller for longer.


Glucagon-Like Peptite 1 (aka a GLP-1)


Before we talk about how semaglutide can help with weight loss, we first need to understand what GLP-1 is.


GLP-1 is a hormone that’s naturally produced by our bodies in the small intestine when we’ve eaten a meal. It plays a part in helping us to feel satisfied after eating. However, natural human GLP-1 doesn’t last that long, which is why we often feel hungry or peckish a couple of hours after a meal.


GLP-1 is an incretin, which is a type of hormone that helps to reduce blood glucose levels and stimulate the secretion of insulin. In people with diabetes, the GLP-1 produced by the body isn’t enough to control glucose and insulin levels, so drugs that mimic the hormone, such as semaglutide, are used to boost the body’s natural response. As semaglutide is a synthetic version of this hormone, it’s usually called a GLP-1 receptor agonist, or alternatively, an incretin mimetic. This means that it mimics the hormone we produce naturally, but with a few alterations, which explain how Ozempic is able to help people to lose weight.


How does it work for weight loss?


We’ve already talked about how semaglutide (the active ingredient in Ozempic & Rybelsus) is a synthetic form of GLP-1, but what does that mean for weight loss?


As semaglutide is structurally modified, it means that it lasts much longer than GLP-1 that naturally occurs in your body, hence why you only inject it once per week. This modification means that semaglutide is prevented from being broken down by an enzyme in the blood, helping to be a long-lasting and effective treatment.


Ozempic and other semaglutide drugs such as Rybelsus are around 95% similar to human GLP-1, with the modifications helping it to last longer in the body. As a result, gastric emptying (or the digestive process) is delayed, making you feel fuller for longer, and after a smaller amount of food. Essentially, through a complex effect on the nerves that control energy expenditure and food preference  it helps to suppress your appetite, leading you to consume fewer calories.


When gastric emptying is delayed, food that you’ve consumed stays in your stomach for longer, giving you a feeling of satisfaction that lasts longer than if you were relying on the body’s natural production of GLP-1 alone. When you feel full or satisfied, you’re less likely to snack or feel hungry between meals. For many people, this can be the help that they need to reduce their calorie intake to start losing weight and becoming healthier.


It’s a common misconception that weight loss is about willpower, as there are many factors that can contribute to excess weight or a high BMI, such as underlying health conditions, genetics, diet and environment. However, what we do know is that a calorie deficit or reducing your calorie intake can go a long way towards helping those that struggle with excess weight. By taking semaglutide either weekly as Ozempic, or as a daily tablet like Rybelsus, you may be able to reduce the amount of food you consume, which is particularly helpful if you find that you eat large portions, have a big appetite, or if you snack a lot during the day.


Ozempic has also undergone clinical trials known as the STEP (Semaglutide Treatment Effect in People with obesity) trials; this time as a treatment for obesity. Results from these trials show semaglutide to be an effective treatment for weight loss in those with obesity, more so than other, similar drugs such as Saxenda. 


Significant reductions in appetite


During clinical trials for semaglutide when it was being reviewed as a treatment for type 2 diabetes, it was noticed fairly early on that it also had an impact on weight for participants. A similar drug called liraglutide (Victoza) which is also produced by Novo Nordisk also had this effect several years ago – the difference being that liraglutide is a daily injection whereas semaglutide has a longer elimination half-life, allowing it to be injected once weekly instead of daily.


Researchers found that when compared to Saxenda, Ozempic helped participants to lose more weight within the same timeframe.


Recently, Novo Nordisk conducted a trial with semaglutide in the STEP program, which evaluated how efficient semaglutide injections are when it comes to treating obesity in adults with a BMI of over 30 (without diabetes). Published findings from this study are promising, with results showing a mean loss of around 15% in body weight from the start of the trial to the end in the semaglutide 2.4mg group, compared to just a 2.45 reduction in those taking the placebo. A third of participants taking semaglutide lost at least 20% of their starting weight, which equates to around a 44lb total loss if a participant’s starting weight was 220lbs.


These significant findings relating to weight loss are thanks to the mechanism of the drug that helps to slow gastric emptying, as this is what causes such drastic changes in appetite levels and calorie consumption. The STEP trials show that semaglutide injections absolutely help people with obesity to lose weight due to the stark differences in findings between the semaglutide groups and the placebo groups.


In addition to helping participants to lose weight, it was also found that semaglutide injections can help to reduce blood pressure and other obesity-related conditions. This is in addition to the already known fact that Ozempic can help to reduce the risk of a heart attack and other cardiovascular events in adults with Type 2 diabetes.

Click here to read the study in more detail.

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