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myhealthexplained.com - What is Ozempic (Semaglutide) - My Health Explained

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Video Transcript for Ozempic video

Today, I would like to talk about Ozempic and explain how Ozempic or Semaglutide works, what the effect is and what you can likely expect, the side effects and essentially how to take it and get the best and the most out of it. My name is Dr Sultan Linjawi. I'm a certified Diabetes Specialist and Endocrinologist and this is what I do for a living. I provide education around new diabetes treatments and old diabetes treatments, to people around the world. So let's talk about Ozempic, or Semaglutide. So Semaglutide (Ozempic) is a once weekly injection for people with diabetes. It is something called a GLP1 analogue and I'll explain a little bit what a GLP-1 is. But in essence it looks very similar to a naturally occurring chemical that we all produce that helps us regulate our appetite as well as our blood sugar levels and this treatment is for people with Type 2 diabetes where it has been tested and investigated fairly heavily. It is not approved for people with Type 1 diabetes and shouldn't be taken in women who are pregnant or breastfeeding and it is ill-advised at the moment to be using it in children.

So what is a GLP-1?

Well GLP-1 is an extremely powerful chemical that is produced in response to eating by our gut and it does a number of things, but there are four main actions. So the first is that when the chemical is released it circulates into our system and it gets to our brain and there it leads to reduced appetite. It is the thing that people experience when they have eaten too much where suddenly they feel they are just overfull. That sense of sickness, or fullness, that you might feel if you have gorged yourself is actually GLP-1 hitting the brain and saying that is enough. Now, some people seem to produce fantastic GLP1 responses that are really effective. Generally, people that are thinner, they stop eating a lot more quickly. But we know that in people with Type 2 diabetes that sense is often impaired and if you give someone GLP-1 you can switch off the appetite to some extent and achieve some weight reduction.

Now how else does it work in the body?

Well, in the liver, it reduces the amount of glucose, or sugar, that is released by the liver. The normal situation for a person would be to release sugar into the circulation unless you don't need it. But in Type 2 diabetes, there is impaired release of glucose out of the liver. Continually the stores are being released into the circulation even though the blood sugar level is elevated. So the third mechanism of action is around slowing stomach emptying and slowing what we call gastric emptying that process leaves food in the stomach for longer therefore there is less necessity to go looking for food and finally, the action is around the effect on the pancreas where GLP-1s both increase the amount of insulin that is produced as well as increase the amount that is released. And the interesting thing about it is that that is predominantly when the blood sugar is elevated. In other words GLP-1s and there are a range of these treatments all have an effect which is predominantly around high sugars and if the sugar becomes low, the effect is switched off, and it is the reason we see very low rates of low blood sugars so called 'hypos', or hypoglycemic episodes that occur with GLP1 treatments.

So if you are on Ozempic or Semaglutide what dose should you use?

Essentially there are two doses that are prescribed and talked about. One is 0.5mg and the other one is 1mg. And the way we take it, well this is how you start taking it. In the clinical trials, it was a weekly injection and they started at 0.25mg a week and that was for 4 weeks. At the end of 4 weeks, predominantly that was around getting used to the drug, at the end of 4 weeks, the dose was increased to 0.5mg weekly. And for many people that is an extremely effective dose. In fact for some people, the lower dose is still going to be highly effective in terms of 0.25mg and there may not be a need to increase the dose even though the clinical trials suggested that was what needed to happen.We do not know what the actual effect of 0.25mg is.

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Now if 0.5mg isn't enough and you have waited some time and the blood sugars are still not where they need to be, then we do have the option of increasing it to the 1mg dose. So it is a step process, 0.25 initially for 4 weeks to get used to it, then 0.5mg, and if that is the dose for you, fantastic. If you need escalating further, then up to 1mg. But I want to say this, because I think it is important. Ozempic (Semaglutide) will take 5 weeks to get going and get into your system. It won't reach, what we call steady state, until that time. Its main effect won't be felt for 12-24 weeks. So if you think, I'm going to take this drug and in 2 or 3 days my sugars are going to be perfect that's not how it works. So you have to wait for its effect to have so you can make those judgments about when you need to increase the dose and if you stop it, it clears the system or the body, in about 4 or 5 weeks.

So how does Ozempic (Semaglutide) compare to other GLP1 therapies?

Well I think it is just worth mentioning there are a lot of GLP1 treatments available at the moment and some of them you will be familiar with, there are weekly versions and daily versions. The weekly versions that we are looking at are things like Trulicity, which is called Dulaglutide, or Bydureon, which is known as Exenatide Extended Release and then we have daily versions and daily versions would be Liraglutide, or Byetta and maybe the only other agent that is used a bit is Lixisenatide. So we have quite a bit of options in terms of GLP1 treatments and most of those options are being tested and looked at.

So the first study I want to show you, is this one.

This was looking at whether or not Ozempic worked, and it was comparing Ozempic to a placebo, so a dummy injection and across the whole of this image, the light blue bars are the low 0.5mg dose of Semaglutide (Ozempic) and the dark blue bars are 1mg. And you can see that both of the Ozempic (Semaglutide) doses, lowered HbA1C by around 1.5-1.6% compared to placebo incredibly effective. Compared to Bydureon or Exenatide Extended Release the 1mg dose lowered the HbA1C by about 1.5% compared to Exenatide at 0.9% so there was about a 0.6% reduction but Ozempic was superior. They compared it to insulin. In this case insulin glargine or Lantus. You can see whilst Lantus was effective at lowering the blood sugar by about 0.8% of an HbA1C again there was superiority in the 0.5mg and 1mg dose of Semaglutide (Ozempic). And the only drug that really got close, and it really did get very close, and is a reasonable comparison is Trulicity, or Dulaglutide. And there are two different doses of Trulicity as there are two different doses of Ozempic but to both ends it looks like Ozempic was superior by about 0.4mg. So that is impressive. Because Trulicity is a very, very effective drug for many, many people.

What about weight loss?

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We talked about the fact that these drugs are exceptionally impressive at weight reduction and in fact out of all the drugs that we have to date in the GLP1 category Ozempic (Semaglutide) seems to be the most effective around weight reduction. And if you just look at this graph, anything above the line, is a weight increase. So you can see that in the middle there with the little green mark there around insulin glargine (Lantus) which put on a bit of weight. But across all the other drugs, and the other trials, there was weight reduction and consistently it looks like there was a weight loss of between 3.5kg - 6.5kg favouring Ozempic with the bigger weight loss seen in the higher dose.

So what are the side effects of Ozempic(Semaglutide)?

Well, the common side effects are nausea, diarrhoea, vomiting, abdominal pain, and decreased appetite. And that is what was reported, but in fact if you talk to people who are using it, it is that sense of fullness, that queasy feeling that you have if you have eaten too much. Imagine going to a wedding and just stuffing your face and then someone saying "would you like another dessert?" and just thinking no I can't eat anymore. That is the sensation that you get with GLP1 therapies and it is experienced by about 10-20% of people but the vast majority of these symptoms settle after around about 8-12 weeks in most people and if somebody were in a situation where they felt nauseated there is no reason that they need to escalate from 0.25mg up to 0.5mg until that nausea has settled. Because it is a very powerful drug and it would be a shame if we gave up on it because the side effects were bad in the first week or two and we didn't find a way to persist.

Now there are a few serious side effects that are noted.

So there was a concern with a GLP-1s around inflammation of the pancreas that is extremely rare, low blood sugars are unlikely, but possible, and of course, there are allergic reactions.

So there is Ozempic (Semaglutide).

A new treatment that is being launched all over the world that is for people with Type 2 diabetes, that seems to not only lower blood sugars but also in lowering blood sugars leads to some weight loss. There is some good evidence also that in people who have cardiovascular risk factors, in other words, people who are either susceptible? to heart attacks and strokes or people who have had one in the past, this reduces the likelihood of having a further event by around 25-26%.

That is in common with a number of other GLP-1 drugs.

So these are really powerful agents that are really helping us, as healthcare professionals, provide great care and outcomes for people with diabetes and certainly a great tool if you have diabetes to help you moving forward because with the benefits of weight loss and the reduction in blood sugars being so powerful and the potential benefit of reducing heart attacks and strokes this is part of the future of diabetes that is here right now.

myhealthexplained.com - What is Ozempic (Semaglutide) - My Health Explained

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