How Ozempic Works For Weight Loss | Jason Fung

I'm DrJason fun today we're going to talk about OIC the weight loss drug that's sweeping North America and how it works and what implications it has for weight loss and it's coming right [Music] up OIC which is the drug known as semaglutide is part of a drug class called The glp1 Agonist group meaning that it stimulates a hormone called the glucon like peptide one receptor or glp1 and this drug class was initially discovered in the saliva of the Gila monster this drug class was actually approved in 2005 by the FDA and there was some modest weight loss about 5 1/2 lbs so it wasn't great but it was definitely there uh next came lorag glutide which could be taken once a day and again it was was easier and it did have a little bit of weight loss um but it was really only about 8 to 10 lbs so again the drug companies continued to work on this molecule to make it even easier so instead of a once a day injection they created a once a weak injection and that became stide which became OIC and at a higher dose is called wovi the amount of weight loss was a bit of a revelation in fact the uh step one study which was published in the New England Journal of Medicine showed that people could lose about 15% of their body weight and actually keep it off so how does the drug work well there was really three main effects of this drug none of which were really related to the insulin secretion that was initially thought to be how it worked one is that it caused satiation which means that when you ate it made you full one of the effects is is of of this drug is to delay gastric emptying so the stomach normally holds your food and mixes it up with stomach acid and then slowly releases it into the small intestines for digestion if the stomach is very full that is you've eaten a lot or the stomach simply isn't emptying then you activate stretch receptors in the stomach and that tells your brain that hey you're full you shouldn't be eating anymore the second major effect is that it causes a tidy which is the sensation of being full uh and not feeling hunger and here the effect is mainly in the brain the glp1 has receptors in the brain areas known uh a sub fornical organ which is along the third ventricle and at that area it has a very weak bloodb brain barrier so that when your intestines release the gp1s it can then act in the brain and it's not going to get blocked by that bloodb brain barrier and the third major effect is vomiting so again in the brain there is a region called the area of PSTA and it's very very dense in gp1 receptors and when activated it makes you vomit so all three of these uh sort of side effects which is delayed gastric emptying causing satiation uh increase uh satiety due to the direct effect and also vomiting all of those would basically cause you to have uh this effect of not wanting to eat the number of people that had side effects on this drug it was a rather stunning 89% of uh people actually had side effects so nausea had 44% in the treatment group versus 17% in the placebo and this really explains a lot of the effect of uh the drug that is if you're busy talk bossing your cookies well you're not going to think oh wow this would be a great time to eat a little stinky blue cheese for example the instinct is to not eat and when you don't eat your body is going to use those sorts of calories that it has stored which is glucose and body fat so therefore you see that it's a very good drug to reduce blood glucose for the treatment of type two diabetes and also for uh obesity and what we find is that people do in fact fact uh lower how much they eat by almost 1,000 calories a day and the effects are quite widespread that is there's there's multiple effects if you look at the number of daily meals that they take like how often people are eating it's down by about 0. 6 meals per day if you look at how often they snack it's down by about 1. 4 snacks per day they also tended to increase their exercise and they changed the foods that they were eating so if you're less hungry then it's a lot easier to make those healthy choices and you see this in the study that was done uh in 2023 where they found that they ate a lot more fruits and veggies and chicken and fish and ate a lot less cookies sugary drinks and candy and really no matter what diet you think is effective that's a good switch people also ate out a lot less 63% overall with a a a a whopping 73% % decrease in fast food visits after all why would you want to spend money eating out if you don't even feel like eating um if you look across the macronutrients that is the carbs the proteins and the fats well that's where you saw all of them decrease but specifically in the carbohydrates the most and also in the fat so what does OIC really teach us about weight loss is it all about the calories is it just because of the calories and the answer here is a definite no you have to remember that there's lots of effects there's decreased meal frequencies decreased snacking decreased carbohydrates there's less eating out less fast food so you can't simply say that it's due to the less in calories it could be any of those other effects and you got to remember that OIC does not directly affect calorie intake what it does is it controls the hunger which then reduces the calories which causes the weight loss but because it controls the hunger what you're doing is attacking the root cause of the problem because if you're really hungry and you simply eat fewer calories and you're still hungry well that's not a very sustainable situation because then you're hungry all the time and when you're hungry you're going to want to snack or you're going to eat more frequently or you're going to make those bad choices so really OIC teaches us that is really about controlling the hunger and not the calories and we see this in other drugs too you see this in nicotine for example uh it also is well known to reduce hunger in fact uh studies going back hundreds of years have shown that uh even native peoples had used uh tobacco as a way to cut down the hunger pangs when you smoked you simply didn't want to eat as much and you see this effect in weight smokers Uh current smokers weigh less than uh former smokers and you can actually track that effect as they quit smoking their their their weight starts to go up because again it's about controlling the hunger which controls the calories the question is then what controls hunger and some people think that hunger is really just about having no food in your stomach that's not true it's actually a hormonal State because if you look at circadium studies of hunger such as this one for example what you see is that um in Lots when you take a lot of people and measure how the the the time of day that they are the most hungry H it it is 8:00 p.

m. in the evening if you look at the time that they are least hungry it is 8:00 a. m.

in the morning yeah 8:00 a. m.