Doctor Reveals Truth About Semaglutide & Other Weight Loss Drugs | Kyle Gillett M.D.

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we live in a world where all the information in the world is at our fingertips and sometimes it's absolutely paralyzing and when you start getting down to the granular of weight loss intervention and weight loss drugs and pharmaceuticals I really like to leave it to the experts so I've got Dr Kyle Gillette here board certified Family Medicine physician as well as obesity medicine physician a guy is a wizard when it comes down to this stuff so first of all thanks for hopping on thank you my pleasure diving right in we're going to talk about the five most popular weight loss drugs that are being used presently here as of 2023 so once you take it away what's number one you have to check out Bond charges infrared sauna blanket after this video not a lot of people have room to put a sauna in it's kind of a pain in the butt I love having my sauna but I had to run a continuous circuit for it I had to run a dedicated electrical circuit that costs money that takes time that takes space a nice infrared sauna blanket is totally portable and this Bond charge one has very low EMF in fact they were kind of surveying around if it's the lowest EMF on the market but also it gets up to 176 degrees and since you're laying inside of a blanket you're right next really really close to the infrared light which means that you're getting a bigger effect than if you were further proximity in a standing infrared sauna like a regular sitting one I think the best part about it is the fact that you can travel with it you may not want to bring it on a plane but if you're going on a road trip or something like that it's easy to pack in your car it fits in something you know a couple feet it just kind of like rolls together but you get all the benefits of Asana you get that better recovery you get that better sleep that a lot of times come with comes with sauna you get those heat shock protein effects so I definitely recommend so there's a special link and a code down below that'll save you some cashola if you want to try this one out definitely recommend I've tried a lot of them and a lot of them are flimsy and cumbersome I love the quality of this Bond charge one it's easy to open up and scrub clean if you've got really sweaty in it too so it's not nasty that's what I really like about it so the link down below already great price plus if you use that special code you can save even more so check out bonchar's infrared blanket down below in the description all right let's talk about summer glute side first again briefly um this is a glp1 receptor Agonist there's a shortage of it because it's so popular so it probably deserves the number one spot and it's an in [ __ ] so there's a lot of mechanisms other than just appetite suppression it's an insulin sensitizer it slows gut Transit it also helps your pancreas work better so there's a lot of different mechanisms there is also risks of course for example buildup of like bile cholestasis estrogen and thyroid carcinoma risk if you happen to be someone who's at risk of that we don't really know how concerning that risk is but potentially it is risk but that's semi-glutide I guess we could just name off all five right now and then let's talk about them perfect number two I'd say is metformin so of course Very Old School drug it is an insulin sensitizer as well it also has multiple mechanisms of action it's best application for weight loss is in type 2 diabetics and also sometimes in type 1 diabetics as well it is not without risks we could talk about it for hours but it is certainly very helpful intervention even for losing body fat in some individuals especially individuals with very high weight High lean body mass and high body fat number three I suppose we could consider bupropion and number four Naltrexone those kind of go together there's a combo pill with both bupropion and Naltrexone that is a dopamine reuptake inhibitor plus an opioid receptor antagonist so these do work on appetite they work a lot in the hypothalamus it's also dopaminergic so it has to do with like Reward Center a great candidate for something like this would be an individual that could benefit from bupropion otherwise perhaps for nicotine cessation perhaps for like its mood or positive mental effects no Tropic effects a lot of people with ADHD are put on this medication as well and then people who eat a lot at night so night eating syndrome sleep eating syndrome or are more rare but in general they benefit more from like the the CNS effects of these weight loss medications they can also help regulate inflammation of the gut specifically LDN so it binds the same receptor as things like gluten or casein or even Kratom except it does the opposite thing of those three and then I guess we have one more maybe two more we could put Phentermine on it a stimulant that used to be used pretty often they now have it in a combination of something called Topiramate and this is not as common but there are some people who are particularly good candidates for it people who have epilepsy or a history of seizure use because it can decrease the chance of that people who have lots of migraines you don't want to use this in people with kidney stone history in addition another good candidate for it could be people who are addicted to pop it can make carbonated beverages taste terrible so if someone's having trouble with zero liquid calorie diet or drinking a lot of especially like full calorie sodas they could be a good candidate gotcha well let's jump into it so we kind of covered glp-1 a little bit we have a full video breakdown on that so we'll spare the time on that if you want to watch that there's a link down to it in the description but next up was going to be metformin now interestingly so I thought metformin was really only going to be used in people that were having issues modulating glucose and dealing with diabetes and insulin resistance you're telling me that it's actually being used as a weight loss drug that's news to me yeah so metformin is extremely interesting because it is going to have multiple mechanisms of potential benefit for example if someone has an extremely low shbg sex hormone binding globulin it's the protein that binds androgens and estrogens Metformin can help bring this up if someone has a normal shbg it likely won't affect it at all but if it's very low it certainly can raise it and this can help balance the Androgen to estrogen ratio especially in individuals that have like effects of hyperandrogenism Downstream to the Androgen receptor not to get too specific into that we can some other time but essentially if they need that hormonal effect of an increased shbg it can be a beneficial intervention in addition it can help increase The Binding peptides that bind I gf1 which is insulin-like growth factor one so if there's excess growth hormone for example in type 1 diabetics or excess igf-1 and some people with insulin resistance then it can help balance out these risks and it may or it is theoretically going to be an anti-proliferative agent so it could help prevent tumor growth in that population as far as its weight loss effect it is an insulin sensitizer they rename The receptors they used to be called the glute 2 and glut4 now they have different names of them solute co-transporter something to them because it's not just a glucose transporter but anyway for the solute co-transporters both in the liver and in the periphery for example in you know like somatic muscle then they're going to help with the uptake of glucose given the same level of insulin so people with very high fasting insulins can be a good candidate for this because you're thinking about the trade-offs of Metformin well if you give it to someone who's metabolically healthy which is likely between about six and fifteen percent of the population in this country then it will likely have no benefit and may even have some detriments given that it affects some of the downstream Pathways from not only the Androgen receptor but also different Pathways that lead to mtor activation however if you're thinking about this medication for weight loss then presumably you're probably not metabolically healthy likely have a high body fat percentage and it can also be used for people that are coming off some agglutide that still needs something um with like less confounding variables to help as an insulin sensitizer that makes perfect sense so if someone has chronically high levels of circulating insulin you know and they're also dealing with high levels of body fat I mean it's kind of go hand in hand so you start controlling one you can hopefully control the other I mean and for those that are watching that maybe don't have a little bit of background I mean if insulin is consistently circulating that is going to inhibit the action of hormone sensitive lipase it's going to inhibit what's called lipolysis so essentially the actual mobilization of fats the actual snipping of a fatty acid off of a triglycerol to be able to be utilized for fuel in other words in a very colloquial sense it really can inhibit fat loss especially if you already have a lot of body fat on hand so by potentially improving sensitivity you might be able to sort of disrupt this a little bit and there's definitely a benefit of less glycosylated proteins whether it's hemoglobin or albumin or fructosamine when you have nutrients whether it is triglycerides or glucose inside the cell and again triglycerides is glycerol backbone with Three fatty acids methods kind of your main source of fat in the blood and then you have your glucose which is kind of the main source of carb in the blood if you will metformin will help with cellular intake of both of those things so um yeah if there's think of it as like your combined pool of triglycerides fasting plus glucose fasting or I suppose if you're a keto diet or maybe keep maybe blood ketones as well but basically a pool of those things and then if it is on the higher end better candidate for something like metformin or berberine I also posted a lot of info on my Instagram about both metformin and berberine just because there's so many nuances and we probably both get this question all the time definitely definitely interesting and I'll touch on one thing that was very important that you mentioned I think people forget the fact that High circulating amounts of lipids are a problem too and the reason that this has become an area of confusion is because you have the low carb Community I'm probably guilty of confusing people on this too but you have the low carb community and you think okay fats in the bloodstream are good this is what we want because it means we're going to burn them no it doesn't necessarily mean that in fact when those are circulating that is a problem too and it's usually an issue that you see in diabetics or insulin resistant people so just important to know I like to check a Homa IR which is a ratio of fasting insulin to fasting glucose and also an lpir or an NMR lipoprofile which is six different markers including triglycerides and particle sizes and between the two of them you can estimate your insulin resistance due to carbs and insulin resistance to the fats yeah that's a very important thing okay let's touch on that for just a second so insulin resistance can still be caused by excess fats circulating as well correct now this mechanism is is it just because fats are sort of impeding the action upon the insulin receptor or I'm assuming there's multiple different ways but I've seen research that okay especially in over nutrition when people are eating a lot like excess consumption of saturated fats can be almost as bad if not equally as bad as excess amounts of sugar in the sake of over nutrition are they working upon the same pathway um there are similar tangential Pathways so think about it as a dual fuel vehicle you have maybe compressed natural gas and you have gasoline both so you can use both of these energy substrates for the cell but if you're putting fuel in the car at some point you're just putting so much fuel in that it will either overflow or just be in a higher level than you would want in the car so for fat specifically there's a couple different ways that you transport fats around vldl is one of them vldl is one of the ways that you carry around fats that are endogenously synthesized in your body and then chylomicrons which is one way that you carry around fats or like lipid-based particles that come from the diet so a lot of that is just due to genetics for example if you have an APO E2 apoe is APO lipoprotein e there's um there's a couple different uh like Snips that you can have but basically you get one from your mother one from your father you can be you can have two three and four so you can be a four four Chris Hemsworth and Limitless was famously a four or four so that's your Alzheimer's risk if you're a 2-2 then that can carry a risk of what we call like familial hypertriglyceridemia or it can be so high like in the thousands that it's even a risk of pancreatitis inflammation of the pancreas so a lot of it's just genetic and it's determined by your body's ability to process both fats that are eaten in endogenously synthesized ones interesting and then there's sort of another layer with the have you heard of metabolic gridlock before sort of at a mitochondrial level so in the case of over nutrition in one particular setting you know a lot of this is still rodent model stuff but it's very interesting or essentially if you're over feeding at both at you know carbs and fats at once you do reach a point especially people that are intermittent fasting where they're maybe trying to load like two or three thousand calories with one meal doing one meal a day where essentially the uptake of fuel substrates really just it gets confusing the body's just good call a metabolic gridlock where you can only take up so much at one particular point in time and actually utilize it and usually it leads to kind of an inflammatory Cascade that happens further on down the line but anyway that's enough of a tangent so moving on to number three okay we've got so we've got semi-glutide glp-1 we've got metformin and what's number three uh number three was low dose Naltrexone and Number Four Is bupropion but um one company puts them together into the same drug so uh the brand name of that drug is contrave bupropion also known as Wellbutrin has been used for quite some time for not fat loss or obesity but it was used for many things that are like Cravings or addiction for example cravings for nicotine um it is a dopamine receptor reuptake yeah it's a selective dopamine receptor uptake reinhibitor so you're going to reuptake less of your dopamine so your dopamine can work on the hypothalamus to potentially decrease Cravings but it can also improve mood and it can also improve ADHD symptoms so a lot of adults with ADHD take this medication it's combined with a medicine called Naltrexone classically prescribed like 50 milligrams or even more than that for things like alcoholism or even for sometimes for like nicotine as well but it's interesting because it's an antagonist at the MU opioid receptor which is the opioid receptor that things like gluten and casein and Kratom will bind to so it can help with gut transit or even decrease gut inflammation in addition it's going to work on the brain stem including the hypothalamus as well so this combination is often used in people with food addiction or carb addiction or liquid calorie addiction or people that eat a lot in the evening there's not necessarily a perfect candidate for it but it does come with a risk of if someone has had a seizure before it can precipitate seizures more likely so it lowers the threshold of having a seizure what about feedback loops when you come off of this stuff not as worrisome as coming off a glp wants really yeah not as worrisome the um one of the interesting things about low-dose Naltrexone compared to I guess high-dose Naltrexone is low dose in general is between about 0.5 and 8 or maybe 12 milligrams is that other inputs can supersede it more easily for example if you break your leg and you go into the ER if you need some morphine then it's not going to interact with that as much and then it's also going to not like overly sensitize the receptor so opioid receptors dopamine receptors and Gaba receptors are classic for being sensitized or desensitized very quickly but at lower doses it is not as concerning that being said all medications and even I would say all supplements all efficacious supplements that can aid for fat loss are going to have a slight withdrawal rebound risk interesting so but I mean in that point though if they can be synthesized easily too then as long as you can maintain good lifestyle for a relatively short period of time I don't know how long that would be but it sounds like you can bounce back if you can just keep it under control for a while yes yeah is it tough to give an adequate time frame like if someone were to go on these compounds and come off how long would they have to be grinning and burying it so to speak until things are starting to come back to normal probably two months of very close monitoring for most of these compounds and probably six months for a glp-1 especially if you try to come off without weaning the dose down first okay all right and moving into number five what's number five we could talk about Phentermine for number five there's a couple combos you mentioned Topiramate there's a combination of like a low dose Phentermine plus Topiramate and actually there's a combo of Phentermine and the previous two that we talked about as well and there's a lot of other ones in clinical trials that I think will be in the top five but they just haven't come yet we mentioned ambulent analogs and another one there's triple reuptake Inhibitors that are in the pipeline so um the the future of obesity medicines is very promising even better than these but Phentermine has been used for a long time it's a stimulant so some people use it again in cases kind of like ADHD or hypersomnolence or narcolepsy it gives you that like adrenergic adrenaline type feeling and also brings some of the like desire of not wanting to eat in this same class we can mention Vyvanse which does now have an indication for binge eating disorder vyvance is Dex amphetamine so just the dextro or right-handed amphetamine molecule from Adderall but in a very slow release over time it takes a long time to cleave off the lysine amino acid so that's pretty similar to phentermine the downside of Phentermine is it has risks like palpitations or even like you know if you're prone to AFib and you could have afib more often but after you've been on it for a few months especially if it's higher dose Phentermine there is a pretty significant chance of rebound quickly so you in most cases if you give someone Phentermine especially at the classically high dose and then take them off they will regain all the weight now how much of that is just because you only gave them three months to learn to learn the lifestyle interventions to like learn the diet and exercise and sleep habits that will give them Solid Ground where they're not sinking in quicksand um probably a significant amount but for that reason it's not used very often the benefit that I think we mentioned previously about Topiramate is that it can make carbonated beverages taste terrible so if you're someone that just drinks like 20 classic you know full sugar Cokes a day then that can make a huge difference putting you into a caloric deficit interesting now anything kind of a stimulant related when people come off of this do they deal with depression deal with I mean are those common side effects when people come off of these um they are with Phentermine it is usually not as significant of a withdrawal syndrome as for something like Adderall okay for vivance you have a prolonged adult withdrawal syndrome but it is not as severe because it's kind of a slower Half-Life but yes there's certainly withdrawal syndromes um but it's that way for most medications as well yeah I mean it's that way with almost anything too it's like it's that way with exercise if you get addicted to exercise and you stop doing it you'll withdrawal too so you know it's like I guess you just have to sort of substitute one addiction with another for a lack of a better way of saying it so and or most of these things like almost all we talked about as you were seeing in practice now are they're being used for what maybe somewhere for three to 12 months or people intending on staying on them for a long time uh what's what's kind of the goal A good rule of thumb is a target weight loss per month of maybe eight pounds so depending on how much and of course if if an individual has a body fat of 60 and another one has a body fat of 35 percent the 60 you would expect to faster rate loss but just for like an estimate let's say that you're losing eight pounds a month and there's 80 pounds to lose so that's around 10 to 12 months and then three to six months of monitoring after gotcha I think that's perfectly reasonable and and you know we're going to do another video which encourage you guys to watch talking about you know once weight is lost how to a keep it off how to maintain a higher metabolic rate and I think that's kind of the next Natural Evolution of this discussion so uh Kyle where can everyone find you they can find me on Instagram and a lot of other platforms at Gillette Health on Instagram it's Kyle Gillette MD as always keep it locked in here on the channel cool thank you awkward handshake