hi and welcome today we're going to take a deep dive into gp1 we're going to review some statistics of diabetes and obesity insulin resistance we're going to review the natural role of gp1 in the body but also discussing our glp1 agonists which are prescription Dougs that are sweeping the nation then we're going to talk about cautions indications Contra indications that you want to consider if you are prescribing and or consuming the prescription dogs and we also going to talk about how to naturally increase your glp1 as well as tackle fat loss from an Evidence based perspective and lastly is what to do if you are taking it where your patients are how to be responsible about this and make sure you prevent any further complications my name is DrArian mismer I'm a functional medicine practitioner dror Physical Therapy register dietitian and I'm the owner of the mbin Paradigm Integrative Health Center in the Philadelphia area and I'm a medical educator for Ruba health so let's dive into some statistics so in 2021 38. 4 million Americans 11. 6% of the population had diabetes according to diabetes.
org there were some that were undiagnosed so 8. 7 million were undiagnosed and also 97. 6 million Americans aged 18 or older had pre-diabetes but let's not forget insulin resistance which can pred diabetes up to 10 to 15 years so according to the Nan's data from that same year found that 40% of us adults aged 18 to 44 are insulin resistant now let's not forget overweight and obesity so almost 70% of the population is overweight or obese so according to the the World Health Organization in 2022 one in8 people in the world were living with obesity and this has doubled since 1990 and quadrupled in adolescence in 2022 43% of adults aged 18 or older were overweight and 16% were living with obesity in addition to that 37 million children under the age of five were overweight so clearly we have an astounding issue that needs to be addressed now US Health care providers wrote more than 9 million prescriptions for wovi and other injectable drugs used for weight loss during the last 3 months of 2022 gp1 Agonist could increase anywhere between 10 million and 70 million consumers by 2028 according to Goldman Sachs and weight loss drugs could bolster the US gross domestic product by 4% in a scenario that has 30 million users and could rise to 1% with 60 million users so why is this all important as it relates to Di IES these drugs were initially approved for that so log glutide and semaglutide originally designed for glucose lowering meds in type 2 diabetes and with that the glucagon like peptide 1 receptor Agonist so the glp1 r are attractive options for type 2 diabetes because they effectively lower hemoglobin A1c and weight while having a low risk of hypoglycemia however since all of these trials have happened it has confirmed their efficacy in weight loss for for o overweight and obesity with and without diabetes hence why there has been so much speak about these drugs and their promising effects on weight l so there's five medications that are approved from the FDA for weight loss so the first one is or listat which is was in 1999 and that was to the main goal was to decrease digestion and absorption of fat the CNS drugs that are affecting the regulation of appetite were fenine and alone and then more recently is the glp1 receptor Agonist which are approved for long term which is the log glutide and semaglutide so what is the glp1 function uh naturally in the body so it's again called glucagon like peptide 1 receptor so it's an incron hormone produced by the L cells in the small intestine in response to food intake we have receptors in the brain the intestine the pancreas as well as other organs and so ultimately it is going to help regulate appetite and lower glucose it acts at the hypothalamus so it is affecting the gut brain axis via neuros stimulation to increase satiety or that sensation of fullness it stimulates mechano receptors in the intestine which can create distension so ultimately this is also going to make you feel full it acts to slow gastric motility and increase satiety again that feeling of fullness it acts on the pancreas to upregulate insulin secretion from the pancreatic beta cells so when we have pre-diabetes or we have diabetes we have decreased insulin response so this obviously can be very important in diabetes so when we look at this beautiful representation here is the role of incron in glucose homeostasis so we have the ingestion of food it is going into the GI tract we have a release of our gut hormones so we have gp1 and we have GP then we are going to have a downstream of effect so we have an influence on the pancreas we have increased glucose uptake by the muscles we also have decreased glucose production by the liver and so ultimately this is going to result in decreased blood glucose so ultimately very promising for our natural function but of course we can appreciate how it can be very helpful in a pharmaceutical drug so this is a great representation of the gut brain connection so gp1 is going to be ultimately secreted in the intestine via nutrients but then it can diffuse and bind to different neurons that are ultimately connecting to the hypothalamus so essentially we have these ascending afer information so sensory information that's going to the brain and specifically the brain stem and it is also influenced greatly by the vus Nerf because that is one of our primary connections of the gut brain so what is a gp1 Agonist so essentially a semaglutide is a glucagon like peptide 1 receptor Agonist that mimics the body's natural hormones released in the gut when we eat so it works to manage Type 2 Diabetes by doing the following it's stimulating the pancreas to produce more insulin because ultimately we have insufficient secretion of insulin in the beta cells it's stopping the liver from releasing too much sugar into the bloodstream and then it's slowing down gastric emptying so the food leaving your stomach so what are the indications for these drugs so a zic is FDI approved to help manage blood sugar in adults with typee 2 BS along with diet and exercise it can also help to lower the risk of serious cardiovascular problems in adults with type 2 diabetes and cardiovascular disease and wovi is an FDA approved drug to help with weight loss and long-term weight management along with diet and exercise in people who have a BMI of greater than 30 or have a BMI of greater than 27 but have at least one weight related health condition such as hypertension cholesterol or type 2 diabetes and it's also approved for children ages 12 or older with a BMI in the 95th percentile so considered obese so in the scale trial there was 3 3,731 patients without type 2 diabetes and a BMI of greater than or equal to 27 with dyslipidemia or hypertension and in this trial there was a significant amount of weight loss 8% compared to 2% in the placebo so then when we look at a semaglutide step trial over, 1900 patients without type 2 diabetes and a BMI of over 30 or 27 with at least one related condition also in addition to Lifestyle interventions including counseling and exercise in 68 weeks lost 14.
9% of their body weight compared to 2. 4% in the placeo group so it has shown that there's been significant Improvement in weight loss among these now let's talk about some of the contraindications so number one is multiple endocrine neoplasia so this is a clear contraindication so should be looked at as it relates to Prior history family history as well as medary thyroid cancer so if there's any thyroid involvement history of cancer this should be really really strongly evaluated and then pregnancy because there is no research on this cautions if someone has gallbladder disease if they have even just beyond that if they've had let's say fat malabsorption so if they are having stools that are greasy that are floating and aren't sinking these are signs that the gall batter should be evaluated and so even if someone had a hide to scan and it showed that there was sludge for example in the gallad these may be things that you should consider before prescribing Andor taking one of these drugs if you've had a history of Prior pancreatitis this should not be a appropriate drug so I had a patient that has had and had been dealing with pancreatitis and he has had three three different doctors recommending these drugs to him now although he's had this prior to the drugs in my opinion this should be something that should be contraindicated another caution is any kind of visual or ocular issues so retinopathy this should be something that a optomologist or optometrist should evaluate and clear ahead of time and because of the natural function of gp1 we know that it affects gastric emptying so gastroparesis as someone that has a history of gastroparesis this would also be a significant ific an caution or even if you'd like to say contraindication and also someone that is taking insulin or sanoras by themselves they don't necessarily cause hypoglycemia but you may want to consider reducing them if you taking the glp1 because it can affect it so once again needs to be monitored very closely and dosing should be started at the lowest possible dose and titrated up because although higher doses can equal higher weight loss it can also mean more effects and more serious effects so what are some more common side effects that you are you know hearing people talk about is the central nervous system effect can be decreased appetite and slower emptying so one of the biggest reasons why so many people are losing weight is because their appetite is suppressed and they're not eating as much but very common in the first weeks and then can subside as time goes on and it can be dose dependent or nausea and vomiting abdominal pain bloating constipation diarrhea early satiety so that early feeling of fullness heartburn and and also suicidal ideations so these if you are taking the drug need to be very closely monitored and you really need to understand the impact of these drugs and as professionals who are working with patients we need to really help individuals understand the depth of the wrist and the side effects and really help them make the most informed decision so what are some other side effects so pancreatitis thyroid cancer kidney failure Gall BL L disease changes in Vision hypoglycemia low blood sugar allergic reactions diabetic retinopathy macular edema blur division so all of these things are possible there is a blackbox warning on the drugs uh there are severe health problems associated with a drug and so it used to be called Black Box warning it's now called a boxed warning especially for OIC due to its potential cause of thyroid tumors or cancer and it is the most serious safety warning that's issued by the FDA and is that something to take likely so if you are taking a drug I think that there are definitely some things to to factor in um one and probably the most important is behavioral change so if we as clinicians are working with patients or for those that are prescribing really need to make sure that we're setting the patients up for Behavior change because obesity is very complex and we need to factor in a biopsychosocial model and incorporate all of the elements of the complexity of obesity in the first place so Behavior change is crucial and we'll get into that just a little bit more eating smaller meals because eating bigger meals and eating until you feel stuffed is only going to cause more gastric complications some people may benefit from taking additional B12 or even B12 injections to help with the nausea and some of the GI complaints having enough water and also with electrolytes so having enough water and then if you're just peeing all day and you're just peeing it out then that means means that you're are not really hydrated so making sure that you're consuming electrolytes is really important because with a rapid weight loss there is going to be a significant amount of detoxification that has to happen and so most people aren't prepared for that so supporting yourself with hydration is going to be very very key which hydration means water plus electrolytes and protein is one of the biggest things that we need to make sure that we are helping our patients in our community with because otherwise you are losing muscle mass very quickly which is going to significantly affect metabolic rate and strength training so this is something that can help preserve our muscle and to help potentially build muscle but not while you are losing weight so quickly but the goal would be to preserve muscle during that time period so why do we have so much weight loss essentially we're slowing down the gastric emptying so people are going to feel Fuller for longer they're going to have a decreased appetite resulting in eating less calories resulting in weight loss so also higher levels of gp1 are going to affect your hypothalamus and your brain signaling to your system that you are full so what happens with stopping the drugs so if you know someone or you've had patients that have stopped the drugs then you're well aware that the weight gain typically reoccurs fairly quickly so in a study uh one year after withdrawal of once weekly subcutaneous semaglutide to 2. 4 milligram injections and lifestyle interventions participants gain 2third of their prior weight loss with similar changes in some cardom metabolic issues so it confirms that the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health so I think this is really important because this is not always discussed as a really important variable in choosing to do the drug in the first place or knowing that you're on it and what the implications are if you have to come off of it and the other thing I think that's really important is that we want to come from a place of being able to inform our patients as much as possible this was a survey that showed in 107 survey respondents less than 10% used evidence-based guidelines to inform obesity treatment decisions so I think this is really important that we want to be looking at obesity as a whole we want to look through a functional medicine lens we want to look at the emotional mental spiritual component we want to look at the social component we want to look at what they are fueling their bodies with how they are moving their body their nervous system regulation we want to be looking at all of these aspects so that we can again help our patients in community the best what are the things that are not discussed I think this is extremely important because we know some of the obvious contraindications and indications well what are the things that are happening that we don't really care about so one is that when we are losing weight at such a rapid rate we are directly influencing our metabolism because think of the more muscle we have that is going to be more metabolically active the more fat tissue we have the more inflammatory driven we are and the less metabolically active we are so when we are losing weight at such Fast Pace we are losing so much muscle and so that is going to directly affect our metabolism and we are going to lower our non-exercise activity thermogenesis so when we are moving through our day and we are you know sitting typing you know not necessarily exercise or activity we are burning a certain amount of energy and so when we have higher amounts of neat meaning we're fidgeting throughout the day even things like shivering uh when we're kind of like moving around we are going to burn quite a bit more calories but this is going to significantly decrease as we lose more muscle when we're losing weight this fast we are detoxifying really quickly and so when we're working with patients with complex medical conditions this is actually a really big deal because it can make them feel very very ill so on top of the obvious side effects from the drugs that we already mentioned you can also experience significant issues such as feeling flu like you could feel like you have a cold you can feel greatly fatigued or have a headache all of these things can also be very very common and need to be supported properly you can have hormone suppression from nutrient deprivation we often think of malnutrition as being associated with people that are very thin but quite frankly obesity is actually one of the biggest populations that is malnourished and so when we are cutting calories even more and we're not eating properly we are also going to have significant hormone suppression so that can cause its own whole set of issues along with that are nutrient deficiencies so we need nutrients for every single reaction that happens in the body so for our biochemistry to work the way that we need to we need nutrients and so when we begin to lose weight at a rapid pace and we're also not fueling our bodies well or enough then we can also have significant deficiencies or again lowering our overall metabolic rate and as I mentioned we can lose a significant amount of muscle mass and so as a provider and also as a powerlifter my goal is to help my patients either preserve every am of muscle they have or gain ideally gain muscle and so I'm always talking about that because truly muscle is our organ of longevity which I'll speak about in just a moment and sometimes what can happen too is the longer that you take any drug you can develop things potentially wor symptoms and potentially other side effects and because there's no long-term studies at this point we do not know what the implications may be so we also want to think about how are you going to maintain this beyond the drug so if you decide to take the drug and you make an inform decision or you are helping your guide your patient to do that what is the plan to make sure that they are doing everything they can to do this in the healthiest way to support maintenance and the health benefits um also the high costs in potential supply shortages that many have experienced so far so on average it's about $1,000 per month out of pocket unless it is Ed by insurance and so in that situation what are the things that you might have to cut back on so if you are taking a drug does that mean that you're going to or your patient is going to stop going to the gym so we want to make sure that we're supporting all the areas of Health as it relates to that so one important distinction to make is that we don't necessarily want to consider weight loss fat loss so weight loss is total weight loss that also includes muscle versus fat loss where we're specifically targeting fat loss this is a very very important distinction and approach to me towards obesity and overweight so when we're thinking about types of fat we have three different types of fat so we have our white our Brown and our beige so our white is our subcutaneous adapost tissue that's our energy storage we have our Brown fat which is between the neck and the shoulder blades we have more mitochondria here and then we have our beige which is kind of mixed so it's in the white but it also can create heat so we have different storage sites in our fat cells so we have essential subcutaneous and visceral fat so essential fat is going to be necessary for a healthy functioning body our subcutanous is going to make up most of our bodily fat it's found right underneath of the skin and it's our main method of storing energy for use at a later time and then we have visceral fat so this is around the organs and the abdomen and this is very dangerous at high levels so we want to minimize this as much as possible so how do we burn fat so we have some distinct steps so number one is we have mobilization so lipolysis we're getting the fat cells from the viscera and the subcut are stored fat and we're getting them to move into the bloodstream this is going to be traveled and used as energy but then we want through the step of oxidation is to get that into the mitochondria so this ultimately is going to be converted to ATP and that happens by adrenaline and the sympathetic nervous system and then we can use this fat as energy I.
E burning fat so if we think of just an example when we are shivering when we're shivering in Sher and you're really really cold you are mobilizing that energy and then you are also oxidizing it and using it for energy so what is necessary for fat loss there are so many things and I don't want to say that this is the all extensive list but this is a pretty thorough list of all of the things that are really important number one is going to be optimizing breathing and Airway function so if you have obstructive sleep apnea Central sleep apnea upper Airway resistance where you have another Airway dysfunction that is Li limiting your ability to breathe optimally this can absolutely affect your metabolism because this is going to affect how we're getting oxygen to our tissues and ultimately our mitochondrial function sleep is one of the most important things that I always say is more important than exercise and nutrition combined so if you are not getting the amount of sleep or the quality of sleep that you need and the consistency of the sleep then this is without a doubt going to affect your metabolism nervous system regulation so depending on your mental emotional spiritual State as well as how well you are able to regulate your nervous system and be resilient to day-to-day life challenges and stressors have you experienced trauma that has not necessarily been processed and are there other psychological factors that need to be addressed shifting from ultr processed foods to Whole Foods so this doesn't mean a perfect diet it just means moving away from our highly processed and packaged foods that are filled with excess sugar ingredients and so on to do a whole food diet approach protein is one of the most important things that is necessary so we really need adequate protein not necessarily to simply survive but actually an optimal intake to thrive and especially if you are in a calorie deficit so when you're in a calorie deficit we are looking at about 1 gram per pound of body weight or at least at the minimum ideal body weight and so or or lean body mass if we have that measure so when we're looking at body composition we can begin to look at a dexa scan versus the weight on a scale we want to think about light exposure so having proper light exposure during the day 20 minutes in the morning when you first wake up to help with natural cortisol production as well as melatonin production essential fatty acids are critical so for healthy metabolism and food we want EPA of over a th000 milligrams per day that can come from things like fatty fish and we also want specific amino acids but we want to have our full amino acid profile from protein intake but specific Amino like glutamine can help with gut health and healing leaky gut for example moving right into gut health is that is 70% of our immune system it's going to have a significant effect on our metabolic Health it is going to affect our ability to regulate inflammation how we digest food so optimizing gut health is critical thyroid function and really beginning to think about you know thyroid is our Master regulator and this is when we're thinking of metabolism we want to be thinking of thyroid function but we also want to be thinking of all all of the necessary nutrients that are needed for optimal thyroid function which we rarely do we might diagnose a thyroid condition and give them a pharmaceutical but we're not necessarily looking at all of the nutrients that are needed for proper production and conversion and uh cellular sensitivity so how it's moving into the cell and so we can begin to think about these specific nutrients like iodine and selenium and vitamin D and zc strength training is super important one of the most important things that we can do to optimize our body composition improve muscle Health decrease fat which is inflammatory in nature and also we want to think about if we are truly trying to lose fat being in a calorie deficit is important if you are eating the same amount of calories but you are not eating enough protein not working out you're not necessarily going to make any changes so we want to think about that as well and sarcopenia is the involuntary loss of muscle mass strength and function as we age and so muscle mass decreases approximately 3 to 8% per decade after the age of 30 and it this rate of decline is even higher after the age of 60 so unless you are doing two things eating enough protein and strength training it is going to decline at a very rapid pace so depending on the age and your decision of you know taking one of these drugs you want to be factoring this in as again part of your informed decision or for your patients muscle is the organ of longevity so this is one of the things that is so crucial to living a long healthy resilient to life and so again I'd love to shift our thinking instead of weight loss is more fat loss because I think this is really important for our patients and if you are a consumer so what are some quick ways to improve your dlp1 naturally so there are some dietary factors there's some gut factors lifestyle factors so once again eating protein consistently there was a study that showed that eating mixed meals with a higher protein intake relative to a lower protein could be more effective in increasing natural glp1 secretion cost coffee can be very valuable but it in the studies there was upwards of six cups a day so we want to be mindful of coffee can definitely be have a positive effect in from a few different aspects but we do want to monitor the the risk reward so if coffee is helpful for you as let's say pre-exercise if it's not influencing negatively impacting your sleep we can look at all of those factors pre-biotics so this is another area where things like bananas onion garlic apples good pre iotic Foods these can be helpful as it relates to increasing natural glp1 herbate can also be something that can be used as a type of tea that you can do up to three times a day you do want to be mindful of some of the potential side effects from that so please make sure to check that out if you're considering and then there can also be other natural products like berberine tea curcumin cinnamon and so on that can also have an influence on gp1 we also want to think about lifestyle factors so these are all going to play in whether you're taking the dog or or not but sleeve deprivation can impair the body's response to gp1 making it less effective to regulating appetite and Metabolism when we look at this image of looking at the influence of the Vegas nerve when we are in a completely disregulated nervous system State and we are our nervous system specifically parasynthetic nervous system is downregulated then we are going to have effects on how we are either digesting our food our hunger hormones our sens of fullness because we're going to ultimately have poor interception or internal awareness of self so there's a direct correlation and link between our mechan receptors and chemo receptors and how they are connecting to our hypothalamus via the Scott brain axis so stress is going to directly influence this in several different ways exercise is another critical part of a healthy lifestyle healthy fat loss but Studies have reported that moderate intensity exercise and high-intensity exercise can increase glp1 levels compared to healthy and obese individuals we also want to think about gut influences so when there is disbiosis this can cause a whole host of effects so everything from increasing lipopolysaccharide which is an endotoxin which can create systemic inflammation it can contribute to if we have low diversity in the gut so we have let's say disbiosis that imbalance a bacteria and then there can be certain bacteria elevated or decreased that can also influence gp1 and specifically type 2 diabetes so what are the things that we could do to test and look at proactively so of course our normal panels of CMP CBC but we also want to be looking regularly at hemical beny and not just looking at our fasting blood glucose we want to be looking at a fasting insulin so we want to be looking at a home IR score looking at a comprehensive stool test so really understanding what's happening in the gut I think looking at the cortisol and understanding a a little bit more in depth along with tracking heart rate variability and having your patients track heart rate variability understanding their autonomic nervous system even using something like chronometer to do a detailed nutrient analysis to see what they're eating what they're not eating why they're feeling the way that they are so many of my patients when I first do a nutrient analysis they're eating so many carbohydrates they're eating such little protein and the easiest switch that I can make for them is for them to consume more protein throughout the day so 25 to 30 G of equal feedings throughout the day trying to hit their protein goal specifically moving towards 1 g of protein per pound of lean body mass and depending how active they are or if they are in Fat Loss towards upwards of 1 gram per pound of body weight and once I'm able to have them achieve that and they recognize that they are full longer and that there's a higher thermic effect of food from protein so they're burning more energy just by eating more protein when we start to see these benefits it can be so significant so whether you or you're having your patients take these drugs it is really important that we're looking in depth about all of these things helping our patients make the most informed decision so as it relates to summarizing and pulling all this together I think the biggest thing that I am hoping with all of this is that we are all more educated on the indications the contraindications the side effects the things that aren't necessarily talked about and looking at obesity and type 2 diabetes as a more more complex issue that we have to look through a functional medicine lens looking at the biopsychosocial model and really appreciating all of the aspects of genetics and epigenetics and psychology and social influences that are influencing the majority of our world right now and so I'm hoping that as clinicians that we can really help our patients no matter what the decision is is make the best decision for them and what to do if you're taking the drug if you're not taking the drug and really just make sure that you are moving no matter what towards a lifestyle of getting good sleep eating good foods moving your body and making sure that you are taking care of you because you only have one of you thank you so much for joining and if this was helpful make sure you subscribe to our YouTube channel and we will provide you with root cause medicine welcome to root the health the best place to order advantage and track results from over 30 different lab companies in one single place for free it's going to take you under 2 minutes to sign 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