Ozempic: metabolic scourge or panacea?

Ozempic and other GLP-1 receptor agonists are both controversial and incredibly popular. The popularity and controversy stems mostly from its efficacy as a weight loss drug but this is only one small part of the story. I think weight loss, as a topic is an emotional trigger for people and because of this, the logical fallacies of Internet-land begin to pop up. The utopian future where people don’t take these drugs to lose weight is far off, if at all possible and so I think it is worthwhile to offer some insight as to when and how to use these drugs,. It is also important to know that these drugs are multi-functional. They may offer people a lot of benefit when taken properly and while some people will always see it as a cop out, it is by no means a free lunch. If you take it as it is often prescribed you may be in for some real problems.

This is a fairly lengthy deep dive, a conclusion and summary is available at the end.

THE CURRENT ENVIRONMENT

It seems clear that big pharma wants you to take these drugs and they want you to take them forever, The GLP-1 market is growing at an unprecedented rate. It could be worth about 125 billion dollars in the next 10 years, Novo Nordisk, the creators of Ozempic and Wegovy have hired obesity specialists and paid them upwards of 30 million dollars a year to drive the narrative that obesity is a disease: that it is a genetic problem and needs to be treated with medication. The FDA fast tracked this drug for use in teenagers with type 2 diabetes in less than 30 days. The data as of 2021 suggests that there are over 40 000 new cases of type 2 diabetes in adolescents every year. The average scenario is that doctors are giving the drugs as a walk off prescription – You get the prescription that is for one dose per week with no follow up and no monitoring unless problems arise. The American Academy of Pediatrics recommends the use of Ozempic for obese teenagers (no diabetes diagnosis), of which there are millions. This “Academy” is heavily funded by pharmaceutical companies. Novo Nordisk is a massive advertisement buyer on many US news networks, and is the 6th highest advertisement buyers for CBS news. A 60 minutes (run by CBS) episode aired recently on the drugs efficacy for weight los and type 2 diabetes. Instead of interviewing a non partisan doctor, they used a Novo Nordisk consultant. In todays age of institutional distrust, I think we can do better in educating the public in a non biased way. We need transparency and nuance.

So that is the current economic environment from which these drugs are developing and being pushed at us. Personally, I am not of the mind to assume distrust in all institutions, authorities and capitalist endeavours. But I think it is worth being aware of the incentives driving these drugs to market. Drugs do help people, they are often life saving tools. Tools that we may need a bit too much now because our environments have developed in a way that threaten our well beings. I don’t think this is some kind of purposeful, conspiratorial design but more of a symptom of a number of issues in our culture. Health awareness is growing but the speed of change is inherently slow and so we may need to use tools like medications in order to survive the snails pace.. The best we can do is arm ourselves with information to self advocate, minimize the use of unnecessary drugs and regain control so that we are not at the mercy of big pharma for our entire lives.

HOW DOES IT WORK

I am going to be brief on how these drugs work – here is the gist of it. GLP-! agonsists are peptide signalling hormones These peptides are made internally by L-cells that line the gut and they are also secreted in the brain. These L-cells in the gut are triggered to make GLP-1 when glucose or globules of food pass in the gut. GLP-1 receptors are found in large number in the stomach and bowels (immune system), pancreas, brain and cardiovascular system. At high doses Ozempic and similar GLP-1 agonist drugs work by controlling glucose levels through a few different mechanisms, including by increasing the release of insulin, slowing stomach emptying and reducing the release of glucagon after a meal. Glucagon is a hormone that your pancreas releases in order to lower insulin and drive blood sugar higher. The slowed stomach emptying is one of the ways these drugs work as weight loss medications. You feel full quicker and longer and so your interest in food wanes. These peptides help sensitize the body to insulin and then helps secrete the insulin when needed – this is how it helps people recover from type 2 diabetes. There is some preliminary evidence that if given early enough, semaglutide or other GLP-1 antagonists might be able to heal pancreatic function in type 1 diabetics and eliminate the need for insulin. This study was very small and the drug was only given to young participants with a new diagnosis id T1D.

There is also an effect on your hypothalamus which controls cravings, hunger and satiety and there appears to be a psychological shift away from obsessive thinking about food and sometimes alcohol as well. The hypothalamus is an autonomic nervous system and hormone regulating gland and so it makes sense that mood and ‘reflexive’ or addictive patterns may be altered if certain neurons are stimulated. A recent study pinpointed GLP-1 receptors in the dorsomedial hypothalamus as potential sources for pre-meal satiation in both mice and humans. Figuring out how these compounds can inhibit cravings or excessive eating at the brain level is going to be the key to understanding how to use these drugs effectively at a much lower dose (more on this later). The current dosing levels are problematic, not because of the most commonly mentioned side effects of nausea, mood changes and vomiting but because of the hidden metabolic collapse that can happen behind the life-long dependence of the drug

PHYSICAL SIDE EFFECTS

The official list of commonly occurring side effects for Ozempic are nausea, vomiting, abdominal pain, constipation and diarrhea. They can range from non existent to moderate and occasionally severe. But if you scroll down on their website you will see that there is a longer list of more serious side effects, and the frequency at which they occur is unclear. These include; thyroid cancer, kidney failure, pancreatitis, changes in vision, hypoglycaemia, gall bladder problems, bowel obstruction and severe allergic reaction. I’ll go through what I have found on some of these –

I have not seen any human studies linking Ozempic to thyroid cancer but there are some rodent studies that do show a correlation. The GLP-1 receptor systems vary quite a bit between rodents and humans and so the current interpretation of the data is that the risk for thyroid cancers would be quite low in humans. That said, the longitudinal studies in humans have not been done and so even though the general consensus is that the benefits outweigh the risks, I would be hesitant to take these drugs at the usual doses if I had a history of thyroid disease.

No long term studies have been done to show high dose semaglutide effects on people with kidney disease but up until recently it has not been recommended that anyone with a history of kidney disease take these drugs. Curiously, a recent study called the FLOW tria showed that a 1mg weekly dose of semaglutide reduced the progression of kidney disease and kidney and cardiovascular death by 24%. The average follow up was 3.4 years and they ended up cutting the trial short in order to give the control group the medication. This study was funded by Novo Nordisk and so there is a conflict of interest but that doesn’t necessarily discount the findings. They just need to be replicated. I would think that most medical practitioners using these medications, even at a low dose would be getting regular blood and urine analyses done to be mindful of kidney issues.

Pancreatitis affects digestion and if it gets bad enough, it can kill you. I have seen statements that Ozempic can increase the risk of pancreatitis by 900%. I am not sure where this data came from but the few studies I have read have found no significant correlation. If you have had a history of pancreatic or gallbladder issues, these medications may cause some problems. Unfortunately, our medical system is not great at pinpointing low level disorders with these organs. If you haven’t had obvious symptoms of either, then you might not know that you are at risk. A thorough system evaluation may be prudent before going on one of these medications. Once again, when taking any medication at high dose I think it is imperative to have regular blood panels done to see how everything is going. The simple solution to the risk may be to find a way to get a lower dose of the peptide without using a prescription of Ozempic or Wegovy.

Most medications do limit nutrient uptake and so you never know what kind of deficiencies, inflammation and disorders you can be developing. In one study, semaglutide injections were correlated with a decrease in serum albunin, B12 and zinc. These deficiencies may simply be due to a sudden drop in protein levels and so It is imperative that you follow a guided nutrition plan along with these medications. Some studies are coming out showing the relationship of semaglutide with lifestyle changes. The unfortunate conclusions are that nutritional programs and exercise don’t embellish the weight loss benefits of semaglutide at the normal doses of 2.4mg/week. This is missing the point of what proper nutrition and exercise do which is to maintain proper macro and micro-nutrient levels, feed our organs and systems as well as regulate metabolism and endocrine function. A more nuanced conclusion may be that at such a high dose, semaglutide interupts the long term health adaptations that proper nutrients and exercise can have, producing a metabolic drain. The high dose overrides the possible effects nutrition and exercise may have on weight loss but weight loss is not (or should not be) the only goal here. If you simply reduce calories but do not feed the system then you still have non nutritive foods taxing the system, just at a slower rate.

Bowel obstruction can also be a big problem. One of the reasons semaglutide works for weight loss is that it slows gastric emptying. But this slowing can be too extreme and cause paralysis (gastroperisis) and obstruction. Some small studies have shown that this goes away after coming off of the drug but there are ongoing lawsuits where claims have been made that paralysis continued even off of the medication. I have seen statistics that say 1 in 20 people can experience gastroperisis while on Ozempic but I am not sure if this includes low level gastric emptying or only extreme slowing/paralysis and obstruction. Gastroperisis can cause nausea, vomiting and even death. In some cases surgery may be needed to empty your gut. Anecdotal evidence from Functional medicine practitioners I have heard discussing their protocols suggest that at micro-doses, paralysis does not happen.

PSYCHOLOGICAL SIDE EFFECTS

Some of the side effects of semaglutide are psychological and include depression, anxiety and anhedonia – or the lack of interest in previously enjoyed activities. Wegovy, a drug made by the same company as Ozempic and using the same active compound of semaglutide, explicitly states the risk of anxiety, depression and suicidal ideation with its use for weight loss. The dose is higher than that of Ozempic which is only approved for use in type 2 diabetes but is often used off label for weight loss. Ozempic does not site the same psychological side effects for its drug but hundreds of public reports on FAERS website (FDA adverse event reporting system) suggest there might be a similar issue. The claims on FAERS have not been verified and so we can only make assumptions at this point. Its quite possible that there are thousands more people suffering from mental issues as side effects due to the medications and not reporting it. We know that the higher doses of Wegavy are often problematic and so it only makes sesne that the slightly lower doses of Ozempic may be causing harm as well.

The discussion on depression and anxiety is troubling but lacking nuance, especially throughout the major media outlets . I think it is important to consider that the dose may be the poison here. We also may want to consider that many of the people taking these drugs are coming from a place of desperation where they have been using food to self medicate underlying depression and anxiety for years. What happens when you suddenly take away a crutch without dealing with the underlying issue? When there is a drastic change in how you think and behave – which these drugs do – there will be a sudden shift in identity and this can be deeply unsettling. GLP-1 agonists, at low dose may offer a window in time where the obsessive thinking and addictive behaviours can subside and make room for new ways of thinking and doing. It is possible that similar to psychedelic treatments for depression and PTSD, semaglutide may allow for new neuronal connections to be made and if paired with constructive lifestyle changes, may be a portal out of the fog. But high doses seem to be overwhelming for some people – just like a mind blowing DMT trip to infinity might be overkill for someone trying to overcome some anxiety!

Adipose tissue is considered to be part of our endocrine system. Fat cells produce hormones like leptin, resistin, adiponectin and cortisol. They store and release estrogen, metabolize testosterone and play roles in producing cytokines. While reducing adipose tissue is considered a healthy way to balance hormones and lower general inflammation doing so at a rapid rate can create possible negative outcomes, even if temporary. Semaglutide could be a potent tool for regulating endocrine health if done so at a moderate pace and monitored with regular hormone panels. But with the willy-nilly high dose frenzy that the pharmaceutical companies have normalized it is very possible that the sudden shift in hormone levels could be one of the factors triggering mental strain on patients.

Another possible factor in the increases of depression and anxiety is that with the rapid weight loss there is a sudden unloading of toxins into our blood stream. fat cells are storage containers for a lot of junk that your body doesn’t want but can’t clear away. If you suddenly empty the contents by shrinking the cells, then large amounts of that trash gets released back into your body before being processed out. If you are doing this at a time when your liver and/or kidneys are not functioning well, then you may feel pretty lousy for a while. Guess what might reduce this? Lower doses alongside a nutrient dense eating plan that supports liver and kidney function. This means plenty of polyunsaturated fats, lean proteins, phytonutrients and fibre! Putting this all together while under a severe caloric restriction is quite difficult which is another reason we should rethink the dosing strategy.

MUSCLE LOSS

When GLP-1 agonists are taken at the current dosing the basic outcome is caloric restriction. You no longer feel the want or need for big or even normal sized meals and when you do eat, you feel full faster and for longer. The calorie intake people maintain on these drugs varies widely depending on dose and diet. But many people have a hard time eating more than 800 -1000 calories a day. This is very low, especially if you are attempting to change your lifestyle to include more exercise. At this level of calorie restriction we see rising levels of cortisol and reduced level of thyroid hormone triiodothyronine (T3). This hypothyroidic effect is part of a metabolic shift downwards. The theory is that the body is trying to reserve some energy as the system is suffering from inadequate calories for homeostasis. Your body is losing trust in the environment providing nutrients. In order to regain this trust, it will take a lot of time and consistent patterns. We see this in yo-yo dieters – a perfect example was in contestants on the show The Biggest Loser. The massive and sudden caloric restriction paired with very bad training advice was a disaster for those people.

The potential metabolic issues continue with the loss of muscle mass. On regular doses, we are seeing massive levels of weight loss but up to 50% of this is in muscle. A study in the New England Journal of Medicine followed 1961 overweight non-diabetics for 68 weeks with weekly doses of 2.4g of semaglutide (Ozempic). The mean drop in body weight after 68 weeks was 14.9% which is significant! But what is not highlighted is that almost half of that is lean body mass This study was supported by money from Novo Nordisk and so we need to take the media driven results with a grain of salt.

Our muscles are part of the glucose control system. For a long healthy life we need to prioritize our muscle mass and preserve our metabolism. At the current regular doses, these drugs are outstanding at reversing short term cardiovascular risk but do not necessarily set people up for long term health. They set them up for being weak, metabolically susceptible and dependent on the drugs.

The good news is that the perfect storm of metabolic downshifting is preventable. A low dose of a GLP-1 agonist medication will help you get back on track by regulating your blood glucose and insulin levels. They will moderate your cravings and obsessive thinking about food and alcohol and may even clear cognitive dysfunction and immune issues by lowering inflammation in the gut and brain. As long as you are prioritizing protein intake and doing at least 3 moderate to intense strength training sessions per week, you should be able to maintain if not gain muscle mass. One study has shown a potential increase in muscle vascularity while using semaglutide. If this is indeed true, then people who focus on resistance training and protein intake may see improved results from exercise compared to those not taking the medication. I believe this would most likely be true for people who are new to training and less so for those of us who are exercise adapted.

INFLAMMATION & IMMUNE SYSTEM

GLP-1 receptors are found on certain immune cells including neutrophils and eosinophils. Activating these cells has modulatory function on inflammation and immune response. Semaglutide has been shown to activate these cells as well as endothelial cells and reduce activity of inflammatory cytokine cells in mice. A recent study showed that semaglutide inhibited inflammatory processes in epicardial fat during heart surgery which may lead to added benefits to heart health, post procedure. The immune modulating mechanisms of GLP-1 is still not fully understood but the possibility of using varying doses to work in tandem with cancer therapies and cardiac surgeries is very interesting. These medications may also be helpful in treating people with food allergies and other autoimmune diseases where GLP-1 deficiencies may play a role.

NUTRITION

It may be that the dieting crazes of high carbohydrate, low protein and ow fats have created GLP-1 deficiencies in out bodies. The tendency of people to yo-yo diet their way through weight management can find themselves with endocrine issues and metabolic disease. Pre- metabolic disorder may indeed involve some sort of GLP-1 inhibition. When minor, It is possible to fix some of these problems with nutrition.

GLP-1 is released whenever you eat but some foods increase it more than others. Fibre rich foods like almonds, artichokes, beans and pumpkin seeds help slow down digestion. This allows for a sustained GLP-1 release time. Protein has a significant impact on GLP-1 release. An intake of 30-40g per meal can increase the bodies release of this hormone and naturally balance gut-brain health and initiate muscle synthesis. Bitter foods like coffee, sencha green tea, arugula and dark chocolate activate receptors in the lining of your gut that signal GLP-1 to be released. Foods high in polyphenols trigger receptors in your gut as well as feed the healthy bacteria in your intestines both of which help the release of GLP-1, None of these will act as powerfully as even a small dose of semaglutide and so if you are in dire need for a change – be it because of type 2 diabetes or severe obesity and metabolic issues – then it may be best to get a prescription. But the very best way to stay healthy is to find a way to naturally maintain homeostasis. So start including foods from the above list and make sure to prioritize protein while adding resistance training to your routine.

PSYCHOLOGICAL BENEFITS

Given that we find receptors for this peptide all over the body, this may explain why medications like semaglutide seem to have widely beneficial effects on things like cardiovascular health, cognition and immune diseases. Trials are underway to study the possibility in reducing neurodegenerative diseases like Alzheimers as well as severe immune dysfunction. I have heard case studies of significantly improved cognitive functioning as well as a reversal of Crohns disease and severe psoriasis. This was done with a cycling of a very small dose. One study has shown a drop in blood levels of C-reactive protein (an inflammatory marker) with a minimal weekly dose of 2.4mg. Another study on mice suggests that the mechanism responsible for lowering inflammation in the brain and body resides in semaglutides effect on the SIRT1 pathway. This is yet to be seen in humans but is very intriguing.

ESCAPE PLAN

If you’re gonna go in, go in with an escape plan. The pharmaceutical companies have labelled these drugs for permanent use If you have been taking them at the normalized doses and want to come off of it but have not adjusted your lifestyle then you will most likely have a metabolic crash and begin to gain the weight back. But this can be avoided. There are a handful of functional medicine practitioners that recognize the issue with the dose and can use the peptide itself off label as a way to adjust to a micro-dose. Cycling on and off of the micro-dose with close monitoring can allow people to know when their lifestyle changes have adjusted alongside the hormonal balancing of the drug. If symptoms persist, or blood labs suggest an issue remains, then you can cycle back on the drug and try again later. This is the only way I would ever advise one of my clients to take semaglutide or an equivalent drug. Clearly there are many benefits of taking this drug and the ongoing studies suggest that the list may continue to grow but I think the rush to inflate profits and create dependence has overshadowed the potential.

Prevention and healing is not commonly found in the current medical system. You need to find a functional medicine practitioner or advocate for yourself with a doctor that is open to reason. I know some people who have built their own team of doctors that they trust and have had them communicate with each other in order to solve chronic health problems that previously were not treated properly. This takes a lot of work on your part so my best advice is to seek counsel with a naturopathic doctor and a nutritionist. They will be good sources of information and most likely to look at things holistically. From there you can get bloodwork done and begin to gather data and make a plan.

A NOTE ON CHEMICALS

Lets not forget that GLP-1 is something that is made by our own bodies. Semaglutide is altered by adding alanine and lysine (both are amino acids) and a carboxyl group which is a main component of amino acids and fatty acids. The carboxyl group allows for the protein chain to last longer in the body. Yes, this is chemically altered, which makes it man made, but it is made up of fully natural compounds that are found in our bodies or taken in as foods. The proteins in this medicine are not toxic but like anything else that we could possibly consume, including water, it is made up of chemical compounds and the dose is the poison. I sit amongst you who are medication hesitant. I do not like the culture of treating symptoms rather than healing the root cause of an issue and above all I prefer preventative measures. But no matter the measure, it will be by using chemicals. Defining things properly can eliminate some of the fear and I do think it is important in the current age of distrust to make science literacy a goal for the next generation. Industry will dose things to create chronic need, we have seen this again and again, but if you know what the thing is, you can stop fearing it in itself but remain weary of the method by which it is used. I think this is a helpful way to navigate the medical system with less anxiety and anger.

CONCLUSION

I am not a doctor and so I can not give anything but an educated opinion on whether Ozempic or other GLP-1 agonists are a good choice.

Each individuals situation needs to be taken into consideration. The systemic health concerns of one person will almost never match that of another and the psychological complexities with food make decisions around these drugs more nuanced than what the mass media tends to allow for. These medications have been used successfully in treating type 2 diabetes for quite some time and I think we need to recognize this as a win. I am hesitant to assume that people who are on these drugs are also following strict, organized lifestyle changes as well in order to remove these drugs as quickly as possible. But I definitely understand the urgency for some who need help with their disease. This urgency can also exist for people who do not yet have a diagnosis of diabetes but are obese and are on the path of serious cardiovascular risk and metabolic decline. Lets be clear, you can be overweight and still have no signs of being unhealthy – at least with the rudimentary health markers most doctors use. But when the fat around your organs starts to build up, you are on course for very serious health issues. The common concern is that these drugs offer a free lunch for people who are technically suffering from preventable problems. That with an option of a weekly injection, people can get away with maintaining bad habits without putting in any effort to change…and at the cost of everyone else (for those of us who have health care).

No doubt this is going to be the path for some and others will straight up abuse the drug for reasons of vanity, as we have already seen in hollywood. But having worked in health and fitness for as long as I have, I can assure you that it is not always as simple as you think it is. It can take decades for people to manage it themselves and in the meantime, they may be laying down plaque in their arteries and building up anxiety and self loathing. Why shouldn’t we offer people a window to an easier path? Especially if it is done in a way that actually allows them to thrive? Just because you or I think its a cop out and it wasn’t the way we did it? Let it go and be there for the person so that they can build themselves back up I assure you, if they do it in a healthy way, it is not going to be that easy.

The risks are high for people who are given the full dose of these drugs. And the drugs on their own will not make you super healthy, but they will turn things around and pull you from the edge of serious disease. I implore you to find a way to micro-dose it if you can. And if you can’t then I urge you to work with a nutritionist and fitness coach who can help you maximize the benefits and minimize the metabolic costs of these drugs. Try to make your time on these medications as brief as possible.

SUMMARY

• Ozempic has a lot of money and influence behind it do drive a narrative that obesity and type 2 diabetes require medication to treat it.
• Ozempic and Wegovy both use semaglutide as the main active compound. Wegovy has been used to treat type 2 diabetes for years while Ozempic has been marketed solely for weight loss. Both drugs use an increasing dose size, prescribed for life.
• GLP-1 is a peptide signalling hormone that naturally occurs in the body. Semaglutide is a compound made up of the same peptides (slightly altered) with a carboxyl group added to it so that it lasts longer when absorbed.
• Semaglutide works by slowing food emptying in the gut as well as by controlling blood glucose and insulin levels. Given early enough, it appears that semaglutide may heal the pancreas enough to stop the need for insulin shots for type 1 diabetics.
• GLP-1 receptors exist in the brain as well as throughout the gut/immune system and pancreas.
• Common side effects include nausea, vomiting, diarrhea, and stomach pain.
• Less common (but unverified) side effects include, pancreatitis, kidney failure, thyroid cancer, gastric paralysis, major allergic reactions, changes in vision and bowel issues, depression, anxiety and anhedonia.
• More studies, not funded by Novo Nordisk are needed to verify if these more serious side effects are actually probable and if they are reversible.
• Preliminary research suggests that many of these side effects are due to the high dose used in all prescriptions.
• Anecdotal evidence from functional medicine practitioners using the peptide off label show that many of the serious (and some of the less serious) side effecst are non issues at micro-dose level but that weight loss and hormone balancing will be slower.
• Muscle loss and metabolic slowing is another serious reaction from these drugs. Muscle loss has been shown to be severe when when using these drugs. This is akin to any major caloric restrictive regimen. This can be combatted by prioritizing protein and adding strength training to your exercise practice. But doing so in any dramatic way is taxing on the body when caloric restriction is high. So low dosing would be much healthier.
• Other benefits found from using GLP-1 agonists include, cognitive improvements, immune system regulation, reduced risk of colorectal cancer, lowered inflammation, reduction of cardiovascular risk and selective hormonal balancing. Some of these potential benefits will not be seen at high doses while others are only seen at high doses.
• Strict adherence to lifestyle changes along with a smaller dose may mitigate some of the psychological side effects seen with these drugs.
• There is no nuance in the dosing for these drugs and very little focus on using them in tandem with lifestyle changes that will actually make you healthy rather than mask the root cause. Semaglutide will still do a wonderful job at regulating glucose and insulin for those in desperate need,. It will also help those people who are in urgent need of some help curbing cravings and the mental overload that comes with addictive patterns. These drugs are effective and efficient but they come with some serious problems. I would recommend a systemic overview to look for potential counter-indications before taking them at the recommended doses. I would also implore people to seek counsel of more holistic medical practitioners who may advise you on the healthiest way to use these drugs.

For any of you looking for nutritional programs to run alongside a current prescription of GLP-1 agonist medication or any other chronic metabolic disease medication fell free to contact me to set up a one on one evaluation. You do not need to be in the Montreal area, we can set it up online.