What’s Up with “Magic Pill” Weight-Loss Drugs?
What’s Up with “Magic Pill” Weight-Loss Drugs?
In the last few years, a new class of weight-loss drugs has captured the public's attention, promising significant weight reduction with minimal effort. But what are these medications and do they really live up to the hype?
Mechanisms of Action
Incretins (incretin hormones) are gut peptides that are made by K cells (endocrine cells) and are released during eating. Glucose absorption via the gut triggers the secretion of incretins - GIP and GLP-1.
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP-1) signal to the pancreas to produce insulin, hence enhancing insulin secretion and having the “incretin effect”. Therefore, drugs that increase GLP-1 were initially created for T2D.
Another mechanism of incretins is that their secretion signals fullness to the brain, hence reducing further appetite.
The downside of GLP-1 is that its half-life is only 2 minutes. Meanwhile, the saliva of the Gila monster contains exendin-4, a structural analogue of human GLP-1, but with a much longer half-life. This was the inspiration for novel innovations like Semaglutide (by Novo Nordisk), which only requires a weekly injection.
Types of Semaglutide:
Ozempic - for type II diabetes, injectable weekly
Wegovy - for weight loss, injectable weekly, higher dosage than Ozempic
Rybelsus - oral x1 daily
After a randomised controlled trial (1) has been done on 174 people, it is clear that Semaglutide results in a 15% weight loss on average over 2 years. This is BIG news.
Newer, more advanced drugs have already been developed, known as Tirzepatide (by Eli Lilly), which is a dual agonist of both, GLP-1 and GIP, meaning that two hormones instead of one are being upregulated. These drugs are branded as Zepbound for obesity and Mounjaro for diabetes, which promise a 20% weight loss on average.
Going even further, a third version of even more advanced meds are currently in Phase 2 trials. These are tri-agonists of GLP-1, GIP and Glucagon R, promising a 22% weight loss on average.
Keep in mind that there are 18 hormones that signal fullness, so advancements in this kind of drug development will be continuous in the coming years.
What are the Pros and Cons of such Drugs?
It is known that it is very difficult to lose weight for individuals that carry a lot extra of it. Lifestyle changes, like diet and movement are not helpful or may be helpful in the short term during periods of restriction, after which the weight is mostly gained back. There is a lucky minority for which diets do work and perhaps you personally know people, who turned their life around with lifestyle changes. Nonetheless, these lucky ones are unfortunately no more than 10% of the population. This is because diets generally don’t work and also because the metabolic changes in significantly overweight individuals are too profound for lifestyle changes to be effective. It is not about not having enough willpower to simply eat less and move more.
It is also known that carrying a lot of extra weight is linked to all sorts of health risks, such as significantly increased risks of metabolic diseases, like cardiovascular concerns and diabetes. Inflammation is chronically high and cancer risks are increased. These risks increase even further if there is family history of any of these diseases.
So, if overweight individuals are not metabolically able to lose weight with their own efforts and being heavily overweight may significantly decrease the quality of life and even shorten the lifespan, is it fair to say that some medication may be helpful to such people?
It is perfectly accepted in society to be taking medication for anything except for obesity. Obesity medication is stigmatised as is being overweight in general. But maybe this kind of medication is someone’s only chance to lose some weight and decrease all those health risks?
I personally am of the opinion that given that for most individuals, obesity is a hormonal disorder, there is nothing wrong with increasing those hormones artificially to produce positive health outcomes, same as for example, for someone with thyroid issues or for those with diabetes. BUT and there is a big BUT.
Potential Risks and Contra-Indications
First, of course, the risks of taking the meds need to be considered and there are plenty of them. 12 risks have been reported so far, including affected gut motility, which results in constipation or diarrhoea, intense nausea for the first few weeks, as well as increased risk of pancreatitis (although very rarely reported). It is also not recommended to take the drugs for anyone with a history or family history of thyroid cancer, as well as for pregnant women. Increased anxiety, depression and even suicidal thoughts in a few cases have been reported too.
In addition, we can’t ignore the topic of eating disorders. It is undeniable that so many people that are on these drugs are on them with an aim to shrink and starve themselves. Celebrities are a great example of this, most of which are not even overweight. This is a topic and a risk that clenches my heart, knowing how many young women and guys are doing this for these reasons.
It is important to stress that this kind of medication should NOT be taken by anyone who is not severely overweight. Otherwise, if you are of a healthy weight, you are risking all the side effects, but for what benefit if there is barely any weight to lose?
This is why it makes me so angry that Ozempic and Mounjaro are being provided so easily, accessible so widely outside of medical environments, and given out like candy to people who don’t meet the criteria, while those in need suffer from shortages.
Importance of Maintaining Muscle Mass
It is important to take into account that a significant amount of muscle mass is lost during any weight loss journey. Hence, it is necessary to combine fat loss with resistance training to maintain muscle mass. An important consideration is that muscle is heavier than fat, hence one could expect a lesser change on the scale, despite the reduction in fat mass, due to the increase in muscle mass.
Maintaining muscle mass is extremely important in older age, as otherwise it could result in sarcopenia. Sarcopenia refers to loss of muscle mass that can lead to not only being physically dependent, unable to perform daily tasks, like walking up the stairs, but also contribute to metabolic issues, like type II diabetes. This is because glucose is stored in the muscle and when there is no muscle, more glucose ends up in the blood, raising blood sugar levels.
Long-Term Risks
Unknown Unknowns
Overall, this class of drugs are new and we know very little about the long-term risks associated. The current studies only measure the effects over a 2 year or a 1.5 year period. One side argues that Ozempic has been around for diabetes for 18 years and if there was anything tragic, we’d know about it. On the other hand, so many people have never been on it and it’s never been so easily attainable for those who don’t actually need the drugs. The truth is that we don’t know what we don’t know.
Changes on the Brain
There have been remarks on such medications helping not only with appetite control, but also with reward mechanisms in general. Some have reported improvements in alcohol addiction, gambling, and compulsive shopping. It is only now that the effects these medications have on the brain are starting to surface more evidently and there is still so much that we don’t know.
Talking about changes of the brain, they can affect what makes us uniquely us. When appetite is significantly suppressed, cases have been reported where people lose interest in food experiences. This affects family meals, holidays, and relationships. This sounds like hell to me as a complete foodie. I could not imagine not being interested in trying new restaurants, new flavours, meals from different cultures. My biggest passion that is a huge part of what makes me me would be affected, but surely this is not about me so let’s get back on track.
On It Forever
What is important to know is that the weight loss promised by these drugs is only sustained for as long as the meds are taken, meaning once you’re on it, you need to be on it for the rest of your life. While this applies to cholesterol-lowering drugs, metformin or other drugs aimed at treatment, there is another risk posed. It is not yet known whether the body gets accustomed to the dosage, meaning it would have to be increased over time, potentially surfacing more unknown risks.
After all, even when on one of these drugs, one still needs to change their lifestyle and do the hard work. The magic pill won’t be magic otherwise. Partly, because as mentioned, engaging in regular resistance training is essential for muscle mass maintenance and partly, because if you’re doing this for health reasons and not for vanity, you’d want to make healthy food choices, get sufficient sleep, manage stress levels and do the hard work to aim for the best outcomes. That is not to say that one’s diet should be 100% perfect. An 80/20 framework works great, where 80% you try to make the best available choices to nourish yourself, while the other 20% is for flexibility and unplanned situations that life throws at you.
It’s Not Ok
What seems like a magic pill of a drug, it is there to treat. It is NOT a preventative measure and it will not prevent the global prevalence of obesity. In other words, it will not solve the problem at the core. It is not going to prevent people from eating ice-cream, but it can help have less ice cream and not crave more. To eat less ice-cream, the food environment needs to change.
In my view, it is alarming that there is a need for such drugs in the first place. For as long as our food environment will be filled with appetite-driving, over-palatable food, there won’t be a real change. There is a surplus of daily calories available to each one of us, yet there is hunger in the world's richest countries like the UK, where 1 in 5 people (22%) are living in poverty.(2) Multinationals like Coca-Cola and Nestle are making ethnic communities in South America and South East Asia sick and overweight. Babies are given Coca-Cola instead of water in countries like Mexico, because it’s cheaper. In schools in the US, fries count as starchy vegetables. Advertising to children remains the perfect opportunity for food companies to subconsciously influence young minds to eat more sugar and more fast food. For as long as this is the case, the population will only be getting sicker and heavier.
That is not to say that industrial food doesn’t have a place. There are different levels of processing, which are not equal. You cannot compare a ready-made soup, which is a source of a variety of vegetables, with a pack of biscuits or a chocolate bar. Moreover, a family meal at McDonald’s may be the only option for someone financially, which is a problem in itself. As long as people don’t have access to fresh produce at affordable prices or the skills to make healthy meals on a budget, for as long as the supermarket aisles, advertising to children and our entire environment will be filled with food that is engineered to manipulate our senses and make us want more, there won’t be a real change.
Change seems impossible? If you feel this way, it’s understandable. The multinationals’ influence over politics is hard to ignore. You may even know someone or are directly related to someone working in one of the multinationals. Perhaps that’s what puts food on the table in your family or in your close environment. Perhaps you feel puzzled by it all, on one hand, understanding the problem and on the other, grateful for the job and career opportunity.
Any kind of change is hard and uncomfortable. However, there is an example from the past when change seemed impossible, yet it was achieved in a relatively short period of time. I’m referring to smoking. As recently as 30 years ago, smoking was the norm. Doctors smoked, parents smoked in front of young children, everyone smoked indoors, on aeroplanes, on the metro/tube and so on. The tobacco industry seemed too big and too powerful to fight against. Yet, a generation later, everything has changed and the rates of smoking have fallen by 68% in adults (1965-2018) and youth (1991-2017).(3)
If you want to add to the change, but not sure how to - “every little helps” as Tesco says. Supply is driven by demand. You can participate towards a decreasing demand for ultra-processed foods by choosing to make cookies at home or getting your pastries from a local, artisanal bakery. Small steps have a compound effect over time.
In the meantime, it is important to be understanding towards those, who have tried everything and these medications are their only way to have a shot at a better quality, potentially longer life. Hence why there is a place for these drugs on the market, but it shouldn't be drugs or nothing. It should be drugs in the meantime, change in the food environment as the long-term goal.
Weight Stigma
Weight stigma refers to being judged based on your weight or body shape, regardless of your non-physical characteristics. Every single generation alive today has been affected by weight stigma. Starting with the “Banting diet” in 1863 and ending with today's Victoria's Secret models, Kardashian’s body ideals, social media standards and Photoshop. This has led to a worldwide weight stigma, not only in our everyday lives, but also in healthcare, scientific research, and professional settings.(4) It has contributed to the growing prevalence of eating disorders, both in females and in males with global eating disorder rates increasing from 3.4% to 7.8% between 2000 and 2018.(5) Also, the pandemic added fuel to the fire, causing an increase in prevalence (6) and worsening of symptoms of eating disorders.(7)
There is plenty of evidence to support that weight stigma in itself is a risk factor for physical health concerns, such as diabetes and heart disease, regardless of the actual body size.(8)(9)(10)(11) Moreover, weight stigma has been shown to increase the likelihood of weight gain and reduce the chances of weight loss. Also, victims of weight stigma are 60% more likely to be physically inactive (12) with the aim of avoiding being judged, compared to those who do not experience weight discrimination. This applies across all BMI categories, meaning that this doesn't only apply to people in larger bodies. Similarly, weight stigma leads to more emotional eating. Isn’t it quite ironic that weight stigma or bullying is used to encourage food restriction, but it results in even more food consumed over time? It is not that surprising, given how many people turn to food as a way to cope with stress and to seek comfort.
A South Korean study,(13) which followed over 6.7 million participants, found that those who engaged in weight cycling (yo-yo dieting) the most, had a 53% higher risk of dying from any cause and a 14% higher risk of getting a heart attack and stroke, than those whose weight was stable. This once again applies to individuals of all body shapes and sizes. This means that those in a slim body whose weight is constantly going up and down due to the dieting and bingeing cycles, are likely to be at increased risk of negative health outcomes.
If all research controlled for weight cycling and weight stigma as factors for weight increase over time, as well as poor health outcomes, perhaps the world would realise that diet culture and fatphobia are indeed largely participating factors towards causing today's obesity epidemic and increasingly poor mental health.
Final Note
Is there a place for these drugs? Yes.
Should everyone who wishes be on it? No.
I cannot stress the importance of carefully weighing potential risks of living in a significantly larger body VS the risks of the medication. This should be discussed with your doctor that knows your health history and your family’s health history.
It should be the last resort only, after everything else has been tried and tested, and possible risks weighed against the benefits. It should not be a first choice or “the easy way out”, before other methods have been tried and health risks carefully considered.
Fun Fact to End With
Do you know what the no.1 nutritional GLP-1 driver is?
Protein. Hence why it’s the most satiating macronutrient.
