Mounjaro – The Miracle Weight Loss Drug?

April 13, 2025 | By: Joseph Hearnshaw

Let’s Talk About Obesity & Overweight

Obesity is an ever growing issue, with 64% of adults over 18 years of age in England estimated to be overweight or Obese between 2022-2023 [1]. Obesity is highest in those living in areas of the most deprived areas at 71.5% overweight and 35.9% obesity, versus 59.6% and 20.5% in the least deprived areas, respectively [1]. We’ve known about the condition since ancient times, where Hippocrates notes that obesity is not merely a disease, but also a precursor to other health conditions. In essence, Obesity, as defined by the World Health Organization, is simply characterised by the abnormal or excessive accumulation of fat which poses a health risk [2]. The level at which this threshold is met varies by definition, but simply put it’s a problem when it begins affecting your health – which isn’t always symptomatic (at first). A good example is with certain complications, such as hypertension, which is often a comorbidity, and can have devastating long term consequences [3]. The complications of which are multi-found and include [2], [3], [4], [5]:

→ Hypertension (High Blood Pressure): Can lead to greater risk of developing other cardiovascular diseases.

→ Coronary Artery Disease (CAD): This is the accumulation of fatty plaque in the blood vessels that supply blood to the heart, which can cause arterial narrowing and ultimately a heart attack.

→ Heart Failure: That is, a reduction in the ejection fraction of the heart, which is how much blood the left ventricle pumps out with each contraction. In summary, the heart can’t pump as much blood.

→ Atrial Fibrillation: Commonly associated with the development of heart failure and thromboembolism, and can lead to strokes and infarctions. There’s a 5% increase in the risk of developing atrial fibrillation with each unit increase in BMI.

→ Stroke: A stroke is when blood flow to the brain stops and with obesity and overweight there is an increased risk of early-onset ischemic stroke.

→ Venous Thromboembolism: Obesity and overweight can significantly increase the risk of deep vein thrombosis and pulmonary embolism, which is where a blood clot forms in the veins.

→ Obstructive Sleep Apnea (OSA): This is where there is complete airway obstruction during sleep, which has systematic negative effects on your health including negative cardiovascular and metabolic effects. It can lead to insulin resistance, hypertension, CAD, and hypogonadism, all of which provides a great environment to increase fat accumulation, leading to even worse OSA.

→ Obesity Hypoventilation Syndrome: This is a condition in which severely overweight people fail to breath rapidly or deeply enough, leading to lower oxygen levels and high carbon dioxide blood levels. This puts strain on the heart, which can lead to heart failure and leg swelling.

→ Type 2 Diabetes: Around 80% of patients with Type 2 Diabetes are obese. This is insulin resistance leading to a host of issues such as heart disease, kidney disease, and risk of stroke, if not managed.

→ Dyslipidemia: Around 70% of patients with obesity have this, which is clinically elevated low-density lipoproteins (LPL) and reduced levels of high-density lipoproteins (HDL), which leads to the increased risk of atherosclerosis (plaque buildup in arteries which increases the risk of blood clots).

→ Metabolic Syndrome: Clustering of at least 3 of the following five medical conditions: abdominal obesity, hypertension, high blood sugar, high serum triglycerides, and low HDL. It can lead to T2DM, cardiovascular disease, stroke, kidney disease, and nonalcoholic fatty liver disease.

→ Idiopathic Intracranial Hypertension: Raised intracranial pressure (increased pressure around the brain) which manifests itself as severe headaches and other symptoms such as ringing in ears, vision loss, and shoulder pain. Idiopathic intracranial hypertension disproportionately affects those with obesity, with 90% of cases occurring in those overweight or obese.

→ Osteoarthritis: Increased weight on the joints causes a greater compressive force to be applied and altered biomechanics. This can lead to inflammation around the joints, which leads to pain and thus a sedentary lifestyle which contributes to further weight gain.

→ Non-Alcoholic Fatty Liver Disease (NAFLD): Currently one of the leading causes of chronic liver disease in the UK, affecting around 30% of the population. This can progress to liver failure and/or cancer

→ Gallstones: Solid deposits which form in the gallbladder, usually made of cholesterol. If they become trapped in the opening inside the gallbladder, they can cause intense pain. It can develop into inflammation of the gallbladder.

→ Gastroesophageal Reflux Disease (GERD): Acid reflux, where stomach acid repeatedly flows back up into the tube which connects the mouth and the stomach (esophageal). It can cause tooth erosion, sore throats, and increase the risk of developing barrett’s esophagus which is a precursor condition for esophageal cancer.

→ Chronic Kidney Disease: As the name suggests, this can progress if unchecked and lead to kidney failure.

→ Hypogonadism: Due to role of adipose tissue in the reproductive system, low sex-steroid hormones can occur, which has a host of other issues you can read all about here.

→ Polycystic Ovary Syndrome (PCOS) in Women: Characterised by irregular periods, excess hair growth, and sometimes cysts on the ovaries.

→ Depression & Dementia

→ Delayed Wound Healing & Reduced Skin Hydration

→ Increased Risk of Infections: From skin infections, to respiratory, the risk increases greatly due to impaired immune system functioning, impaired skin health, and so on.

→ Neoplasm: Increased risk of cancers, particularly Esophageal adenocarcinoma, Gastric cancer, Colorectal cancer, hepatocellular carcinoma, cholangiocarcinoma, pancreatic cancer, endometrial carcinoma, ovarian cancer, breast cancer, renal cell carcinoma, and multiple myeloma

All the above has significant repercussions to wider society in the way of health and economic costs. The world obesity atlas 2023 predicts a global economic impact of obesity and overweight to be $4.32 trillion a year by 2035 [6]. Bottomline, Obesity and Overweight are not good for us. Conversely, being below a healthy weight is also incredibly problematic. As with most things, balance is key. But what is the threshold for overweight and obesity?

Typically, Body Mass Index (calculate it here) is used to classify it, and StatPearls suggests the following [7]:

Severely Underweight Individuals: BMI <16.5 kg/m²
Underweight Individuals: BMI <18.5 kg/m²
Individuals With Normal Weight: BMI ≥18.5 to 24.9 kg/m²
Individuals Who Are Overweight: BMI ≥25 to 29.9 kg/m²
Obesity: BMI ≥30 kg/m²
- Obesity class I: BMI 30 to 34.9 kg/m²
- Obesity class II: BMI 35 to 39.9 kg/m²
- Obesity class III: BMI ≥40 kg/m² (also referred to as severe, extreme, or massive obesity)
Asian and South Asian populations
- Individuals who are overweight: BMI between 23 and 24.9 kg/m²
- Obesity: BMI >25 kg/m²

However, body fat percentage is a better predictor of visceral fat mass and healthy body composition, with overweight typically being defined as 25% and 36% for men and women respectively, and obesity at 30% and 42% for men and women, respectively [8].

All of this begs the question of how does one become overweight or obese in the first place? It’s multifactorial, with non-modifiable factors such as genetics, and modifiable factors such as epigenetics, physical inactivity, and excessive caloric intake. Even the intrauterine environment plays a role (being obese in pregnancy can lead to an increased risk of obesity in childhood). The postnatal environment is also crucial, and sleep deprivation in babies can lead to weight gain, likewise sleep deficiency can lead to the same in adults. Various drugs increase the risk too, such as certain antidepressants, antipsychotics, antidiabetics, corticosteroids, and other drugs [9].

Other factors include socioeconomic status, which varies country to country and is complex and behaviourally driven, ethnicity which carries a genetic component. Another factor is psychosocial components, with stress being a contributor to adiposity alterations due to chronic exposure to glucocorticoids and emotional/comfort eating behaviours. Endocrine disruptive chemicals may also be a contributor, such as phyto-oestrogens and BPA in plastic. The microbiome is very important too, which is influenced from the point of birth (C-section vs vaginal birth) onwards [9].

Let’s Get Real About Weight

Firstly, it’s important to make sure that you are only losing weight if it is necessary to do so. If you fit the category of overweight or obese, or approaching that, then it’s time to start thinking about weight management. Adipose tissue (fat) serves an incredibly important function to our overall health and wellbeing; we need enough of it [10]. The problem is when there’s too much of it. Overweight and obesity is a multifactorial and complex issue. It’s important that we don’t solely point the finger at one thing alone. But, where we need to make changes, we must focus on modifiable factors. We can’t easily modify our socioeconomic status, we can’t control many things that happen in our life which contribute to stress too.

But, we can work on trying to manage stress with tools such as mindfulness and meditation, the sauna (if healthy and able), exercise (if able), and diet. All of which has a circular relationship; an improved diet helps with weight loss and improved gut health. With that, better metabolic health and increased resilience to stress. With less weight, your ability to do physical activity increases, and as such you expend more calories, reducing weight further. It also builds your stress resilience up further. Ultimately, for most people, we can control weight with caloric intake and ensuring we trend towards a negative energy balance. That is, we ‘burn’ more than we ‘use’. That can be achieved with both diet and exercise. But this is a simplistic take on the topic and does not acknowledge the nuances of real life.

A Personal Note on the Struggle with Weight

To the reader, know that I know some of your struggles, and I sympathise with those I have not experienced too. It isn’t easy. I’ve been there, by the way. I’ve yo-yoed back and forth, from dealing with body dysmorphia to stress, to all kinds of other factors involved. Appetite dysregulation secondary to stress from the demands of intense work is my current issue, with the only semi-solution being a high fibre intake (as much as I crave more!), coffee, and sheer will power. But I have to be kind to myself too and acknowledge that if I do fail, it’s okay. We can’t always be at 100%, but I do have to get back up and continue striving for a healthier me.

You too may have struggled with weight for one reason or another. You may work in a difficult place with difficult people, and difficult situations. You may be stressed. You may struggle to get by. Kids, caring responsibilities, relationships, work, and so much more. Much of which are age-old human problems, some of which are modern problems; exposure to fast-food convenience food when you can’t cook because you have to work late to make ends meet with a cost-of-living crisis, with minimal support, and young mouths to feed. Or a disabled family member that needs caring, or a boss that is ever-demanding and forces you to work long hours. Fear of missing out with friends and family at a restaurant, which is a very socially important aspect of modern day lives! All these things and more lead to increased stress, reduced time to focus on oneself, and worsened eating behaviours. This leads to a negative feedback loop of worse eating behaviours, even more inactivity, and more stress, with reduced stress tolerance.

If you’ve ever been on a plane, you’ll know the first thing you’re told is to put a mask on yourself if it ever comes out, then help your fellow passenger or child. The same is true now – within reason, you need to look after yourself to help others, and there is always someone who cares about you (no matter what you think). But you need to care for yourself to be the best you and this is what loving yourself truly means – taking time aside to take care of yourself; you are amazing! So stop and take a pause: just one minute. Ask yourself, what am I not doing that I could be doing?

If you feel stressed about excess weight, don’t worry – it can be lost. Small modifiable changes in behaviour that lead to better diet and activity (where possible) will help us get one step closer. The most important thing you can do today is to educate yourself on nutrition and physical activity. I could write a whole article on this but that’s for another day.

We could write all day too about optimal diet strategies to lose weight and then maintain it, but it is a very long topic. The bottomline does hold weight when we weigh up the pros and cons, eating less than you need to stay the same weight, if overweight or obese, is vital. Portion control and restrict your sizes if counting calories is too difficult. Cut the takeaways. Go for walks (if you can) with the kids or your partner, or just yourself and some music. Enjoy the environment around you. It’s the first step towards improvement. The NHS has a fantastic resource to help with educating yourself on better eating habits.

Mounjaro, How Does it Fit Into All of This?

I want to touch on one particular modifiable factor: Caloric intake. If you eat less such that you have a net negative energy balance, provided you don’t have a rare adipose disorder, and are not on certain drugs, you will ultimately lose adipose tissue. The composition of the macronutrients (protein, carbohydrates, and fats) determines to some extent where the loss comes from, with a higher protein calorie-restricted diet trending towards less muscle loss (important for good musculoskeletal health), and how easy it is to stick to it [11]. Balance is always important for health, though. We often don’t get enough fibre, vegetables, fruits, water, and healthy fats in our diets. Even bodybuilders in my experience often don’t, as they’re too focused on protein and carbohydrate intake.

One of the biggest issues in the western world is, in my view, appetite dysregulation. Not in the form of an ‘eating problem’, what I mean is simply the feeling of needing to eat and being hungry. It’s a system governed by a complex feedback loop: the neuroendocrine system, beautifully illustrated by this diagram [12]:

In overweight and obesity, this system can be totally dysregulated and lead to the feeling of not being satiated after eating, leading to eating sooner, or eating specific comfort foods. Albeit, more complex than this, these pathways are important to hunger regulation. Notably, Ghrelin is primarily responsible for the feeling of hunger. It’s also a very important hormone as it plays a role in heart and musculoskeletal health [13]. We can become resistant to certain satiety hormone pathways like that of Leptin [14].

You will note GLP-1 in the figure, which is a satiety hormone (makes you feel full). Well, drugs like semaglutide and dulaglutide specifically target the GLP-1 receptor (what GLP-1 binds to, to give that feeling of fullness, among other things) [15]. The discovery of GLP-1 isn’t new; since the early 1980s we’ve known about it [16]. The history of it is quite interesting, with the first FDA approved diabetes drug based on it, exenatide, being developed in 2005. GLP-1 is a peptide hormone that’s synthesized in the pancreas, and it is an endocrine hormone. It is secreted in response to nutrient ingestion (eating) and neuroendocrine stimulation. It helps control blood glucose levels and the action is quite ephemeral, lasting only 1-2 minutes within the circulatory system under normal conditions. The effects of which are well demonstrated by the below figure [17]:

GLP-1 can regulate appetite significantly, and GLP-1 mimics like liraglutide, have significant weight loss effects on obese and overweight patients without diabetes. It works quite remarkably well. It achieves this by delaying gastric emptying, increased satiety, and increasing resting energy expenditure and directly influencing the appetite centre of the brain [17].

Tirzepatide, aka Mounjaro, is a dual agonist. It targets both the GLP-1 receptor and GIP. GIP is another insulin secretion agonist, and it helps release insulin (responsible for driving blood glucose down after eating) after eating, enhancing the effects of GLP-1 further. The fat loss effects are incredibly impressive [18]. But, it isn’t without side effects, which includes gastrointestinal adverse events such as diarrhea, nausea and vomiting. There is also the risk of medullary thyroid cancer in those predisposed to it, alongside pancreatitis (rare) and gallbladder disorders [19], [20].

Ultimately, this sounds like a ‘miracle drug’, and in many regards, it is in the sense of the fact that it can cause significant fat loss with minimal risks. It is highly available with consultation, though costly. But I pose this question to you: what next?

Medicine exists to treat deficiencies and save lives. Mounjaro is now a new tool added to the toolbox to do just that. But, nobody ever talks about the next step. Often, patients are left on something for life, and we can’t say with certainty what long-term use beyond multi-decades of drugs like semaglutide and Mounjaro will do to your health. Perhaps nothing, but a risk worth taking? The point: a lack of nutritional education.

Consider this scenario: you’ve lost significant weight with Mounjaro, great! You are significantly healthier for it indeed, but coming off of it you perhaps revert to old dietary habits as your appetite creeps back. Your health is not as optimal as it could be too as you simply lacked the fundamental education around nutrition. You still don’t get enough fruits, veg, fibre, water, and so on. You’re still at elevated risk of colorectal cancer and perhaps other diseases, too [21]. Your gut microbiome, though improved, is still not optimal. You have perhaps lost muscle mass too as you didn’t know how best to eat and to exercise more. With any weight rebound, there becomes a potential to develop a psychological dependency to a drug to treat a complex disorder (obesity and overweight) [22]. All because you don’t know how to lose and manage the weight without it. Our view therefore is that these drugs can be used there to kickstart the weight loss process in those who need it the most. But, it should be alongside nutritional education and increased physical activity.

Those who need it the most are patients already Obese, often with type 2 diabetes or other comorbidities, and who are struggling after already trying to lose weight with nutritional plans and failing due to appetite dysregulation. It is a last resort and must have medical evaluation to ensure no potential contraindications exist, too. One such contradiction is a family history of pancreatitis and/or medullary thyroid cancer.

Conclusion

With all the above in mind, drugs like Mounjaro are no longer a ‘miracle’ drug. They are simply a tool in the toolkit. One that absolutely may help to improve our nation’s health, but one that should be reserved for the cases truly needing it. This is also true of TRT: it’s there to treat a disease. But if we can treat it naturally and without pharmaceutical intervention first, we should. If we can’t, fair enough. But weight has far more modifiable factors than hypogonadism often does, and weight management is usually controllable. Thus, drugs like Mounjaro should be a last resort.

Obviously some level of common sense must be applied here; not everything can be treated naturally and without intervention. That is why medical consultation and supervision is vital. So don’t be fooled by celebrities promoting the next weight loss fad. The most important thing you can do is educate yourself and talk to the medical experts. If you are well educated on nutrition and exercise and still struggle, consider behavioural therapy or counselling. Long-term success depends on sustained lifestyle changes.

For more information on how our team of expert doctors can support you in your weight loss journey, please visit our Weight Loss Management service.