The use of medications such as Ozempic (semaglutide) to manage excess weight has become an incredibly contentious topic.
More than any class of medications, they have generated a very polarised set of opinions, with some viewing them as miracle cures while others see them as a moral failing.
Like everything in life.
The answer is never at the extremes but somewhere in the middle.
When a patient asks me, “Do you think I should take Ozempic to lose weight?” here is what I tell them.
Overweight/Obesity.
First, we need to decide if you are medically eligible.
This class of medications is for managing excess fat accumulation that presents a health risk.
Falling into the class of obesity with a BMI of greater than 30 makes this more likely, but so also does having excess visceral fat deposition with significant metabolic consequences at a BMI less than 30.
The distinction here is the metabolic consequences of excess fat causing a health risk rather than focusing on the BMI cutoff.
These medications are not to ‘shed a few pounds’ so that you can be ‘beach-bod ready’.
These are medications to minimise future medical risk.
They are not crash diets to fit into your swimwear.
Like any medication, they come with risks.
And these risks are only worth taking if the risk of not taking them is higher.
But even if you have excess fat accumulation that risks your health, you do not HAVE to take them.
They are simply one of many tools we have to manage excess weight.
It is no more a moral failing to take one of these medications if you have obesity than it is to take a blood pressure-lowering medication if you have high blood pressure.
So if you are a suitable candidate for these medications, you should take them if:
You WANT to.
And on discussion with your doctor you feel the potential benefits outweigh the risks.
But what are the potential benefits and risks?
Let’s go through them.
Weight Loss Potential.
The first-line approach to managing excess weight is properly addressing the lifestyle factors of exercise, nutrition, sleep, and stress.
Even when you are on one of these medications, continuing these fundamentals is essential.
Using a medication such as Ozempic (semaglutide) does not mean you get to abandon all lifestyle efforts.
This is not an either-or situation. It is a matter of using both approaches simultaneously.
In my view, proper exercise and nutrition are undoubtedly the best approaches for preventing excess weight and obesity.
However, for the management of significant excess weight, the utility of exercise and nutrition has less efficacy.
And I use the word ‘efficacy’ very carefully here.
One of the primary criticisms of using these medications for weight loss is that people often say that obesity can just be managed by moving more and eating less.
And they are right.
If you simply eat less and or move more, you will lose weight.
Angus Barbieri was a Scottish man who weighed 456 pounds (207 kg) and lost 276 pounds (125 kg) after fasting for 382 days in a supervised setting. He survived mainly on tea, coffee, water, and vitamins1.
Five years after the fast, he weighed 196 pounds (89 kg).
So yes. Under ideal conditions, significant amounts of weight can be lost and maintained.
This is the definition of ‘Effectiveness’: The degree of benefit under ideal, often controlled circumstances.
How interventions perform in the ‘Real World’ or in uncontrolled circumstances is often very different however.
And we live in the ‘Real World’, not ideal controlled circumstances.
The outcome in real-world circumstances is known as ‘Efficacy’.
Effectiveness tells us what is possible.
Efficacy tells us what is probable.
So What Is The Efficacy Of Diet & Exercise For Weight Loss?
Pretty abysmal after five years.
All diets work. For a while.
When tested across longer time horizons, 50% of people will regain all the weight they lost after two years, and 80% will have regained all of it after five years2.
In a meta-analysis of 30 studies evaluating the utility of lifestyle interventions, the average weight loss at three years was 2.45 kg3.
2.45 Kg is not an insignificant amount of weight, but in the context of what most people need to lose, it simply is not enough for most people.
All lifestyle interventions work.
They just don’t work very well over long periods of time.
They do in ideal circumstances but not in the real world.
Lifestyle measures, including all diets, are very effective but just do not have a very high efficacy.
And efficacy is what matters.
Weight Loss Potential With Obesity Medications.
Ozempic belongs to a class of medications called GLP1 agonists.
Newer therapies that build on this class have already been introduced, including the GLP1 and GIP agonists Tirzepatide (Mounjaro) and Retatrutide, which modifies GLP1, GIP, and Glucagon.
The pace of development is staggering.
The amount of weight loss achieved with these medications is nothing short of astounding.
Ozempic (semaglutide), when tested in those with excess weight, resulted in a 14.9% reduction in weight at about one year compared to controls4.
Tirzepatide (Mounjaro) resulted in a 25% reduction in body weight depending on the trial you choose5.
The average weight of people enrolled at the start of the trial was 109.5 Kg, which means the average weight loss was 27 kg.
The triple therapy Retatrutide has shown similar weight reductions, with 26% of patients losing more than 30% of their starting body weight6.
Obesity and the subsequent metabolic consequences of excess weight pose one of the greatest risks to population-level health globally.
These medications are an important part of that solution.
To date, only bariatric surgery comes close in terms of potential for weight loss.
But Does The Weight Loss Last & What If You Stop The Medication?
As we mentioned earlier, pretty much all lifestyle interventions result in weight loss.
Just not over a longer time horizon.
At two years, when 50% of lifestyle interventions have failed, those on Ozempic (semaglutide) will have maintained the majority of their weight loss7.
Longer-duration trials are ongoing, but for those who continue these therapies, there is no reason to think that significant weight loss will not be maintained.
But What Happens If You Stop These Therapies?
Another way to ask that question is, “What happens if I revert to using only lifestyle interventions?”.
Based on what we have covered so far, I hope you can at least directionally guess what happens.
Yep. The weight loss effect largely dissapears8.
It is on this point that opponents of this class of medication think they have discovered a ‘Gotcha’ moment.
“See. I told you they didn’t work.”
But let me ask you this.
What do you think would happen to someone's blood pressure, LDL cholesterol, or blood glucose if you were to evaluate what happens after you stop their blood pressure, cholesterol-lowering, or diabetes medication?
The exact same thing.
The metric of interest goes back to a pretreatment baseline.
Weight loss medications should be seen no differently.
Remember, these are not ‘Crash Diets’.
They are treatments for excess fat posing potential health risks.
Are These Medications For Life?
No.
They are for use until something better comes along.
And with the pace of development here, medications like Ozempic (semaglutide) will likely appear quaint in the near future.
For some, using these therapies will be enough to kick-start them into being able to solely manage excess weight with lifestyle approaches, but I suspect for the majority, in one form or another, therapy will be required.
But What About The Side Effects?
All medications have potential side effects.
Even over-the-counter therapies such as paracetamol or ibuprofen can have potentially lethal side effects.
This is why we need to keep these medications for when the potential health benefits outweigh the risks.
These are medications.
Not ‘Lifestyle Injections’.
The primary set of side effects from this class of medications include:
Nausea
Vomiting
Diarrhoea
Constipation
There are other more potentially serious side effects, including pancreatitis, but again, like every medication, most side effects are not serious, but all have the potential for very serious side effects.
Depending on the studies you look at, the most common side effect is nausea, with about 20% of patients experiencing some for the first 5 to 6 months, which is when most of the dose titrations of the medication occur.
For most patients, the side effects, if any, are tolerable.
But for some, they simply cannot tolerate the medication or just do not lose sufficient weight to justify continuing the therapy.
But What About The Long-Term Side Effects?
These are new medications.
Therefore, our long-term data on the potential for side effects is limited.
But we know one thing for certain.
The long-term side effects of excess weight causing metabolic dysfunction are very serious and are linked to higher rates of heart attack, stroke, high blood pressure, diabetes, fatty liver disease etc. etc., etc.
Both sides of the equation have the potential for long-term serious side effects, but the long-term side effects of excess weight are very well known.
Other Challenges.
Cost and access are among the biggest obstacles to broader scale use of these medications.
But that has not dampened demand.
Because of these issues, people are reverting to unregulated compounded versions of these medications, which, in my view, is simply not a good idea and comes with substantial risk.
Many patients also find it hard to access starting doses, which means they frequently go without the therapy.
The self-pay cost of these therapies is variable depending on which country you live in.
In Ireland, the usual price range is about 160 euros per month.
In the US, this can be anywhere from $1000 monthly and upwards.
Both the cost and access issues will be resolved in time.
But for now, they remain significant issues.
So, Should You Take Ozempic Or Other Weight Loss Medication In The Same Class?
The answer is: If you have excess weight posing a potential health risk and you WANT to with full knowledge of all the possible benefits and drawbacks.
Amazingly, we are only in the early days of this class of medications, but already, we have access to therapies that make life-changing differences.
They are not for everyone.
For some people, lifestyle interventions focusing on nutrition, exercise, sleep, and stress management will be enough.
But when lifestyle measures are inadequate in isolation, we now have access to therapies that work consistently, over long time horizons and with a very reasonable side effect profile.
These medications are tools.
Nothing else.
The question is whether that tool is right for you and what task you are trying to solve.
When You Are Ready, Here Is How We Can Help.
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In Case You Missed It:
https://en.wikipedia.org/wiki/Angus_Barbieri%27s_fast#:~:text=Angus%20Barbieri%20(1938%20or%201939,Maryfield%20Hospital%20for%20medical%20evaluation.
Maintenance of Lost Weight and Long-Term Management of Obesity. Med Clin North Am. 2018 Jan;102(1):183-197.
Intensity and duration of lifestyle interventions for long-term weight loss and association with mortality: a meta-analysis of randomised trials. BMJ Open. 2019 Aug 18;9(8):e029966.
STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002.
Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med. 2023 Nov;29(11):2909-2918.
Retatrutide Phase 2 Obesity Trial Investigators. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med. 2023 Aug 10;389(6):514-526.
Two-year effect of semaglutide 2.4 mg on control of eating in adults with overweight/obesity: STEP 5. Obesity (Silver Spring). 2023 Mar;31(3):703-715.
STEP 1 Study Group. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022 Aug;24(8):1553-1564.
Thank you - very comprehensive, and right down the middle. Appreciate the info!
Thanks for this very comprehensive and rational exploration of obesity management Paddy.