A Weighty Issue: The Tricky GLP-1 Questions

Estimated reading time: 25 minutes

GLP-1 medications are not really my usual subject matter.

Most Movement Literacy articles explore movement, fitness, recovery, pain, stress, ageing and the wonderfully complicated ways our bodies adapt to life.

But GLP-1s have become impossible to ignore.

Depending on who you ask, they are either one of the most important medical breakthroughs of our generation, an overhyped weight-loss fad, a powerful treatment for chronic disease, or the beginning of a very interesting social experiment.

Probably all four.

Before we go any further, a quick note on terminology. Strictly speaking, GLP-1 is a naturally occurring hormone produced by the body. The medications discussed in this article are drugs that mimic or enhance some of its actions.

In everyday conversation, however, the term “GLP-1” has become shorthand for the medications themselves. To avoid turning this article into a pharmacology lecture, I’ll generally use “GLP-1” in the way most people do. Where the distinction matters, I’ll be more specific.

As I started researching this topic, I quickly discovered there was far more science than could comfortably fit into a normal blog.

And far, far more questions because of the far more science.

Rather than turn this into a small textbook, I’ve done something a little different.

I am going to focus on the questions people are actually asking:

the uncomfortable questions, the controversial questions and the ones that “don’t yet have clear answers”.

To honour the closet academics amongst us (myself included), I have created hyperlinks to the dry, heavily-referenced sciency-stuff behind all my claims. Feel free to skip them entirely or disappear down the rabbit hole, if that’s your thing.

I was hoping this blog would end with a simple answer.

It didn’t.

The deeper I disappeared down the GLP-1 rabbit hole, the more I encountered phrases such as “we don’t fully understand the mechanism”, “more research is needed”, and “the long-term effects remain unclear”. Not exactly the neat conclusion I was looking for.

What I did find was a group of medications that appear remarkably effective for many metabolic diseases, but which also raise some important questions that are often lost beneath the before-and-after photos and social media hype.

So instead of telling you whether you should take a GLP-1, I’ve focused on the elephants in the room: the questions I would want answered before deciding whether to take one myself.

You may not agree with all my conclusions. To be fair, I’m not entirely sure I agree with all of them either.

But if this article leaves you asking better questions, then it has done its job.

I have many questions. Some may not sit so comfortably with everyone.

If one particular elephant is already stomping around in your head, feel free to jump straight to it.

• Are GLP-1s treating the root cause or just the symptoms?
• What if you just consider yourself “overweight”?
• Could we use GLP-1s preventatively?
• Should we be worried about the long-term use of GLP-1s?
• Could you become GLP-1 resistant?
• What are you supposed to do when you get to your goal weight?
• Can you taper off GLP-1s?
• People talk about microdosing – what exactly is it?
• And oh dear – it has to be brought up eventually … the “vanity drug” issue.

And because this is a lengthy blog, some additional fast-forwards if you need them:

THE HOW TO

• What do GLP-1s actually do?
• What are GLP-1s prescribed for?
• The medication is not the whole treatment

THE SCIENCE

Conclusion

Since I practice in the field of bodywork, where we look at both symptoms and causes, this question naturally interests me.

For Type 2 diabetes (T2D), the answer is relatively straightforward. GLP-1 medications improve blood glucose control, stimulate insulin release when needed, reduce glucagon production and often improve insulin sensitivity through weight loss. They appear to address several of the biological processes driving the disease.

Obesity is a much trickier conversation.

If obesity were simply a matter of eating too much, then a medication that reduces appetite might look like symptom management. Hungry? Take a drug that makes you less hungry.

But modern obesity research suggests that body weight regulation involves a complicated network of hormones, brain signalling, energy expenditure, reward pathways and genetics. In that view, excessive hunger may not be a symptom at all. It may be part of the disease process itself.

The challenge is that scientists still do not fully understand why some people gain weight more easily than others, why GLP-1 medications work remarkably well for some people and less well for others, or even whether chronic insulin dysregulation sits closer to the root of the problem than excess body fat itself.

Which leaves us with a rather large elephant standing in the room:

If we don’t fully understand what causes obesity, how can we be completely certain that we’ve identified its root cause?

Perhaps they are correcting an important biological dysfunction.

Perhaps they are interrupting one pathway among many.

Or perhaps the answer depends on who is taking them and why.

As with many things in the science of the body, the more you learn, the less black-and-white the answer becomes.

Back to the other Elephants In The Room

There is a difference between using GLP-1s for obesity and using them for being “overweight.” On paper, overweight and obesity are separate categories. But GLP-1s are not generally positioned as “BMI 25 and feeling annoyed with your jeans” drugs. They are approved for obesity, or for being overweight when there is at least one additional weight-related health condition — for example T2D, high blood pressure, abnormal cholesterol, or cardiovascular risk.

And this is where the elephant starts waving both arms.

Because “overweight” is a huge category. It can include someone with rising glucose and visceral fat, metabolic dysfunction and increasing cardiovascular risk. It can also include someone who is metabolically healthy but would simply prefer to be smaller.

Those are not the same conversations.

The more the reason shifts from treating metabolic disease toward treating appearance, the less clear the risk-benefit equation becomes.

If GLP-1s are that good at improving metabolic health, another elephant starts waving frantically from the corner of the room: why wait until someone has developed a metabolic disease before using them? This is done fairly routinely with other lifestyle diseases, for example, treating high blood pressure and cholesterol early in order to prevent a heart attack.

Salamah et al. (2024) found that GLP-1s, together with lifestyle interventions, could manage and even reverse prediabetes whilst patients remained on treatment.

What remains less clear is how many people maintain those benefits after the medication is stopped.

And to nod at that waving elephant again:

If elevated insulin is the earliest measurable problem, should we not be treating insulin resistance before we reach the stage where GLP-1 medication becomes necessary?

Of course, if we’re going to talk about using GLP-1s preventatively, we also need to talk about how comfortable we are using them for longer. Should we be worried?

The short answer is: probably less than social media would have us believe, but perhaps more than some of the marketing would suggest.

In all likelihood, it depends on which GLP-1 we’re talking about.

One perspective on this issue is actually fairly reassuring. Liraglutide, which is specifically approved for the treatment of obesity, has been around since 2014. A lot of people have taken it. Researchers argue that if it were causing some large, previously unnoticed problem, we would probably have seen signs of that by now.

The broader family of GLP-1 medications has an even longer track record. They’ve been used in the treatment of T2D since 2005, and more than 20 million people worldwide have used them.

In fact, Druker (2022) specifically reviewed concerns relating to pancreatitis, pancreatic cancer, thyroid cancer, cardiovascular risk and various other scary-sounding possibilities, concluding that the available evidence supports both their effectiveness and safety.

That doesn’t mean you should ignore new symptoms, if you start taking a GLP-1. As the GP I spoke to pointed out, pancreatitis remains a recognised, albeit uncommon, potential adverse effect of GLP-1 therapy. If you develop persistent or unusual abdominal pain while taking one of these medications, do contact your prescribing doctor so that appropriate investigations can be carried out. Being aware of a potential side effect is not the same thing as expecting it to happen.

End of the story then?

Not quite.

Because those wearing white coats still have a few unanswered questions on their clipboards.

Semaglutide, for example, was only approved for the treatment of obesity in 2021. Not yesterday, but not in the sepia era either.

And then there is the brain.

GLP-1 receptors are scattered throughout the brain, and scientists are still trying to understand the full implications of that. Our own naturally produced GLP-1 disappears very quickly. The synthetic versions hang around much longer. Does that matter? Perhaps. We’re still waiting for time and data to answer that one.

Now before anybody panics and throws their injection pen into the nearest sugar-free yoghurt, “we don’t fully understand it yet” is not the same thing as “it’s dangerous.”

It simply means that some questions can only be answered with time.

Which brings me to the question I would personally ask:

If a GLP-1 could significantly improve my health today, would I be willing to accept a small possibility that we discover something unexpected twenty years from now?

Because that’s really the calculation.

Very few medications come with a guarantee.

The question is whether the risks of taking the medication are greater or smaller than the risks of the condition you’re trying to treat.

As with many things in life, too much of a good thing can lead to diminishing returns.

Think caffeine, social media, that song you loved until you played it 437 times.

The underlying biology may differ, but a common theme in physiology is that repeated exposure to a stimulus can reduce our responsiveness to it.

Could the same thing happen with GLP-1s?

After all, some people report that their appetites are no longer suppressed or that they stop losing weight after they have been on the medication for a while. And it has been shown in some animal studies that if the GLP-1 signal is activated over and over again, the body can start to pay less attention to it. The message is still there, but its impact may gradually weaken.

So, it is not an unreasonable query to ponder.

I have struggled to find research showing that people become clinically “GLP-1 resistant” in the same way that we talk about insulin or leptin resistance. What I did find was quite a bit of discussion about something else entirely:

the body’s remarkable ability to defend itself against weight loss.

And that brings us to the rather awkward topic of set points…

According to set-point theory, the brain and appetite-regulation systems may react to weight loss as though you’ve taken a wrong turn, increasing hunger and reducing energy expenditure in an effort to guide you back towards your previous weight.

This is one reason many people find maintaining weight loss harder than losing it in the first place.

Can we change the body’s set point?

This is where things become slightly tricky.

Garvey (2022) argues that certain life events such as pregnancy, menopause and disease may alter the body’s defended weight. However, he also notes that lifestyle interventions and obesity medications do not appear to permanently reset the body’s weight-regulation system.

Yikes.

This raises a rather important question:

If the body is defending a higher weight, what happens when you finally reach your goal weight?

And the answer is one of those highly technical medical terms:

“It depends.“

If you were taking a GLP-1 medication to treat a chronic disease such as T2D or obesity, it is likely that treatment would continue long term, because the medication is not simply helping with weight loss; it is also treating an underlying metabolic dysfunction.

This is particularly relevant to obesity.

Current evidence suggests that GLP-1 medications help counter many of the biological processes that promote weight gain, but they may not eliminate them. Once the medication is discontinued, satiety may decrease, hunger may increase, energy expenditure may remain lower and the body may continue defending a higher weight.

There is another wrinkle.

When people lose weight on a GLP-1, they do not lose only fat. Some lean tissue, including muscle mass, is typically lost as well. Because muscle is metabolically active, this may contribute to the reduction in energy expenditure that often accompanies weight loss.

This is one of the reasons why adequate protein intake and resistance training are strongly encouraged during GLP-1 treatment. The goal is not simply to become lighter; it is to lose as much fat and as little muscle as possible.

Not everyone regains all of the weight they lost, but the odds are not especially encouraging.

Around 83% of people regain more than 20% of the weight they lost.

Hmmmmm…

If you were using a GLP-1 as a temporary tool to lose “those last few kilos,” those statistics may give you pause.

On the other hand, if you are taking a GLP-1 to manage a chronic disease such as T2D, obesity or cardiovascular disease, weight regain after stopping the medication may reveal more about the biology of the condition than about any failure of the drug itself.

Which raises another interesting question:

If someone loses 20 kg on a GLP-1 and later regains 10 kg, have they failed? Or are they still 10 kg better off than where they started?

The answer may depend on whether your goal is perfection or improvement.

Remaining healthier than before treatment may be a far more meaningful measure of success than maintaining every kilogram of weight loss indefinitely.

And therein lies the dilemma.

Whether GLP-1s are a short-term intervention or a long-term treatment may depend less on the medication itself and more on the condition they are being used to treat.

Given the rather discouraging statistics on weight regain, this is probably the next question most people ask.

Possibly.

And that answer is more encouraging than it was a few years ago, after all, if the medication has been helping to control appetite and body weight, perhaps giving the body time to adjust would make sense.

Preliminary evidence presented at the 2024 European Congress on Obesity suggested exactly that. Patients who gradually tapered semaglutide while receiving ongoing lifestyle support were able to maintain their weight loss for several months after stopping treatment.

However, before everybody starts planning their tapering schedule, it’s important to remember that these findings are still preliminary. Tapering as a strategy to prevent weight regain has not yet been confirmed in large randomised clinical trials.

So at the moment, tapering sits in an interesting category:

Promising? Possibly.

Proven? Not yet.

It’s one of the ideas gaining traction on social media and in patient communities.

The term generally refers to taking doses below those studied in clinical trials and approved by regulators.

Why would you do that?

Usually to reduce side effects, lower costs, maintain weight loss or use the medication as a long-term maintenance strategy.

On the surface, it sounds fairly sensible. If a little works, perhaps a little less will work too.

The catch?

Nobody can quite agree on what a GLP-1 microdose actually is, which, as you can imagine, makes studying it rather difficult.

Unlike the approved dosing schedules studied in clinical trials, there is currently no standard definition of a microdose. There is also very little research examining whether doses below those tested in clinical trials are effective or safe, particularly when used as a long-term weight-maintenance strategy.

The same uncertainty applies to people experimenting with intermittent use rather than continuous treatment.

There are various logical arguments for using GLP-1s as a temporary support whilst building healthier lifestyle habits. For example, someone might use a GLP-1 for a period of time whilst improving their nutrition, exercise habits and lifestyle, then discontinue the medication and restart it if the wheels begin to fall off.

Whether it works is another matter.

When we look at the available evidence, the current scorecard looks something like this:

So right now, lots of people are talking about it.

The researchers are still busy taking notes.

Treating disease versus treating appearance is where much of the current ethical and medical debate sits.

There are some very strong opinions that GLP-1s are not intended for losing “those last few kilograms” to finally button up your jeans from 2018. The argument is that these individuals are generally not experiencing the health consequences associated with obesity or metabolic disease, so the risk-benefit calculation looks rather different.

And that’s where things become interesting.

Would you put control of those 10 kilograms in the hands of a needle?

Some people would answer yes.

Some would answer no.

Neither answer is automatically wrong. It entirely depends on what those 10 kilograms are costing you.

But it does force us to think carefully about what problem we are trying to solve.

And while we’re discussing trade-offs, there is one final irony worth mentioning.

If GLP-1 medications reduce the reward value of food, could they also reduce the reward value of other pleasurable and normal activities, including sex?

At present, the answer appears to be… (drumroll please)

Possibly. But we don’t know yet.

Some people taking GLP-1 medications have reported a reduced libido or difficulty achieving orgasm, while others report improvements in their sex lives following weight loss and improved metabolic health.

In other words, the evidence is currently mixed.

Still, if your primary motivation for taking a GLP-1 is to look sexy for someone else, only to discover that sex itself has become less interesting …

Well.

That would be an awkward conversation.

Back to all the Elephants In The Room

One of the reasons GLP-1s have generated so much excitement (and confusion) is that they don’t just work in one place. Receptors for GLP-1 are found throughout the body, including in the brain, stomach, gut, pancreas and heart.

As a result, GLP-1 medications do far more than simply promote weight loss. Among other things, they:

• Help regulate blood sugar by improving insulin function and reducing glucagon release.
• Slow the rate at which food leaves the stomach.
• Help regulate blood pressure and cholesterol.

Taken together, these effects help explain why GLP-1 medications can be useful in the treatment of T2D, obesity and cardiovascular disease.

Established Uses

Despite all the social-media chatter, GLP-1 medications were originally developed to treat T2D. Obesity treatment came later.

In people with T2D, GLP-1 medications improve blood sugar control and reduce the risk of several diabetes-related complications.

In people with obesity, GLP-1 medications are used alongside lifestyle interventions to improve weight loss and reduce the health risks associated with excess adiposity.

Several GLP-1 medications have also been shown to reduce cardiovascular risk in people with obesity, those who are overweight or who have T2D.

Some GLP-1 medications are now approved for additional conditions. For example, tirzepatide is approved for the treatment of moderate-to-severe obstructive sleep apnoea.

Emerging Uses

Researchers are also investigating GLP-1 therapy for conditions such as Parkinson’s disease, dementia, addiction and other neurological disorders.

Obviously, I cannot prescribe GLP-1 medications.

What I can do is explain the different drugs, the brand names you are likely to hear about, the conditions they are approved to treat and how they are typically administered.

Generic Name	Brand Name	Indicated For	Typical Dosing*
Liraglutide	Victoza	T2D	Daily injection
Liraglutide	Saxenda	Obesity	Daily injection
Semaglutide	Ozempic	T2D	Weekly injection
Semaglutide	Wegovvy	Obesity	Weekly injection
Tirzepatide**	Mounjaro	T2D	Weekly injection
Tirzepatide**	Zepbound	Obesity	Weekly injection

*Most are administered as a small injection under the skin, although an oral form of semaglutide is also available.

**Unlike the other medications listed above, Tirzepatide acts on both GIP and GLP-1 receptors

Whichever medication is prescribed, one point is worth remembering…

If you were hoping I was about to tell you that one weekly injection means you never have to think about optimal nutrition, exercise or sleep again ….

Well then, you don’t know me very well.

Sorry to disappoint, but no.

In reality, the major clinical trials combined medication with counselling around nutrition, physical activity and behaviour change.

The injection was intended to be one component of treatment, not the entire treatment plan.

Because these medications reduce appetite, what you eat becomes even more important. Adequate protein intake, fruit, vegetables, whole grains and healthy fats remain essential.

Exercise also remains a cornerstone of care, particularly resistance training, which helps preserve muscle mass and strength during weight loss.

And that’s important because when people lose weight, they don’t just lose fat. Some of the weight lost is muscle, and muscle is valuable metabolic real estate that we want to hang on to wherever possible.

Perhaps most importantly, a smaller body is not automatically a healthier body.

The goal is not simply to make the number on the scale smaller.
The goal is to improve overall physical and mental health.

Like all medications, GLP-1s come with side effects. The most common side effects include:

• nausea
• vomiting
• diarrhoea
• constipation
• indigestion.

Fortunately, these are usually mild to moderate and often improve with time. One reason doctors typically start with a low dose and gradually increase it is to help the body adjust and minimise these effects.

Interestingly, some of the strategies used to reduce the side effects sound remarkably like great lifestyle advice:

• eat smaller meals
• eat more slowly
• stay hydrated
• get enough fibre
• limit alcohol.

Long-term GLP-1 use has also been associated with small increases in heart rate in some people, so that is something to discuss with your prescribing clinician.

You may also have come across concerns about depression, anxiety and suicidal thoughts. These concerns were raised by early safety reports, but larger studies have not confirmed a clear increase in risk, and regulatory reviews have not established a causal link. Even so, anyone with a history of mental health challenges should be appropriately monitored while taking these medications.

One practical point that was not highlighted in any of the articles or podcasts I reviewed was raised by the GP I consulted with. As GLP-1 medications slow gastric emptying, they need to be stopped before planned surgery. The concern is that food may remain in the stomach for longer than expected, increasing the risk of aspiration during anaesthesia. This is something your surgeon and anaesthetist need to know about well in advance of any procedure.

The GP also raised a concern about the reports of irreversible neurological blindness that may be associated with GLP-1 use.

A valid worry for sure, but it also highlights an important reality of medicine: researchers and clinicians often have to view the same issue through different lenses.

Researchers ask, “How often does this happen?” Clinicians ask, “Could this happen to the patient sitting in front of me?” Those questions can sometimes lead to different levels of concern, but they are not actually in conflict. One perspective helps us understand the risk across millions of people; the other reminds us that every statistic ultimately represents an individual.

And if there is one theme that seems to crop up repeatedly in the GLP-1 conversation, it is this: the science is advancing so rapidly that researchers, clinicians and patients are often trying to make sense of new information in real time. Sometimes the answers are clear. Sometimes they are still catching up with the questions.

As with most medications, the goal is not to pretend side effects do not exist.

The goal is to understand them, monitor them and weigh them against the potential benefits of treatment.

Back to all the Elephants In The Room

You may have noticed the hyperlinked Science Notes scattered throughout the Elephants in the Room and the How-To section. If you’d like to disappear down the science rabbit hole, here they are again in one convenient place:

Science Note 1:  How Do GLP-1 Medications Work?

Science Note 2:  What Conditions Are GLP-1 Medications Used to Treat?

Science Note 3:  Are GLP-1s Treating the Root Cause or Just the Symptoms?

Science Note 4:  Overweight vs Obesity and GLP-1 Eligibility

Science Note 5:  GLP-1 Medications Are Not the Whole Treatment

Science Note 6:  Side Effects and Safety Considerations

Science Note 7:  Should we be worried about the long-term use of GLP-1s?

In conclusion then, I can honestly say I am still somewhat discombobulated.

If I were considering taking a GLP-1, the first question I would ask myself is:

What metabolic problem am I actually trying to treat?

If the answer is T2D, obesity, cardiovascular risk, fatty liver disease, chronic inflammation, or one of the other conditions for which these medications are proving beneficial, then the risk-benefit equation starts to make sense.

If the answer is simply “I would like to lose some weight”, I am less convinced. Not because the drugs don’t work — clearly they do — but because every medication involves trade-offs. For me, wanting a smaller number on the scale would not automatically outweigh the known side effects and the unknowns that still remain.

That is why I find myself agreeing with Howard Luks and Ben Bikman, who argue that GLP-1s may be better understood as medications that improve metabolic health rather than simply “weight-loss drugs”. Weight loss may be one of the outcomes, but not the goal, because weight loss is not the whole story.

I also agree with Luks’ observation that the science is moving faster than the public’s understanding. New benefits are being discovered, new uses are being explored, and new questions keep emerging. That alone is a good reason why these medications should be prescribed and monitored by healthcare professionals rather than treated as the latest wellness accessory.

And therein lies my final dilemma.

The next generation of GLP-1 medications is already on the horizon and appears likely to be even more effective for weight loss, insulin resistance, cardiovascular disease and liver health than the current generation. That is exciting.

At the same time, throughout researching this article I repeatedly encountered phrases such as “we don’t fully understand the mechanism”, “more research is needed”, and “long-term data are limited”. Those statements are not red flags; they are simply how science works. But they do remind us that these medications are still relatively young.

So where have I landed?

GLP-1s appear to be extraordinarily promising medications for people with genuine metabolic diseases. Whether they are equally appropriate for everyone who would simply like to be thinner remains, in my mind, a much more complicated question.

As for whether the scientist developing the next generation of GLP-1s will have answered all the “I don’t knows” before releasing them … I suspect a few of those questions will still be coming along for the ride.

References with supporting statements

My thanks to Dr Janine Rivelland, whose willingness to chat through some of the thornier GLP-1 questions helped keep me honest and grounded in clinical reality. (personal communication, June 16, 2026).