Weight loss drugs like Ozempic are making people move less, and that’s bad on multiple levels

It’s been more than two years since I wrote my miniseries on GLP-1 agonists – the weight loss injections that have taken the world by storm – and one year since I published an update on the emerging risks of suicidal ideation and irreversible blindness associated with use of Ozempic, Wegovy and their ilk.

In the mean time, use of GLP-1 agonists has exploded. Between 2020 and 2025, total Australian sales increased almost tenfold. Semaglutide (Ozempic, Wegovy) accounts for the lion’s share of prescriptions, while tirzepatide (Mounjaro) use is surging:

Roughly half a million Australians – almost two per cent of the population – are currently using GLP-1 agonists, and supply-demand modelling performed by the multinational investment bank Morgan Stanley in 2024 predicted that up to 40 per cent of Australians could be on the GLP-1 train by 2030.

GLP-1 agonists reduce spontaneous physical activity

Bearing in mind this burgeoning use, research presented at the 2026 annual conference of the Endocrine Society is quite alarming. In a poster presentation titled ‘Losing Pounds, Not Gaining Steps: The Paradox of GLP-1 Receptor Agonist Therapy’, researchers analysed data from 753 participants in the All Of Us Research Program, who had Fitbit activity data from both before and after they began using GLP-1 agonists to lose weight.

Contradicting the widely-held assumption that people will exercise more after losing weight, because a lighter body is easier and more enjoyable to move around, participants took an average of 560 fewer steps per day after initiating GLP-1 drugs (dropping from an average of 5047 to 4487 steps), and performed 5.7 fewer minutes of moderate-to-vigorous physical activity per day (from an average of 27.9 minutes per day down to 22.2 minutes/day). Step count is a decent proxy for spontaneous movement, while moderate-to-vigorous physical activity reflects intentional exercise.

Male participants experienced greater declines in both daily steps and moderate-to-vigorous physical activity than females. Participants suffering from musculoskeletal pain also decreased their daily step count significantly more than those not in pain. This is quite a counterintuitive finding. We would expect weight loss to ease painful joints and sore muscles, thus facilitating higher levels of activity. And considering that almost 82 per cent of participants reported suffering from musculoskeletal pain, this finding is also highly concerning.

The authors concluded that

“In this real-world cohort, initiation of GLP-1 RA [receptor agonist] therapy in obese patients led to a significant decrease in daily steps and MVPA [moderate-to-vigorous physical activity], with males and those with MSK [musculoskeletal] pain experiencing the greatest declines. These reductions in activity were not influenced by age, morbid obesity, stroke, or heart failure status. These findings suggest that weight loss alone may not promote increased physical activity, highlighting the need for future studies to explore targeted interventions that encourage physical activity alongside pharmacologic therapy.”

Losing Pounds, Not Gaining Steps: The Paradox of GLP-1 Receptor Agonist Therapy

Why do GLP-1 agonist users move less?

The researchers were simply analysing movement data recorded by Fitbits, so they were not able to ascertain the reasons for participants’ decline in physical activity. A few possibilities immediately spring to my mind though:

1. Moral licensing. Also known as self-licensing and the licensing effect, this is a fascinating and well-documented phenomenon by which people give themselves permission to do something bad, after they’ve done something good. Think of the dieter who ‘treats herself’ to an indulgent dessert after a week of healthy eating – that’s moral licensing. So people may perceive that since they’re already doing something good for their weight by taking the drug, they can feel free to do something bad for their weight by being more sedentary.
2. Sarcopenia. GLP-1 agonists cause sharp reductions in muscle mass – far more so than regular dieting-induced weight loss. In fact, muscle loss can account for up to 40 per cent of weight lost on these drugs. With less muscle, physical activity feels considerably harder and less rewarding. The accompanying frailty can also reduce people’s confidence in undertaking exercise, due to fear of falling or suffering an injury.
3. Depression and reduced dopamine signalling. I previously discussed the evidence that GLP-1 agonists may induce depression and suicidal thoughts, or just make users feel ‘blah’, by reducing dopamine signalling. Although dopamine has long been thought of as a ‘pleasure chemical’, it is more accurately characterised as playing a key role in reward. The brain’s reward system utilises dopamine to evoke feelings of enjoyment and reinforcement, which then motivate us to continue or repeat the behaviour. Dopamine is also crucially involved in the initiation and regulation of movement. So it’s easy to see how GLP-1 agonist-induced downregulation of dopamine signalling could lead people to become less physically active.

Whatever the cause (or causes) may be of the decreased physical activity observed in people using GLP-1 agonists, the implications are disturbing. The authors of the new report point out that “long-term weight control is more effective when combined with regular exercise”… but if GLP-1 drugs lead to reduced physical activity, weight regain is far more likely. And we already know that roughly 10 per cent of people quit taking GLP-1 agonists because they can’t tolerate the side-effects, and they start regaining weight immediately.

Furthermore, weight loss plateaus after people have been on these drugs for a bit over a year, even if they continue using them. So at this stage GLP-1 agonist users are in a truly invidious position: The drug is no longer helping them to lose weight, but if they stop taking it they’ll gain back the weight they lost, which will now be much harder to shift because they’ve lost muscle mass and hence dialled down their metabolic rate.

In a nutshell, if this preliminary research is confirmed in larger studies, what we’re looking at is the prospect that tens of millions of people may have significantly reduced muscle mass as a direct consequence of using GLP-1 agonists, and that they will find it extremely difficult to do the volume of exercise required to halt or reverse this loss of muscle tissue, setting them up for not only weight regain but frailty and increased risk of bone fractures.

The exercise-mood connection

Furthermore, there’s a bidirectional relationship between physical activity and what researchers call affective well-being, which incorporates experiencing positive emotions, feeling energised, and feeling well and content. Drawing on studies which collected both movement data from accelerometers (like Fitbit), and self-ratings of affective well-being on smartphone-based electronic diaries, researchers analysed 67 datasets from 14 countries worldwide, incorporating data from 8223 participants.

They found that when individuals are more physically active than their own average, they report higher affective well-being at their next self-assessment. And on average, more active participants exhibit higher affective well-being compared with less active participants.

Conversely,

“When a participant exhibited higher AWB [affective well-being] than their own average, their subsequent PA [physical activity] was higher compared with assessments with lower prior AWB (within-person association), and on average, participants with higher AWB showed higher overall levels of PA compared with participants with lower AWB (between-person association).”

An individual participant data meta-analysis of how physical activity relates to affective well-being in daily life

Put concisely, the more physically active you are, the more upbeat you will feel, and the more upbeat you feel, the more physical activity you’ll do. It’s almost like we’re designed by Mother Nature to move our bodies around on a regular basis. Huh!!!!

The finding that “adults with a lower BMI reported higher valence [feeling well and content] after being more physically active than usual compared with adults with a higher BMI” is particularly interesting in the light of the research discussed above, which found that people became less active after starting to use GLP-1 agonists for weight loss. Under normal circumstances, slimmer people get more of a pick-me-up from exercise than the more well-upholstered. This stands to reason: exercise is likely to be less uncomfortable and more enjoyable if you’re not encumbered by excess fat. But if GLP-1 drugs squelch your dopamine signalling, you won’t reap this benefit of finding exercise more rewarding as you drop weight.

Here’s another finding that caught my eye:

“The data suggest that individuals exhibiting higher average negative affective states show stronger reductions in their momentary negative affective states after engaging in more PA than usual compared with individuals with low negative affective states (r = −0.13, 99.2% CI −0.23 to −0.04). For positive affective states, the data suggest that individuals exhibiting lower average positive affective states show stronger increases in their momentary positive affective states after engaging in more PA than usual compared with individuals with high positive affective states.”

An individual participant data meta-analysis of how physical activity relates to affective well-being in daily life

Translation: exercise is particularly good at busting negative emotions in those most prone to them, and likewise, is more effective at bolstering positive emotions in those who habitually experience them less often. Once again, if GLP-1 agonists squelch physical activity, they will rob users of these life-enhancing effects on their affective well-being.

Of course, if you’re taking a GLP-1 agonist drug, you could use this information to motivate you to exercise more, even if it feels less rewarding. But it’s tough to maintain that motivation to do something that you don’t feel you’re getting much out of, over the long term. And of all the nasty adverse effects of GLP-1 drugs, this one may well turn out to be the most impactful of all.

But hey, if you’re a sociopathic Big pHarma exec, that’s good news, right? Think of all the extra customers you’ll generate for your antidepressants!

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