GLP-1 receptor agonist drugs (such as Ozempic, Wegovy, Mounjaro, and others) have a good reputation for working well, and the most talked-about downside is that they often have unpleasant side effects:

Most People Who Start GLP-1 RAs Quit Them Within A Year (Here’s Why) ← there are 4 main reasons

…and of course, some do work better than others: Better Than Ozempic?

As with almost any drug, some people are simply “non-responders”, meaning that for some reason (often a genetic factor, often not known for sure why), the drug will simply not work as it does for most people.

For GLP-1 receptor agonists, there is a portion of the general population for whom they simply will not work, and so far there is no known way of predicting it (probably at someone point it’ll be figured out, and this writer’s money would be on it being either a SNP mutation or a microbiome thing). So, you roll the dice, you take the GLP-1 drug, you wait and see, and there’s a 15% chance (that doesn’t sound like a lot, but it’s about 1 in 6, in other words, the same probability as rolling a “1” on a fair, six-sided die).

You can read about how that can go, here: Ozempic didn’t work for me. I was furious—and ashamed

But why?

The key is in why you are overeating in the first place (and if you’re looking to lose weight and/but are not overeating, then probably GLP-1 drugs are not for you, since that is primarily how they work).

In few words:

• If you are overeating in response to the sight and/or smell of tasty food, then probably you will benefit well from GLP-1 RAs in the long-term
• If you are overeating for emotional reasons (e.g. because of depression, or as a coping strategy to deal with stress/anxiety, for example) then probably GLP-1 RAs cannot be replied on to help you.

By “cannot be relied on” does not mean you will necessarily be a “non-responder” as described above, but it does mean that it’s likely your results will be intermittent at best. Which, after all, is not a big improvement on regular yo-yo dieting, an approach that is famously Not Good™.

Indeed, per the categories in the study we’re about to cite:

• Emotional eaters (eating due to negative feelings, not hunger) responded best to glp-1 drugs, showing greater weight loss and better blood sugar improvements
• External eaters (eating because food looks or smells appealing) were less likely to benefit in the long term
• Restrained eaters (deliberately restricting diet to lose weight) exercised more restraint temporarily, but returned to baseline by 12 months

Notably, all three categories of eaters here were people with type 2 diabetes—in other words, the very people that GLP-1 drugs were first developed to help, before they took off as weight-loss drugs.

So in theory, these should be the people for whom GLP-1 RAs work best—and yet, as we see, it’s still not always so, and is highly dependent on what goes on between one’s ears.

You can read this paper in full, here: Association between eating behavior patterns and the therapeutic efficacy of GLP-1 receptor agonists in individuals with type 2 diabetes: a multicenter prospective observational study

Want a different approach?

It is possible to get many of the effects of GLP-1 RAs without taking GLP-1 RAs, by enjoying foods that increase incretin, a hormone group (the most well-known of which is GLP-1) that slows down stomach emptying, which means a gentler blood sugar curve and feeling fuller for longer. It also acts on the hypothalamus, controlling appetite via the brain too (signalling fullness and reducing hunger).

For what foods to focus on, see: 5 Ways To Naturally Boost The “Ozempic Effect” ← this is from Dr. Jason Fung, who is perhaps most well-known for his work in functional medicine for reversing diabetes, and he’s once again giving us sound advice about metabolic hormone-hacking with dietary tweaks!

Or to curb emotional eating specifically, check out: Emotional Eating And The Five Pillars Of Craving Control

Or for a deeper dive, you might like this book we reviewed not long back:

Breaking Free from Emotional Eating – by Geneen Roth

Take care!

Exercise is, of course, vitally important for many aspects of health. So, can it be replaced by a pill?

And the answer is: in part, at least!

Here’s how…

Trick the muscles; trick the brain

First, what this won’t do:

• Give all the cardiovascular benefits of exercise
• Give all the strength (muscular or skeletal) benefits of exercise

You may be thinking: isn’t that everything then?

And no it isn’t, because the word “all” was doing a fair bit of heavy-lifting (so to speak) in those bullet points.

For example, there are a lot of physiological benefits, such as to muscle metabolism and knock-on effects in brain health (not just due to improved circulation, but also due to assorted chemicals being released too).

Researchers (Dr. Bernard Jasmin et al.) noted that in cases of depression, exercise can be similarly effective to first-line treatments such as medication and psychotherapy, but adherence is often lower and drop-out rates are higher than with antidepressants despite their side effects.

It’s not laziness, either; symptoms such as low energy, lack of motivation, and anhedonia—along with socio-economic pressures, co-morbidities, inexperience, time constraints, older age, stroke history, and functional limitations—can prevent people from starting or maintaining exercise.

You can learn more about this here, by the way: Laziness Is A Scooby-Doo Villain ← which means: to tackle it requires doing a Scooby-Doo unmasking. You know, when the mystery-solving gang has the “ghost” or “monster” tied to a chair, and they pull the mask off, to reveal that there was no ghost etc, and in fact it was a real estate scammer or somesuch. So it is with “laziness” too; there’s always something else underneath (e.g. the debilitating factors we mentioned in the previous paragraph)

Social psychologist Dr. Devon Price wrote about this (not with that metaphor though) in his book: Laziness Does Not Exist – by Dr. Devon Price

So the trick that Dr. Jasmin et al. went for is making use of muscle as a signalling organ that communicates with the brain.

This is because of the muscle–brain axis: skeletal muscle makes up approximately 40–50% of adult body mass and releases cehmicals collectively known as a myosecretome during contraction, which can reduce inflammation and increase neurotrophic factors that support brain health.

Sounds like a job for exercise mimetics!

What exercise mimetics are: exercise mimetics—which can be called “exercise pills”—are natural or synthetic compounds that activate key endurance-related signalling pathways in skeletal muscle, shifting fibres towards slower, more oxidative properties without physical training.

For example, compounds such as AICAR, GW501516, metformin, resveratrol, NAD+ boosters, and urolithin A, all of which may alter muscle metabolism and the composition of molecules released into the bloodstream. We wrote about several of these, by the way, in: Dr. Greger’s Anti-Aging Eight

Which can help a lot in this case too, as you can see in the paper itself: Exercise mimetics as unexplored therapeutics for treating depression

Want to learn more?

If you like this, then you’ll love the already-available…

Mediterranean Diet… In A Pill?

Take care!