It’s fairly well-known that if you take a GLP-1 receptor agonist drug (like Ozempic, Wegovy, Mounjaro etc) for weight loss and then stop, the weight will return.

See for example: What happens when I stop taking a drug like Ozempic or Mounjaro?

This is important to consider, as it means that starting to take a GLP-1 RA drug is something one should be prepared to then continue doing for the rest of one’s life, if one wants to keep the weight off.

There are, of course, a lot of people who go onto GLP-1 RAs with the rationale “I’ll just use this to lose the weight, and then I’ll keep the weight off with my diet and lifestyle”.

Which sounds reasonable, but because of the specific mechanisms of actions of GLP-1 RAs, it simply doesn’t work that way (indeed, there are even reasons that you may, after stopping taking GLP-1 RAs, be more disposed to put weight on than you were before you started*). So, by the best of current science (which admittedly is not amazing when it comes to this topic), it does seem that taking GLP-1 RAs is a lifetime commitment.

You can read more about this here: Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity

*We wrote previously about how a person who has been on GLP-1 RAs may afterwards be even more inclined to put on fat than before:

❝Of the four studies that actually looked at the macros (unlike most studies), they found that on average, protein intake decreased by 17.1%. Which is a big deal!

It’s an especially big deal, because while protein’s obviously important for everyone, it’s especially important for anyone trying to lose weight, because muscle mass is a major factor in metabolic base rate—which in turn is much important for fat loss/maintenance than exercise, when it comes to how many calories we burn by simply existing.

A reasonable hypothesis, therefore, is that one of the numerous reasons people who quit GLP-1 agonists immediately put fat back on, is because they probably lost muscle mass in amongst their weight loss, meaning that their metabolic base rate will have decreased, meaning that they end up more disposed to put on fat than before.

And, that’s just a hypothesis and it’s a hypothesis based on very few studies, so it’s not something to necessarily take as any kind of definitive proof of anything, but it is to say—as the researchers of this review do loudly say—more research needs to be done into this, because this has been a major gap in research so far!❞

Read in full: Semaglutide’s Surprisingly Unexamined Effects

So, what about short-term interruptions?

We like to bring you hot-off-the-press science news, in this case, it’s so new that the paper in question hasn’t actually been published yet.

However, a press release was made at the Endocrine Society’s annual meeting—yesterday, at time of writing.

The good news: they found that GLP-1 medications like semaglutide and tirzepatide remain effective for weight loss even when access is disrupted.

The bad news: it’s not like the disruption didn’t have a negative impact, though; weight loss was also temporarily disrupted; temporary partial weight regain was a relevant factor (just, weight regained was then lost again upon continuing)

In numbers: 6,392 participants in a metabolic health program were tracked over at least one year; the program combined GLP-1 RA treatment with lifestyle changes in food, exercise, sleep, and emotional health, plus one-on-one coaching. Of those, 72.5% of participants experienced at least one GLP-1 access disruption; 11.1% had multiple. Here’s how much difference that made:

• Without access disruptions: 17% average weight loss at 12 months, 20.1% at 24 months.
• With access disruptions: 13.7% average weight loss at 12 months, 14.9% at 24 months.
• With only 1–4 treatments in 12 months: >10% average weight loss at 12 months, no data for 24 months (in all likelihood they regained the weight as is normal, but the data was not recorded so we can’t say that for sure)

While we can’t link to the paper that hasn’t been published yet, we can link to the press release: Study finds patients with interrupted GLP-1 access still achieve significant weight loss

All of which points to the idea that “some is still better than none” when it comes to drug availability, and that one probably shouldn’t become overly stressed about missing a dose (for example, due to supply problems, cost issues, bureaucratic hold-ups on a repeat prescription, that kind of thing).

Nevertheless, that doesn’t mean things will necessarily be easy, for example:

❝Now that I am no longer taking the drug, unfortunately, my weight is returning to what it used to be. It felt effortless losing weight while on the trial, but now it has gone back to feeling like a constant battle with food. I hope that, if the drug can be approved for people like me, my [doctor] will be able to prescribe the drug for me in the future.❞

~ Jan, a trial participant at UCLH

Source: Gamechanger drug for treating obesity cuts body weight by 20% ← University College London Hospitals (NHS)

Want to maximize your chances of good results?

First, you might want to make sure you’re on the best GLP-1 RA for you, and that’s probably going to change over time as new drugs are developed and rolled out.

We wrote about that here: Better Than Ozempic? ← which finds that tirzepatide is better than semaglutide, retraglutide is better than tirzepatide, and an as yet unnamed tetra-receptor agonist drug is better than retraglutide.

You can also improve your results whichever drug you’re on, by bearing in mind: 10 Mistakes To Sabotage Your Ozempic Progress

Want a more natural approach?

It is possible to get many of the effects of GLP-1 RAs without taking GLP-1RAs, 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!

You can also check out: Ozempic vs Five Natural Supplements

Enjoy!

Spoiler: it’s good

What dreams may come, when we have shuffled off this deoxyribonucleic coil,

…must indeed give us pause!

Researchers (Dr. Umaimah Zanif et al.) did a randomized, placebo-controlled trial of 40 night-shift workers tested whether taking 3mg of melatonin daily for 4 weeks before daytime sleep (because: night-shift workers) could improve the body’s ability to repair oxidative DNA damage.

Why Dr. Zanif and her team investigated melatonin: melatonin normally rises at night and helps regulate sleep and circadian rhythms, but overnight work suppresses melatonin production, which can reduce the body’s capacity to repair oxidative DNA damage, and could be one mechanism linking long-term night-shift work to a higher cancer risk.

Quick note about the participants: all workers had performed at least two consecutive night shifts per week for at least 6 months, with shifts lasting at least 7 hours, and none had sleep disorders or major chronic illnesses.

Of course, that’s not to say it’s only night workers who are affected—it’s relevant for anyone with disrupted sleep. But night workers make for a clear, consistent demographic in which to study these matters.

You may be wondering how DNA repair was measured: the team measured urinary 8-hydroxy-2′-deoxyguanosine (8-OH-dG), a marker of oxidative DNA damage repair capacity, with higher levels interpreted as greater DNA repair activity.

The results, in numbers:

• Main finding: during daytime sleep after night-shift work, the melatonin group showed approximately 1.8 times higher urinary 8-OH-dG levels than the placebo group, suggesting improved oxidative DNA repair capacity.
• Statistical analysis: the increase was described as borderline statistically significant, with a 95% confidence interval of 1.0 to 3.2 and a p-value of 0.06.
• One more thing: no significant difference between groups was observed during the subsequent overnight work period, suggesting the benefit occurred specifically during sleep rather than throughout the entire day.

In other words, restoring melatonin signaling can counter some of the biological stress caused by circadian disruption in general and night work as a top-tier example of that.

You can read the paper in full, here: Melatonin supplementation and oxidative DNA damage repair capacity among night shift workers: a randomised placebo-controlled trial

We’ve also written a bit about melatonin before, including:

• Melatonin: A Safe, Natural Sleep Aid?
• Melatonin Supplementation & Your Heart
• Melatonin vs Lupus!

Want more options?

Some sleep aids can help, but many are harmful and/or do not really work as such; here’s a rundown of examples of those: Safe Effective Sleep Aids For Seniors?

Want to learn more?

For a much more in-depth treatment of the topic of sleep in general, you might like this book that we reviewed a while back:

Why We Sleep – by Dr Matthew Walker

Basically, if you will read only one book on sleep, that’s the book.

Sweet dreams!