Ozempic and friends: miracle drug or big pharma quackery?

Issue #72: Ozempic and friends: miracle drug or pharma quackery?

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Read Time: 7 minutes

Good morning, 66.1ers.

A new approach to this Saturday's newsletter.

This is the first of 4 issues coming your way over the next month that will go deep on one issue.
After those 4 issues are published, I plan to move the deep dives (and a few other new features) over to a paid subscription.

If you prefer the other format (brief, skim-friendly) I've been writing, don't worry.
That will be back in your inbox on Wednesday.
And it will always be free of charge.

In this week's issue of 66.1:

A deep dive into Ozempic, Wegovy, and other semaglutide drugs used to treat obesity and overweight.
If you're not worried about your weight, I encourage you to look into the article anyway.
There are some serious findings about how pharmaceutical interests are undermining the integrity of science.

A quick refresher for anyone who's new to the newsletter: 66.1 is the average health span (years lived without a serious disease) in the US. We're here to extend that.

Background

According to the CDC, 74% of adults in the US are overweight or obese. And it’s well documented that overweight and obesity are associated with a host of other chronic diseases like cancer, type 2 diabetes, and heart disease.

Ozempic was first approved as a treatment for type 2 diabetes by the FDA in 2017. Ozempic itself is still not approved for weight loss treatment, but drugs of the same class have been approved. Most popular among these drugs that are approved for weight loss is Wegovy.

After decades upon decades of searching for a “miracle drug” for weight loss, it seems that we’re closing in on one, especially if you consider the results published in this journal article in the New England Journal of Medicine (NEJM), which found that a once-weekly injection of semaglutide at a dose of 2.4 mg yielded a mean decrease in body weight of 14.9%.

That sounds darn close to a miracle, especially if you’ve been struggling for decades to lose weight.

Before we go singing the praises of semaglutide as the silver bullet for weight loss, though, let’s dive a little deeper.

How it works

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. In lay terms, it mimics GLP-1. This mimicry makes you feel full. Semaglutide activates the GLP-1 receptors in the brain, reducing feelings of hunger and reducing calorie intake.

It also delays gastric emptying, the process through which food leaves the stomach and enters the small intestine. Again, this delay prolongs feelings of fullness and satiety, further reducing food intake.

Finally, semaglutide has been shown to increase energy expenditure and promote fat burning, which can lead to reductions in body weight and improvements in body composition.

This information is paraphrased from this article from the Mayo Clinic.

Does it help with weight loss?

The NEJM-published study yielded dramatically positive results for a semaglutide intervention.

A few points worth noting:

1. Participants received the injection weekly for 68 weeks
   If you’re counting, that’s a year and 4 months.
   Not an overnight miracle drug, if that’s what you’re looking for.
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2. The pharmacological intervention was paired with a lifestyle intervention (calorie-restricted diet, exercise, counseling sessions).
   The control group received either a placebo injection and the lifestyle intervention or just the lifestyle intervention.
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3. Participants receiving the semaglutide intervention lost dramatically more weight than participants on only the lifestyle intervention.
   14.9% reduction vs 2.4% reduction, to be exact.
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4. Overall body composition: for participants in the semaglutide group, total lean body mass decreased in absolute terms (in kg), while the proportion of lean body mass relative to total body mass increased.
   ​
   In simple terms, they lost weight, but not all of it was fat.
   Muscle was lost as well.
   Not ideal, but a sacrifice that may be worth making for the cascade of positive health effects that can occur from simply getting down to a weight that allows you to be more active.

So far, it seems that semaglutide has positive effects for weight loss, at least over the course of this 68-week intervention.

Before we get too excited, though, there’s one more study we need to examine.

Will you be able to keep the weight off?

This study examined how participants in the first study fared after their 68-week intervention was up.

Notably, all interventions (both the semaglutide injection and the lifestyle intervention) were stopped at this point. For the placebo group, the lifestyle intervention was stopped.

Following treatment, semaglutide recipients in this study had lost a mean of 17% of their body weight. Placebo participants had lost 2.0%. After halting the treatments, semaglutide participants regained 11.6% of their original body weight and placebo participants regained 1.9%. In short, both groups regained most of the weight they had lost. This measure was taken 52 weeks after ending the intervention, at week 120.

While the authors of the paper suggest that this trend is evidence for the chronicity of obesity and overweight and necessitates ongoing treatment (implying ongoing treatment with semaglutide), I wonder if perhaps something is being overlooked. Importantly, the study on weight regain discontinued both the semaglutide injection and the lifestyle intervention after week 68.

People who were being coached to exercise more, eat cleaner, and sleep better suddenly had all this support removed from their lives.

Of course they regained the weight!

A more common-sense study might have removed the semaglutide injection after 68 weeks and maintained the lifestyle intervention for a number of months.

It’s asinine to believe that you’ll maintain weight loss if you go back to eating a calorie surplus, not exercising, and sleeping poorly.

Had the lifestyle intervention been maintained, I have a hunch we would have seen different results. And it’s quite disappointing, frankly. Because we’re peddling the narrative that obesity and overweight are immutable diseases afflicting more than 70% of the American public, and the only thing to do about them is to take medication for the rest of your life.

A conflict of interest

This whole deal sounded a little off to me. So I looked into the authors of the paper. John Wilding, the lead author, is a researcher at the University of Liverpool whose work is focused on Obesity, Diabetes, and Endocrinology. To his credit, he shares a “Declaration of Interests” on his profile on the World Obesity page.

You don’t have to read far into this declaration to learn that he has financial ties to pharmaceutical companies, including Novo Nordisk, the manufacturer of Ozempic and Wegovy and sponsor of multiple clinical trials conducted by Dr. Wilding.

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Applying it to your life

Now, I’m not here to start a conspiracy theory.

And I’ve got no interest in becoming an investigative journalist.

I just want you to be able to dance at your granddaughter’s wedding, throw the football with your son, and live your life without prescriptions.

With that goal in mind, let’s get to what to do with all this information.

After spending the early morning hours of every day this week reading about Ozempic and related drugs for weight loss, I’ve reached a conclusion that surprises even myself.

It seems that using semaglutide can be a powerful way to accelerate your weight loss. It’s a tool worth using, but it’s important to deploy it strategically. Because, at the end of the day, weight loss requires more than an injection.

It’s about lifestyle interventions–eating at a calorie deficit, moving more, sleeping better–sustained over years and decades.

So, yes, the authors were right. Ongoing treatment is required to maintain weight loss. If you need a jump start because the problem is out of control, semaglutide might be a valuable tool. That’s a question for your doctor. But the real ongoing treatment is putting the right food in your mouth, moving your body, and getting your 8 (or so) hours every night.

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That’s all for this Saturday.
​Before you go, I have a favor to ask:

Send a reply here and let me know what you thought of this one.
Worth continuing to write deep dives like these and publishing 2x/week?

See you on Wednesday with our classic newsletter format.

Have fun out there.

Marcus​
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Why 66.1?
​66.1 is the average health span (years lived without a serious disease) in the US, as of the start of this newsletter publication.
​We're here to extend that.

​