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Good morning, 66.1ers.
Welcome to issue #117 of 66.1.

Housekeeping

Full access to this post and podcast is reserved for paid members of 66.1.

Free subscribers: if you want to hear my thoughts on:

• The latest science about GLP-1 drugs and their effect on 175 different health markers

• The risks and benefits of using a GLP-1 drug to lose weight

• My take on using GLP-1s (and who might benefit from using them)

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Today’s issue brought to you by Freedom Fats

Setting the scene

I first wrote about GLP-1 drugs (Ozempic, Wegovy, Mounjaro) back in November. That piece was equal parts exposé of perverse pharmaceutical industry and analysis of the benefits of GLP-1s for weight loss.

Given the demand for weight loss solutions, use of this drug class continues to proliferate and scientific papers are abundant. Interestingly, recent studies have shown that GLP-1s have an effect on health outcomes extending well beyond weight loss or Type 2 Diabetes management (the original use case).

The scientists mapped 1,955,135 individuals for a median of 3.68 years. They mapped the associations between GLP-1RA use and 175 health outcomes during this time.

Before we dive in to the study in question, it’s worth a refresher on how GLP-1s work. Don’t try to memorize this—just use it as a reference when questions come up.

4 takeaways

• GLP-1s can help with a wide array of conditions: most improved under GLP-1 treatment were cardiac arrest, hepatic (liver) failure, and even Alzheimer’s Disease

• The science isn’t unbiased: two of the authors are “uncompensated consultants” for Pfizer, which is researching its own GLP-1 drug.
  Side note: 92.6% of “unpaid/uncompensated consultants” are associated with for-profit companies.

  

• GLP-1s mess with your digestive system: of all the body systems, the digestive system was most negatively affected by GLP-1 treatment

• It’s hard to tell…do these positive effects happen because of the GLP-1 treatment itself, or because of the weight lost due to GLP-1 treatment?
  Put another way, if a person lost the same amount of weight (10-30% weight loss from baseline) without a GLP-1, would they see all the same benefits?

I could go on, but it’s probably time to look at the results yourself. Everything in blue improved when subjects were on GLP-1s. Everything in orange worsened. The hash mark in the middle is the starting point.

My take

As with any decision in life, taking a GLP-1 medication to manage your weight comes with tradeoffs. Ultimately, it’s up to you and your doctor to decide if these tradeoffs make sense given your current health scenario.

If you struggle greatly with weight (obesity, not wishing you had your beach body ready to go), it’s worth considering a GLP-1. The risks associated with having a body mass index (BMI) greater than 30 kg/m^2 are spooky:

• 5% increase in risk for atrial fibrillation (irregular heartbeat) for each unit increase in BMI after 30 kg/m^2

• 70% of obese individuals have unhealthy cholesterol levels

• 30% increase in coronary artery disease (CAD—call it disease of your heart vessels, in layperson’s terms) for each 5-unit increment increase in BMI

We don’t want to mess with these risks. The fact that there’s a drug that can help reduce the condition which puts you at risk for all these other conditions is a a bit of a miracle, an option to be seriously considered.

Now—and this is important—this evidence indicates to me that there are a couple groups of people who ought to steer clear of GLP-1s:

1. Anyone whose major health challenge is made worse by GLP-1s

   Hypotension (low blood pressure), GERD (acid reflux), and sleep disturbance are just a few of the conditions made worse by GLP-1s.
   If you have these, it’s more likely that the benefits of using GLP-1s do not outweigh the risks.

2. Anyone considering GLP-1s for minor weight loss

   If you’re 10 pounds from your goal weight, just stay on the path. No need to risk the potential increase in symptoms outlined above. Not to mention the fact that leveraging behavior change to lose the rest of the weight is going to have much more staying power.

At the end of the day, GLP-1s are a great tool to help take you from morbidly obese to a healthy weight. But, as mentioned in the first 66.1 issue about GLP-1s, it’s critically important you’re losing the right kind of weight.

If you go the GLP-1 route, make sure you’re maintaining a training routine and you’re eating plenty of protein (so your body doesn’t start shedding muscle mass instead of fat).

Put another way: "If you're taking these drugs, really, really pay attention to your protein consumption and your resistance training. . .that's obviously going to be an important part of being on the right side of that body composition curve.” 
— Peter Attia

As always, this is your weekly reminder that I’m not a doctor. This does not constitute medical advice—it’s merely the informed opinion of a trained health coach who’s spent the last 3.5 years working directly with chronically ill patients.

That’s all for this week.
Have fun out there.

Marcus