I was having a conversation with a member a few weeks ago about what they should tell a relative who is considering one of the common drugs currently being prescribed for weight loss. I had assembled some podcast episodes of people whose information I trust on the matter (Peter Attia, Renaissance Periodization). This post is an attempt to consolidate some of the information from those episodes.
One thing to note. I’m not a doctor, or a scientist, just a dude playing the part of a humble bro-scientist trying to assimilate the best information I’ve heard on the topic. As always, if you have any questions about what’s right for you…talk to your doctor.
You’ve undoubtedly heard about Ozempic, Wegovy, Mounjaro, or—the one with my favorite name—Zepbound. These drugs are part of the GLP-1 Receptor Agonist (GLP1RA) class, originally created for diabetes management to help the body produce more insulin. But then they noticed an interesting side effect—weight loss. So, are they any good? Let’s explore the pros and cons.
How Do They Work?
The GLP1RA drugs were initially created to help the body produce more insulin, making them ideal for diabetes management. However, they also mimic the Glucagon-Like Peptide-1 (GLP1) hormone, which is naturally released from the GI tract. This hormone sends a signal to your brain that you’re full, and it slows down your digestive system, further enhancing that feeling of fullness.
All of these mechanisms help people feel less hungry, resulting in fewer calories consumed. As we discussed in a previous blog post, to achieve a certain weight, you need to eat the maintenance calories for that body weight—around 12-15 calories per pound. By taking these drugs, people more easily consume the number of calories appropriate for a lower body weight, leading to weight loss.
Does This Work for Everybody?
So far, GLP1RAs have proven to be one of the most effective ways for people to lose weight—short of being in a nutrition lab where every calorie is monitored (something almost nobody has access to). Studies indicate that about 85-90% of people lose more than 5% of their body weight with these drugs, which is highly successful, especially from a population level.
It’s worth noting that newer variants of these drugs tend to be more successful than older ones. However, drug companies’ trials and other studies have shown that the weight loss is generally only maintained while taking the drug. For example, in a study linked here, participants who took the drug for 68 weeks lost nearly 20% of their body weight, but they regained about two-thirds of that weight over the next 52 weeks after stopping the drug.
The takeaway? If you want to use a GLP1RA as a one-and-done weight loss solution, you’ll still need to make lifestyle changes—diet and exercise—if you don’t want to be on the drug forever.
Are There Side Effects?
To quote the famed economist Thomas Sowell, “there are no solutions, only trade-offs.” There are clear health benefits to losing excess body fat, whether it’s through monitoring calorie intake and exercise or using a GLP1RA; however, these benefits can come with a cost for some people.
Around 50% of people report nausea while on the drug. In a podcast, Yuval Noah Harari details his experience losing 40 pounds with Ozempic, in part because the nausea made eating less appealing. Approximately 10% experience nausea and diarrhea, and anywhere from 1-10% experience vomiting and abdominal pain.
The good news is that most side effects tend to be most pronounced at the beginning of treatment and often subside over time. Still, as Milton Friedman once said, “there is no such thing as a free lunch.” You’ll need to weigh these side effects against the reduced risks from serious complications of obesity.
Availability
Given the number of people looking to go on a GLP1RA drug, there is significantly more demand than supply. This scarcity is one reason these drugs are so expensive.
One little-known fact is that the FDA allows compound pharmacies to replicate the drug if demand exceeds the patent holder’s ability to produce it. When you see commercials for generic “Semaglutide,” you’re probably seeing a compounded version, which may not be identical to Ozempic. While I haven’t heard of significant issues with these versions, it’s something to keep in mind if some sketchy guy in a dark alley is offering you a vial of Mounjaro.
What Don’t We Know Yet?
A valid critique of GLP1RAs for weight loss is the lack of long-term data. Since these drugs have only recently been used for weight loss, we don’t yet have long-term safety data for this purpose. However, GLP1RAs have been used by diabetes patients since 2005, and long-term studies for diabetes have shown that the benefits generally outweigh the risks.
If the risk/reward ratio for weight loss is anything like it is for diabetes management, I suspect the long-term trade-off will be worth it.
But…Isn’t It Cheating?
In my humble opinion… no, it’s not cheating.
For around 200,000 years, humans have existed in a world where food scarcity was the norm. Our bodies became ruthlessly effective at conserving energy in the form of fat. Only in the last 50 years or so have we seen food become calorie-dense, hyper-palatable (a.k.a. extremely tasty!), widely available, and relatively cheap. At the same time, sedentary jobs and screen-based entertainment mean we’re also moving a lot less.
This is known as the evolutionary mismatch hypothesis—traits that helped us survive now work against us in today’s environment. It’s not that we suddenly lost our willpower; the environment has changed. GLP1RAs are simply technological advancements that help us level the playing field.
But Don’t You Own a Gym? Aren’t You Afraid You Won’t Be Needed?
Not at all. I always explain to people that while the workouts they do in the gym will help with weight loss, exercise alone is not sufficient—calorie restriction must be part of the strategy. GLP1RA drugs are simply another tool we can use to maintain a calorie deficit and lose weight.
One of the most common hesitations I hear is, “I’m not in shape enough to do what you people do.” I believe that as people lose weight, they’ll become more active because moving won’t feel as hard. Plus, while GLP1RAs can help you lose body fat, they won’t help you build muscle or get stronger.
So, if you want to look better in your clothes, losing fat will help. But if you want to look better at the beach, that’s where we come in! 😏
The Takeaway
The GLP1RA drugs are not a silver bullet. They can provide significant benefits, but not without costs. Can they be useful? Of course, but they don’t eliminate the need for lifestyle changes like diet and exercise. At the same time, these drugs come with risks that must be carefully considered with your healthcare professional!
