Very simple Ozempic primer

Going long on the Rx drug's basics, its effectiveness, long term questions and drug-free alternatives

Normal groceries for a normal person

I read a lot about Ozempic but nowhere discusses what it’s actually about and why people really take it. Or how it works chemically for people who don’t have diabetes and how it works for people who have Type 2 diabetes and are in the drug’s prescription use case. This is naive—the chemical processes at work in each situation are different. But in media stories I have read about Oz, only the proper use case gets explained, and only the non-use case—non Type 2 diabetics—gets addressed as a phenomenon. Something’s missing. Instead of plain, tangible information with context and explanation there is moralizing, secrets, judgment… and scant info about the specifics of the drug.

To be sure, the field is changing. The shortage news—not enough Oz for diabetics; still the case now—exists in tandem with a sophisticated, advancing market where many off-brand Ozempic similars are available, effectively, without a prescription… so, more of the drug. Still, aside from a couple good pieces (this one in

Feed Me

was top), reportage has not caught up. Or maybe analysis hasn’t. Stories that report on the drug don’t take people’s… desire to use Ozempic to lose weight seriously. They are judgmental. The tone feels like the way in which people discussed plastic surgery 20 years ago: You’re one of them…?

Anyways, a few readers have asked me about Oz and so I am answering their most common questions below. Some from readers, some follow ups. My opinions on Oz and Rx drugs sit at the bottom of the letter. The context is: I get why anyone (straight up anyone) would use it.

Info below was collated from speaking to nutritionists, biochemists, reading stories, social posts from doctors, etc. and earlier interviews I did/reported on these topics for other publications. Later context about the rough mechanics of diets and groceries is included since Oz is really marketed to the non-use case population now, and the decision is about losing weight. I have even less of an opinion on that. Anyways the non-Rx stuff I mention has worked, and weight is the topic.

Vague language below denotes… the non-concrete nature of health inputs.

What is Ozempic and what does it do?

Ozempic is the brand name for semaglutide, a prescription drug approved in 2017 by the FDA which is prescribed to Type 2 diabetics, and which works, very roughly, by creating more insulin. The drug is a glucagon-like peptide-1 receptor agonist, which means it mimics the body’s hormone (the hormone is called GLP-1) that the pancreas secretes and which controls insulin secretion to the bloodstream. So: more GLP-1 means more insulin. The reason why it spurs weight loss is GLP-1 also sends a neural signal to the brain for satiety—it tells your brain you are full—and, roughly, also makes the stomach take longer to digest, and stay full with food longer.

Very roughly, people, both Type 2 diabetics and non, don’t feel as hungry when given a GLP-1 agonist, and don’t eat as much.

What is special about Oz. vs other GLP-1 drugs?

Ozempic or Wegovy (different brand name, higher dose version more or less) are different from previous diet drugs (Saxenda, Victoza) that were GLP-1 agonists because of their dosing. Hard to get more specifics about this even from doctors.

What is the connection between Type 2 diabetes and obesity?

It’s not 1-to-1, but, very quickly, digestion goes as follows: When food is ingested it then turns into glucose, and this glucose either goes into the blood (blood sugar) or into cells (digestion) and muscles (glycogen, stored); this is very, very rough. Diabetics do not have “proper” insulin secretion and so have too much sugar in their blood, which means not enough in the cells, and so diminished cellular function… as well as diminished satiety and so on, hunger… and they can become obese. Study findings have shown “too much” stored fat in the body in people without diabetes can lead to them developing type 2 diabetes… so the cause of diabetes often is this decreased cellular function and more blood sugar from, I suppose, lifestyle choices. Not being prescriptive here… if it sounds that way, forgive me…

How well does Oz work?

From studies? Quite well. The main GLP-1 study, (linked everywhere; prestigious journal), conducted on people without diabetes, was published in Nature, the scientific journal, in 2022. In the study, the cohort (mostly white women around the age of 47) lost 15% bodyweight, and kept it off. The weight was lost over a two-year period; a placebo group lost under 3 percent.

There is a new four-year study, billed as long term, also in Nature, from this year. I am pretty sure it’s the same cohort? Or at least it is still non-diabetics. The numbers there are as significant, but more reined in. Effectively—10% weight loss for the Oz group, sustained over 4 years, vs. 1.5% for the placebo. We can fisk the 5% dropoff and be critical here but the context is people don’t really ever keep the weight off (in studies) long-term. And so even rocking at 10% is an insane accomplishment.

Does it stop working after a while?

In the more recent study, most of the weight loss occurred in the first 39 months:

chart in second Nature study

And then stabilized. After that the weight mostly stayed off.

Anecdotally, there’s discussion that the drug stops working after a while. On a rough skim, “not working” actually means people have seen their weight loss… hold steady... taper off. As opposed to it coming back. Which tracks with the above data in the chart. Most of these people—again, not a real experiment but a skim of strangers on Reddit—lost most of their weight immediately and then kept it off after. Hard to say what would happen, say, over a decade of use. And—the studies above don’t give diet, BMI/Dexa, exercise particulars, and so on. To truly assess one of these studies (or even this drug) I would say you need 20,000 words.

What are the downsides?

The granular downside that jumped out to me (and others a couple years ago) is loss of bone density. Studies have shown that when people go on and stay on Ozempic their bones get less dense. Specifically, a meta-analysis (review of different studies) found bone density loss prevalent in a number of Oz studies they surveyed. It should be mentioned though that the meta analysis found no bone density loss on the lumbar spine, or whole body bone mineral density. Instead density loss was localized, to my understanding, to people’s hips.

This is at once tough to comment on (we don’t have many details involving the study cohorts here) and, in a Chad way, worrying since fragile bones… lead to, in starkest terms, a higher rate of mortality. (Basically if you are old and have fragile bones and fall it is the beginning of the end.) To be sure, while doctors like Howard Luks (who I interviewed about this), and Peter Attia (also talked to him) have sounded this alarm in their books, each say it’s very reversible. If you weight train (no shit; a few times a week) your bones become denser. It is kind of that simple.

Back to the issue at hand; dark nutrition people (Attia the most high profile) clocked the bone density drop-off two years ago and were very nihilistic about the long term effects of Oz.

But the criticism has since been walked back…. or matured, maybe, owing either to more studies (or more money)... or maybe just more use case There’s a JAMA study that found exercise can help stem bone loss in GLP-1 users—i.e. they are taking Attia’s advice. (There are anecdotal examples of this as well.)

I also talked to Bill Lagakos, a PhD in biochemistry, about the drug, about this. He explained to me the rapid loss in bone density in Oz users was likely due to their losing weight from the drug so quickly. As in… not intrinsic to the drug, but intrinsic to TIME—lose 15% of your bodyweight that quickly and you’ll lose lean muscle mass, too.

Is this one less thing to worry about or… noise? The unsatisfying and pat answer is that we will see in time. But it seems that the degree to which bones become less dense is… reversible, and finite.

Is it safe long-term?

Don’t ask me that—I don’t know you or your chart, and this isn’t health advice, and I only write for a newsletter. That said, a couple of ambient and contradicting ideas about Oz’s safety.. and indeed, any pill:

• One, it’s a pill—a new one. Get real. Who knows what side effects shake out from taking a pill for 10, 20 years.

• Two—you never know. There are 30-year studies of statins… which are heart drugs… and everyone on those isn’t exactly dropping like flies. These drugs get used for years. Maybe Oz is one of these drugs? Though typing that out makes me feel like the most naive bitch who ever lived…. I suppose there is also the pill (OCP), which has been prescribed to women for decades, with these women taking it for decades. Though there is, to put it mildly, a perception issue about the nature of the pill’s side effects.

Chad Math though says given a 10-year timeline, if you fix up your groceries you can improve on any results this drug delivers.

Does it work?

I mean, it’s a pill—but it seems to work insanely well for a year. So do some flash diets, and diet and exercise. But Oz is easier, has less friction and doesn’t require a lifestyle change or severe consistency.

Should I take it?

No way man I’m not answering that question.

What’s gonna happen in the next 20 years with this stuff?

Gonna be crazy. How I see this probably shaking out, with pill-mill varieties of GLP-1 available and marketed on the subway, and as rich people shit, is Oz/dupes being somewhere close to the pill (OCP): a drug many people take regularly and for a while, incorporating it into their lives, albeit with a real suite of real side effects… but one which, I don’t know, people live with. Or everyone takes it and works out more and nothing happens. Or every long-term user not in the Type 2 diabetes use case develops osteoporosis and serious vitamin and nutrient deficiencies or rickets/scurvy or something from going hypocaloric and never being hungry. Or some surprise factor comes up in a year or two and changes everything. Not a satisfying answer but it’ll be one of the above.

Are you worried?

For the most part, I think individuals have a more nuanced and capable understanding of how Oz and other Rx drugs work than can be expressed in a series of narrative sentences… whether news stories or legislation. Medical consumers (a group that comprises most people) are very smart and there is some doctoral-level economic math that goes into normal people’s decisions about whether to buy a certain drug and/or stay on it. When shit gets too dangerous, if it does, people will figure out how to jump ship. I hope. Or maybe I just don’t want to be concretely negative. Who can know.

What is as curious to me is how such an effective pill will change people’s… health regimens. Will it change how people exercise? (If you eat much less you will lift less.) Move through the day? What people eat? (Will people just only eat liver and kimchi or something?) So many variables.

That’s it for the big questions about Ozempic. Below, some context of how it relates to weight loss and metabolic syndrome in general.

Sami Reiss (left) after two beers

You mentioned groceries? Come on. This is science—how do groceries weigh in here?

Bear with me. This is a bit shaky. But America is 40% pre-diabetic—defined as higher than normal blood sugar levels that, without a lifestyle change, will prob. lead to Type 2 diabetes—and the dark nutrition argument is this is from groceries. It can’t really be explained in an article or in studies (it’s not airtight)… but… well, I don’t know. I believe it. Reacting to this system in different vague ways is what “dark nutrition” is about.

Specifically, these influencers say that “processed foods,” and more specifically vegetable oils, have shredded people’s digestive systems and metabolisms (good rundown here; podcast with notes and critique). The argument kind of makes sense: veg oils are everywhere (in most groceries), and are new additions to people’s diets, evolutionarily speaking (only a century old)…

Quick/definitive ways to avoid seed oils at restaurants

But there is no real smoking gun/airtight study that veg. oils are bad bad bad. At best, bad for gut health and satiety, and inflammation, and they are “processed.” People can also read these studies charitably and come to the conclusion that daily usage can also harm cells at the mitochondrial level. (I believe this.) But if truth and definitions are academic, the reality of groceries is much more lenient. We all eat and buy groceries every day. If we don’t keep our refrigerators full, then we buy other food every day. And so, very quickly, it’s fine to be very skeptical about whether decades-old food ingredients are safe for decades-long use. These aren’t vegetables, you don’t have to eat them.

So buy other food?

Well, it is widespread. What I mean is, try buying normal food at a gas station. People have to choose but it’s so widespread that it can affect choice. And yeah, of course there is healthy food out there—in places where people have cash. But in many places there just kind of isn’t. And the conclusion here is that it makes sense insulin resistance, pre-diabetes, metabolic syndrome, other things… all the direct use cases for Oz (and ones that are precursors for Type 2 diabetes) are a feature of this system, if good groceries are the minority of what gets sold to food consumers.

More Chad Math: if 80% of the grocery store’s full of poison then it would make sense 40% of America is pre-diabetic.

And so course people would want and need to take Ozempic. And not in, like, some patronizing way. It just makes sense, as a rational decision assessment in this marketplace.

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OK, but groceries?

Yeah, the solution happens to be groceries. It’s crazy. It really just is normal groceries. Like old people food. You can get specific and fine-tune them or you can just buy food that does not come in a box… this variance has to do with your aesthetic goals, how “skinny” you want to look.

Out of respect for this topic I’m not paywalling anything here. Red meat, eggs, root vegetables, simple carbs, fermenteds, fruits and fruity veggies (cucumbers, tomatoes), cheeses, and so on. A bit less of some, if you are “cutting.” And with movement and exercise. Of course, details vary, and we all have blindspots, and so it’s good usually to chat with someone—just to get gut-checked—but over a decade any person with interest and half a brain will be able to lock it in. That said, the difference between this protocol and Ozempic is that you need to do it every day forever. But it is good.

I should mention I don’t like listing out food choices before the paywall (it is prescriptive and judgmental)—but I am quite stringent and direct after the paywall. (If you pay money then you’re a big boy and can handle the truth.) Again, I don’t have any opinion about how other people in America eat. It’s more that such a grocery protocol, conservatively, doesn’t really have a downside, and might work.

What should I eat on Ozempic?

Not really gonna answer that, but if it was me I’d probably eat lots of tripe and other nutrient dense foods, make your tiny appetite count. But yeah, no way.

What are other ways to manage appetite without Oz?

With the caveat that you should not give a shit about body image all the time (now and then is normal)…. lest you get body image issues—prevalent among lifters, check out this Iron Culture pod ep for a longer discussion—the… old school answer is you should:

Deal with it. If you cut, if you decided you want to lose weight, if you are going after this specific aesthetic goal—you’re going to be a little hungry. You’re going to have to rein it in some of the time. Or be more active. Or something. Maybe not all the time—definitely not all the time—and you don’t have to ruin your relationship to food. But it’s not a party. (Even Karl Lagerfeld* understood this.) That’s the behavioral science of food for people with aesthetic goals. Having muscle or a looser goal can allow for more leniency.

That said, any competent diet—or, better said, long-term way of eating with some or many boundaries—defines itself by how it manages hunger. That’s what all diets do. The best ones minimize it greatly.

*The best diet book ever written. Everything in this book is true. It is a hinge between worlds.

Why are diets bound around hunger management?

Very simply, so once can be below their caloric requirement* and therefore lose weight, but not be so hungry that the diet is painful and they’ll quit it. This is why so many influencers/doctors promote the same vague ideas—protein, real foods, walking. Protein especially: it’s required in a normal amount to keep muscles around, so you can slowly raise your metabolism (more muscles=need more food).

*Calories are mostly true, and in many ways not, but for aesthetic goals they are pretty true.

Traditional Sami Reiss dinner; protein source replaced with can of delicious primer

Examples of how “diets” manage hunger:

• Volumetric eating—foods like chicken thighs, white potatoes, watermelons, lean beef… foods that take up a lot of space on a per calorie basis (opposite foods: almond butter, trail mix, etc.)

• More protein—protein tends to be more filling per calorie compared to carbs and fats. And many people, if they don’t “track” their protein, do not get “enough.” And so eating more of it helps you feel full and prevents your muscles from catabolizing (fancy word for disappearing).

• Avoiding “fake foods”—the dark nutrition argument is if you avoid seed oils you don’t need to count calories. Mostly true but non-disprovable, but what is true is these foods have satiation limits (i.e. red meat has fat and protein, fruits have fiber); eating this way without boundaries may not lead to specific aesthetics, though, but if you’re active and jacked and do it for long enough it prob. will

• Protein junk foods—opposite of the above. This explains the market behind protein chips, powders, bars, Fairlife milk and so on. High protein foods that are tasty and which have emulsifiers/etc and which help people hit their cal goals. The fascinating thing about nutrition and what makes it difficult (and fun) to write about is that both this and the real food arguments… lead to real results. Both are completely and simultaneously true. They just are. Both work for a while. Often for the same person. Just how it is.

• Fasting—almost counterintuitive, but gating hunger to part of the day is “better” than being pesky hungry after a shitty/too-small calorically meal. The hunger at the end of a fast is less… aggravating. Fasting is all right though less ideal long-term; post in the works about that.

So groceries are the answer?

Yeah over a decade for sure, but come on. Anyone who’s ever tried to cut weight knows that it sucks. It stinks. Maybe only a little bit, but it does. Or, rather, it involves effort. It’s not frictionless. I have tried all of the above protocols (and others) since I started working out when I was in high school, and tracking protein in college, and the best, to me, is single-ingredient foods. But even then, it took a while until I locked it down. Ozempic… I don’t know, it works in the short term. Hard to argue against that. But, gun to my head… the actual answer, honestly, is eating 14 eggs a day, every day, and grazing now and then, whenever you want, with foods that don’t come in a box. If you like, if you are aesthetically inclined.

Really, a dozen eggs?

Yeah. Pasture raised. Eat 14 eggs a day for a year and do 50 push-ups every other day. For a year. Gender non-specific.

Why eggs?

They are swag. More specifically, they are the most bioavailable protein and have lots of nutrients. You will need to eat other things to balance it out. But it diminishes them (and food in general) to speak of them in purely scientific and nutritional terms. That said I wouldn’t do this for more than 7 years.

Isn’t it dangerous to limit your long-term diet so drastically?

You tell me.

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My actual real 2c on Rx drugs and Ozempic: pretty Chad: the more prescription drugs you take, the more variables there are in your life, and the less… space you have for an Rx drug you might need need. I reached this POV from when I was on a bunch for a while after my spinal surgery, and they turned my life upside down. I would say that the Rx drugs in fact were worse than the surgery. As far as Ozempic, well, some people need it for sure. Truly no opinion on people with Type 2 taking it. And not really about anyone else. More than that, it is an incredible technical accomplishment and it for sure works better and quicker than (ALMOST ALL) diets in the short term. I would probably use it if I was over 40% body fat and then try and get off it as soon as I can. It’s not a death sentence but IDK, using it for more than a year, I would avoid that. Not advice whatsoever but wanted to be clear about where I am coming from to take the above in context. And when I say almost all diets, there are like two or three that work really well and which are safe and so on and which shed an insane amount of weight… subject of upcoming newsletter.