Ozempic and Wegovy: All You Need To Know (Patreon)

[This is a transcript with links to references.]

In 2021, the US Food and Drug Administration approved wegovy a drug with the active ingredient semaglutide that helps people lose weight. In contrast to pretty much all previous weight-loss drugs, this one actually works. And it’s taken the world by storm.

According to Komodo Health, the number of prescriptions for this and similar drugs for weight-loss purposes has increased over two thousand percent from 2019 to 2022 in the USA. The demand is so high that Wegovy is now on the FDA’s Drug Shortages list. But it’s not just the US. Shortages have also occurred in the UK, Ireland, Canada, China, Belgium, and several other countries.

In Hollywood, everyone is now accusing everyone else of taking it while denying themselves they would ever touch it. And Elon Musk announced on Twitter that semaglutide helped him lose 30 pounds. At least I guess that “lbs” was supposed to mean pounds and not pounds per second. He’s also let the world know that it gave him next-level burbs.

Burbs aside, it seems to be a god-sent solution for everyone who’s been struggling to lose weight, a miracle cure for a problem that befalls billions of people. But what is semaglutide? What do we know about it? And who’s going to pay for it? That’s what we’ll talk about today.

Semaglutide, used for the weight-loss drug Wegovy, is the same active ingredient as in Ozempic, a drug used to treat type-2 diabetes. The difference between the two is that Wegovy has a higher dose. Both drugs are produced by the Danish company Novo Nordisk.

Semaglutide is a molecule that resembles a glucagon-like peptide, known as GLP-1, which the body produces naturally. GLP-1 is a hormone that’s released in the gastrointestinal tract in response to eating and which then sends signals to other parts of the body.

In the pancreas, GLP-1 triggers the production of insulin, which reduces blood sugar levels. Semaglutide does the same thing and that’s why it’s good to treat diabetes. It’s not the only molecule that mimics these GLPs, there are a few others. I can tell from my glance at the scientific literature that their effects are subtly different but, in all honesty, if I met a few of them on the street I probably couldn’t tell them apart.

Semaglutide has been studied for the treatment of diabetes for more than a decade and Ozempic was approved in 2017. However, already the first trials showed that one of the side effects of this and similar drugs was weight loss. Not an intended effect, but not an unwanted one either.

This is why Ozempic had a wide-spread use as an off-label prescription for weight loss for years. Eventually, Novo Nordisk decided to produce a drug especially meant for weight-loss. That’s the Wegovy that I mentioned in the introduction. It was approved as a treatment for obesity in the USA in 2021 and in the EU in 2022. It’s not just about the weight. The weight loss on semaglutide is accompanied by improvements in cardiovascular health.

Just exactly how semaglutide works is still subject of research, but it seems that the stomach also has receptors for the hormone GLP-1, and semaglutide can latch onto the same receptors. This slows down the emptying of the stomach, so you feel full for a longer time. GLP-1 also seems to act in the brain, where it reduces hunger, and again, semaglutide can do this too. Basically, semaglutide makes it easier to reduce food intake.

These drugs are currently available as a liquid that comes in a prefilled pen. You inject them once a week under the skin of the upper arm, thigh, or belly, if you have one. You start with a low dose and increase it gradually.

Semaglutide also comes in the form of pills. The reason there aren’t more people taking it is probably that it’s somewhat cumbersome to use. You have to take it daily with a certain amount of water on an empty stomach and then wait 30 minutes before eating. Moreover, some studies have found that the weight loss is substantially less. Though a very recent study reports that taking a higher dose orally produces a weight loss similar to that from injections, so maybe people are going to switch to those pills in the near future.

How well does it work? A 2021 study by an international team related to Novo Nordisk reported the results of a double-blind trial. They recruited almost 2,000 adults with a body-mass index of 30 or higher who did not have diabetes.

The participants received 68 weeks of treatment with a once-weekly injection of either semaglutide or a placebo. In addition to this, they faced lifestyle interventions that required them to reduce food intake by 500 kilocalories per day and to be physically active at least 150 minutes a week.

After 68 weeks, the semaglutide group had lost on average almost 15 percent of their initial weight, whereas in the placebo group it was only 2 point 4 percent. That’s really impressive.

Another drug in this class is tirzepatide that is produced by Eli Lilly under the brand name Mounjaro. It’s also injected once a week. It was approved for the treatment of diabetes both in the USA and in the EU in 2022, but so far it hasn’t been approved for weight-loss.

Several studies have found that in high doses, tirzepatide leads to an even higher weight loss, up to 21 percent. But adverse effects also increased with the dose. About 7 percent of the people on the high dose had to stop treatment because of this.

These drugs have similar side effects: The most common adverse reactions, reported by more than 5 percent of patients, are: nausea, vomiting, diarrhea, abdominal pain, and constipation. These side effects tend to gradually become milder, but for some people the nausea and fatigue become so severe they have to stop taking the drug.

There are other potential long-term concerns that are still under investigation, such as pancreatic cancer, thyroid cancer, damage to the retina, and an increased risk of self-harm. One might also worry that in the long run the body adjusts its receptor response to the abundance of semaglutide, but there’s no evidence for that.

Then there’s the question of what happens if you stop taking the drug. The brief answer is that the weight comes back. The authors of the study that I mentioned previously also looked at what happened when people discontinued the treatment.

After year without medication, those who had received semaglutide had regained two thirds of the weight they’d lost. The ones who had received placebos regained all of it. The blood pressure improvements also faded away when people returned to their old lifestyle.

Then there is the question of what weight you lose on this drug. If you go on a diet, you almost always lose both fat and muscle. Doctors say that a healthy way of dieting should stay within something called the Quarter FFM Rule which means that the Fat Free Mass that you lose on a diet should not be more than a quarter. At least 3 quarters of the weight you lose should be fat.

But the weight that people lost on semaglutide was only 60 percent fat, and that’s despite them also doing exercise. That’s not great, especially not for women who naturally have a higher amount of body fat and less muscle, or older people who have too little muscle mass already.

It might turn out that other drugs are better at that. For example,just a few weeks ago, a group of American researchers presented the results of a phase 2 trial of a drug called retatrutide. They saw up to 24 percent weight loss in the group on the highest dose. And this drug was tested earlier in mice and at least the mice, it seems, lost weight mostly in the form of fat.

Seeing how stunningly successful these drugs are, it isn’t hard to understand why they’ve become popular so quickly, even among people who are not obese. Since the weight comes back once you stop taking the stuff, it’s been used by some as a treatment for special occasions, for example slimming down for a wedding, or for that bikini look on your beach vacation. The majority of those taking it, more than three quarters, are women.

As a consequence, some people with diabetes can’t get Ozempic and some people with obesity can’t get Wegovy because some who don’t have medical need for either but the money for both got their hands on it faster. Some governments have taken measures to protect the people who actually need the stuff. For example, the government of Australia has limited the use of Ozempic to treat type 2 diabetes until the end of December 2023.

Who’s taking it? Well, those who can afford it. According to a 2022 report by the American Institute for Clinical and Economic Review, the monthly cost of a semaglutide treatment in the USA exceeds 1000 US dollars a month.

In the US, some state-level Medicaid programs and private insurances cover the treatment, but the national Medicare program is currently prohibited by law from covering prescriptions for weight loss. The Biden administration however has vowed to do something against obesity, so maybe that law is going to change. If that happens, the costs for obesity treatments in the US will be staggering. 42 percent of American adults are obese, so that could add up to hundreds of billions of dollars per year.

But of course, as we saw in an earlier video, the detrimental health effects of obesity also have enormous economic costs, and those are of the same order of magnitude. And the expenses for the treatment might drop when more drugs are developed that can be produced at a lower price.

Though to be fair, the situation in the US is particularly dire because healthcare there is so expensive. According to data from 2022, a monthly supply of semaglutide in France costs only two hundred and 42 US dollars, in Turkey just 95, and Somalia is one step away from famine.

And then there’s the moral conundrum. The success of these weight loss drugs by suppressing appetite drives home that being overweight is in many cases is a consequence of how our brains are wired. For some people, following their natural feeling of hunger leads to a healthy weight. For others, it leads to being overweight or obese. These people then have the choice of either suffering because they’re hungry or suffering because they’re overweight.

Handing out these drugs on prescription only to those who chose overweight as the lesser evil, and leaving those who permanently starve themselves to their suffering strikes me as morally questionable. I guess this is why those who beat weight gain with dieting and exercise now feel somewhat cheated if others get the same result with less pain and effort, and also why people on Ozempic are often described as lazy.

Another odd thing that’s been happening, especially in the US and the UK is that some people in the body-positivity movement aren’t pleased with the development. The body-positivity movement has been telling obese people to accept their body, which is all well and fine if self-acceptance is realistically the best outcome you can hope for. But semaglutide reveals that, given a choice, many obese people prefer losing weight over accepting it.

In summary, the new weight loss drugs are remarkably efficient, at least as long as you take them. They’re a game-changer for many who are struggling with obesity. But they’re also being used by many others, especially women, who don’t need to lose weight, but have grown up believing that they should. The drugs are currently expensive and hard to get which makes the weight loss game exclusive and creates tension among people who are obsessed with appearances.

But overall, I think it’s a good development because I suspect that as it becomes easier to lose weight for people who don’t need to lose weight, it’ll lose its appeal. Now maybe we could get Novo Nordisk to come up with a drug that helps us reduce nonsense intake?

You can take the quiz here.