Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
People may not understand the potential limitations of the new class of Ozempic-like anti-obesity medications, especially given the wide hype these drugs are receiving. For example, the drugs don’t work for everybody, and even when they do, weight loss stalls out after a year. The drug insert included in every package of the high-dose Ozempic used for weight loss shows these graphs. Here’s weight loss on high-dose semaglutide, also known as Ozempic, and sold as Wegovy, versus placebo. As you can see, after about a year, weight loss stops, even if you keep injecting yourself with the drug. Is it because you’ve plateaued at a normal weight? Sadly, no. They started out obese, and they ended up obese. Why does the weight loss stall out?
Because of what’s presumed to be a near-exponential rise in calorie intake, as the same amount of effort to cut calories—whether through willpower, drugs, or surgery—is met with increasing resistance, as ongoing weight loss activates your feedback-control circuit, stimulating your appetite. So, at first, the massive GLP-1 activity triggered by the drugs lowers your appetite, but as you lose weight, your body fights back, ratcheting your appetite back up. So, the same amount of massive GLP-1 stimulation causes less of an appetite suppression. Within 12 months, this resistance, together with the decreased total energy expenditure from being lighter, matches the persistent effort to cut calories, and with calories-in matching calories-out, weight loss plateaus. Here it is, graphically. The same thing happens whether you’re restricting calories on a diet, injecting these fancy new GLP-1 Ozempic-type drugs, or going under the knife for bariatric surgery.
Take high-dose Ozempic. After the three-month ramp up in dose, people are eating nearly a thousand fewer calories every day. No wonder they’re losing weight. But then, the body fights back, pushing against the high GLP-1 signaling and jacking their appetite back up. Not all the way up, because they’re still injecting these drugs every week; so, they still appear to be eating 400 fewer calories a day than they used to. So, if they’re eating less, why aren’t they continuing to lose weight? Because they’re expending 400 fewer calories simply because they aren’t dragging 30 extra pounds (13 kg) around with them wherever you go.
What happens if you stop the drug? In this study, everyone was started on high-dose Ozempic for five months and started to lose weight. Then, some were randomized to be unknowingly switched to placebo injections. Those who continued taking the drug continued to lose weight, until the plateau. Whereas, those who switched to placebo started to regain all the weight they had lost.
It’s the same with tirzepatide, sold as Zepbound. As soon as people stop taking the drug, the weight starts coming back, and any benefits that had been achieved start to evaporate. Check it out: here you can see what happens when people stop taking the drug after being on it for more than a year. The pounds pile back on, two-thirds regained within a year, and here are some of the evaporating benefits. Blood pressure came down with the weight loss, but then climbed right back up as if they never even took the drug in the first place. And inflammation and blood sugars started creeping back up too. So, not only does weight loss stop as soon as you go off the drug, but the weight you had lost before comes back.
So, like in this study, you may have started out obese, and ended up obese, and to maintain your less-but-still-obese status, you have to keep taking these drugs––presumably every day or week for the rest of your life. So, these are forever drugs, the golden goose for big pharma, drugs for lifestyle diseases that you may have to take lifelong, since you aren’t treating the underlying cause—a fattening diet.
As the popularity of Ozempic-type drugs, like semaglutide, soars, what do we need to know about their effect on our weight? Even these new-fangled anti-obesity medications aren’t a magic bullet. The overall weight-loss benefits are notable, but nonetheless limited. The best of them can produce a 20 to 25 percent weight loss, but they still leave most users overweight or obese, only modestly less so––and, thus, still facing major health risks. And, of course, the drugs are only effective as long as they’re used. Not only does the weight loss plateau, but years or, presumably, a lifetime of continuing treatment is required just to maintain their initial benefits. And most people stop taking them within months before they even reach an effective dose.
The manufacturers recommend ramping up usage over four or five months. But based on 169,000 real-world patients using GLP-1 drugs for weight management, most individuals didn’t stay on their prescribed treatment for even three months, which suggests it was unlikely they were achieving clinically meaningful weight loss. In fact, only about half take the drug for even two months, and 80 percent quit by six months. Why don’t people stick with it?
One reason may be that these drugs are costly. And costly is a bit of an understatement. The costs of these drugs are enormous, like $1,000 a month in perpetuity, since any lost pounds can pile back on if you stop taking them. Wegovy, the high-dose Ozempic used for weight loss, costs up to about $1,350 dollars a month. So, that’s like paying $15,000 out-of-pocket every year. And some say healthy eating is expensive? You could have Food Is Medicine programs deliver healthy food to your door—for ten times less. You could even have fully-prepared meals delivered to your door at a fraction of the cost of the drug.
Of course, the drugs should get cheaper. There are hopes that competition will lower prices, but each GLP-1 drug is protected by approximately 20 patents, many up to 2040 or beyond; so, they probably won’t get much cheaper any time soon.
But isn’t obesity itself expensive? Even factoring in health benefits and discounted prices, these drugs may not be cost-effective. In one analysis, total annual health care costs doubled for patients, going from about $13,000 per person before starting the drug to $26,000 after. Now, the benefits of weight loss accrue over time, but because lost pounds are commonly regained after stopping the drug, an additional vexing conundrum is created for payers like insurance companies. Why shell out all that money to get people to take the drug, if most are just going to stop taking it and simply regain the weight?
Why are the drugs so expensive? “There is no rational reason, other than greed,” according to Senator Bernie Sanders, noting that Canadians and Germans are paying about 10 times less for the same drugs. Wegovy, the high-dose Ozempic used for weight loss, can sell for $1,300 a month in the U.S., but less than $100 a month in the U.K. Here’s what different countries pay for the exact same doze of Ozempic. The researchers even calculated the “estimated minimum price”––how much it could be manufactured and sold profitably for. So, for $40 a month, Novo Nordisk, the makers of Ozempic, could be pulling in a 10 percent profit margin. But why make 10 percent profit when you can make more than 3,000 percent profit?
But don’t they need those huge profit margins to recoup research and development? I mean it’s expensive to develop drugs. Novo Nordisk spends twice as much money enriching its shareholders, by doing things like stock buybacks to jack up stock prices, than it does on all R&D. In fact, most big drug companies spend more on these kinds of self-enrichments than actual research. Whatever the actual cost of developing a drug, drug companies may spend far more on marketing drugs than developing them.
While gouging patients $1,000 a month for their drugs, Novo Nordisk was spending millions of dollars wining and dining doctors to prescribe more of them. Hundreds of thousands of meals and snacks served to promote drugs like Ozempic. In fact, Novo Nordisk was actually suspended from a pharmaceutical industry trade association for failing to disclose its sponsorship of a training course for healthcare professionals that just so happened to plug one of its GLP-1 drugs––a violation bad enough for the Royal College of Physicians to sever its ties with the drug giant.
Anyway, back to our original question: why do so few people stay on these drugs? Well, people may start out obese and end up obese. Is it worth paying $1,000 a month just to stay less obese? You can see why people might just cut their losses. But no, the study showed that most people who quit these drugs after just a few months were not only insured, but they had their drugs covered by their insurance. So, maybe the reason most people quit so soon after starting is not due to their cost, but rather their side effects, which we’ll cover, next.
Please consider volunteering to help out on the site.
