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The Weight-Loss Drug Revolution, Part 1: Why These Drugs Work So Well

Beverly Tchang, an endocrinologist at Weill Cornell, joins the show to explain the impacts of this new generation of weight-loss drugs

Ozempic Manufacturer Sued Over Side Effects Of Medication Used For Weight Loss Photo by Jaap Arriens/NurPhoto via Getty Images


Today’s podcast is about the weight-loss drug revolution—which I believe might be one of the most important stories in the world right now. Despite all the attention weight-loss drugs are receiving, it’s possible that they might soon affect the world even more than we realize as they teach us about the science of human metabolism, decision-making, and even free will. Beverly Tchang, an endocrinologist at Weill Cornell, explains how these drugs work, what they mean for people with diabetes and obesity, and how to wrap our minds around their stranger and spookier side effects.

If you have questions, observations, or ideas for future episodes, email us at PlainEnglish@Spotify.com.


In the following excerpt, Beverly Tchang gives Derek an overview of the weight-loss drugs that were available before drugs like Ozempic came along and how these new medications are impacting patients.

Derek Thompson: And before we talk in-depth about the impact of this weight-loss drug revolution, I’d love to have a clearer sense of who your patients were and what their options were before anyone had ever heard the word “Ozempic.” What kind of patients did you see, and what was their menu of options when they came to see you?

Beverly Tchang: So the patients I was seeing before the “Ozempic revolution” have really been people who had both obesity [and] diabetes. They had more complex medical issues, including high blood pressure, heart disease, etc. And the difference nowadays though is that there’s a greater public awareness, I think, of obesity as a disease and all of its consequences. So now we’re seeing patients come in earlier, so to speak, in this disease process before they develop diabetes, even before they develop prediabetes. And that’s the shift we’re seeing.

Thompson: And how would you describe the level of enthusiasm for this new generation of weight-loss drugs among your patients compared with the options they had before? Have you seen anything like this in your history as a clinician?

Tchang: Oh my gosh. It’s overwhelming, really. I mean, it’s exciting on one end because I think everyone is finally taking it seriously, and they’re looking at it as a true medical problem. It’s not just a lifestyle choice. It’s not something where if you diet hard enough or exercise hard enough, you’ll be able to fix it. We realize now from decades of scientific research that there’s a real biology behind obesity. And you can diet and exercise all you want, but if your genetics and your hormones are not in balance, then you’re going to be fighting that the whole way. And I think that’s the experience of so many of my patients.

Thompson: Do you remember the moment when you first heard of Ozempic—semaglutide—or read the results of some of those early reports? I mean, I know that in talking to other people on this show, including Susan Yanovski at the NIH, who we spoke to last year, her perspective was that she had for years said, “If only there was some way to get bariatric surgery without the surgery, to have some way to provide a medication that could, for the vast majority of patients, almost guarantee 15 to 20 percent weight loss but without a surgery intervention. I mean, that would just be a miracle drug,” she was saying.

And then when she heard and when other obesity researchers—I think she described this conference they were at—first saw the results of semaglutide or a similar GLP-1 agonist, I mean, people were standing up and clapping like they were watching the end of Cats, West Side Story, some Broadway show. So I wonder, did you have a similar moment of just [standing] up in your seat, “Oh my God” when you began to realize what was coming down the pike?

Tchang: I’m not as exciting as that, Derek, I’ll be honest. But I’ll tell you this: Because we’ve been in this space for so long, we’re in the weeds. We see a transition over decades. Before Ozempic, we were treating people with obesity with two or three medications. They had to take multiple pills a day just to get 5 percent weight loss, 10 or 20 pounds of weight loss. For someone who’s 200 pounds, that’s not a lot, but it’s better than nothing. And then as we developed more and more anti-obesity medications around the 2010s, 2014, we are accessing more weight loss. So more than 5 percent. We’re looking at 10 percent with some of the combination medications, for example. And so we’re incrementally increasing that weight loss over decades, really.

And then enters something like semaglutide. When we hit that 15 percent weight-loss threshold, suddenly we’re seeing the reversal of those other medical problems that we talked about: the diabetes, the high blood pressure, the high cholesterol. Whereas before, when we’re losing 10 pounds, 20 pounds, we’re seeing improvements. Maybe their blood pressure is getting better. Maybe they’re taking one blood pressure medication instead of two now because we got them to lose 20 pounds. But as Dr. Yanovski has alluded to, once you’re getting into these thresholds of bariatric-surgery-level weight losses, we’re seeing reversal of diabetes, hypertension, high cholesterol, etc.

Thompson: And how would you explain to a layperson what makes semaglutide and other GLP-1 agonists special? Why do they work so well, do you think?

Tchang: It’s a little bit of a chicken or the egg question because I think we’re learning about the medication just as much as the medication is working for us in the sense that because the medication works so well, it tells us, “Oh, I think now we’re really getting at the root cause of obesity.” Before, I don’t know if you remember orlistat, but it was this medication branded under the name Xenical but available over the counter as Alli. And it worked by reducing our body’s ability to absorb fat from our diet. It didn’t work that well. It was approved back in 1999. It didn’t work that well.

Now that we’re looking at medications that address the peptides, the proteins produced in our gut that then travel into the brain, into the areas of the brain that control appetite, those are working super well. I think we’re realizing, “Oh, that’s really the mechanism of obesity or at least one of the mechanisms of obesity.” So I think that’s why these GLP-1s are working so well because we are learning more about the biology and what causes obesity. And then there’s also just the convenience of it too. A lot of these medications are available as once-a-week injections, and I think a lot of patients really, really like that.

This excerpt was edited for clarity. Listen to the rest of the episode here and follow the Plain English feed on Spotify.

Host: Derek Thompson
Guest: Beverly Tchang
Producer: Devon Manze

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