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About two years ago, we released a podcast with Dr. Thomas Wadden of the University of Pennsylvania describing work on a new generation of medications to treat diabetes and obesity. They were really taking the field by storm. Since then, much more is known since many additional studies have been published and so many people have been using the drugs. So many, in fact, the market value of the Danish company, Novo Nordisk, one of the two major companies selling the drugs, has gone up. It is now greater than the entire budget of the country of Denmark. This single company is responsible for about half of Denmark's economic expansion this year. So, a lot of people are now taking the drugs and this is a great time for an update on the drugs. And we're fortunate to have two of the world's leading experts join us: Dr. Wadden, Professor of Psychology and Psychiatry at the University of Pennsylvania School of Medicine and the inaugural Albert J. Stunkard Professor of Psychiatry at Penn. Joining us as well as Dr. Robert Kushner, a physician and professor of medicine at Northwestern University and a pioneer in testing treatments for obesity. Interview Summary Tom, you and I were colleagues at Penn decades ago. And I got frustrated the treatments for obesity didn't work very well. People tended to regain the weight. And I turned my attention to prevention and policy. But you hung in there and I admired you for that patience and persistence. And Bob, the same for you. You worked on this tenacious problem for many years. But for both of you, your patience has been rewarded with what seems to me to be a seismic shift in the way obesity and diabetes can be treated. Tom, I'll begin with you. Is this as big of a deal as it seems to me? Well, I think it is as big of a deal as it seems to you. These medications have had a huge impact on improving the treatment of type 2 diabetes, but particularly the management of obesity. With older medications, patients lost about 7 percent of their starting weight. If you weighed 200 pounds, you'd lose about 15 pounds. That was also true of our best diet and exercise programs. You would lose about 7 percent on those programs with rigorous effort. But with the new medications, patients are now losing about 15 to 20 percent of their starting body weight at approximately one year. And that's a 30-to-40-pound loss for a person who started at 200 pounds. And with these larger weight losses, we get larger improvements in health in terms of complications of obesity. So, to quote a good friend of mine, Bob Kushner, these medications have been a real game changer. Thanks for putting that in perspective. I mean, we're talking about not just little incremental changes in what treatments can produce, which is what we've seen for years. But just orders of magnitude of change, which is really nice to see. So, Bob what are these medications that we're talking about? What are the names of the drugs and how do they work? Well, Kelly, this transformation of obesity really came about by finding the target that is really highly effective for obesity. It's called the gut brain axis. And when it comes to the gut it's starting off with a naturally occurring gut hormone called GLP 1. I think everyone in the country's heard of GLP 1. It's released after we eat, and it helps the pancreas produce insulin, slows the stomach release of food, and reduces appetite. And that's where the obesity story comes in. So pharmaceutical companies have taken this hormone and synthesized it, something similar to GLP 1. It mimics the action of GLP 1. So, you could actually take it and give it back and have it injected so it augments or highlights this hormonal effect. Now, that same process of mimicking a hormone is used for another gut hormone called GIP that also reduces appetite. These two hormones are the backbone of the currently available medication. There's two on the market. One is called Semaglutide. That's a GLP 1 analog. Trade name is Wegovy. Now, it's also marketed for diabetes. Tom talked about how it is used for diabetes and increases insulin. That trade name is Ozempic. That's also familiar with everyone around the country. The other one that combined GLP 1 and GIP, these two gut hormones, so it's a dual agonist, the trade name for obesity is called Zep Bound, and the same compound for diabetes is called Mounjaro. These are terms that are becoming familiar, I think, to everyone in the country. Tom mentioned some about the, how much weight people lose on these drugs, but what sort of medical changes occur? Just to reiterate what Tom said, I'll say it in another way. For Semaglutide one third of individuals are losing 20 percent of their body weight in these trials. For Tirzepatide, it even outpaces that. And I got a third of individuals losing a quarter of their body weight. These are unheard of weight losses. And with these weight losses and these independent effects from weight, what we're seeing in the trials ...