Obesity Expert Highlights 2021 Research Success, Looks to 2022 and Beyond

Donna Ryan, MD, points to the 2021 approval of semaglutide 2.4 mg for the treatment of obesity, the anticipation of a 2022 FDA submission for the combined GLP-1/GIP agonist tirzepatide, and to a cardiovascular outcome trial now underway with semaglutide in adults with obesity and without diabetes as the most important news items in treatment for adults with overweight and obesity. Together they reflect the past, present, and future of the study of weight management.

"By far, the big event in 2021 was the approval by the FDA of semaglutide 2.4 mg given by injection weekly for obesity treatment," said Ryan during an interview with Patient Care Online (PCO). PCO invited Ryan, professor emerita at Pennington Biomedical Research Center in Baton Rouge and immediate past president of the World Obesity Federation, to highlight the progress made last year in treatment for overweight and obesity and to offer a look ahead to the promising research in 2022.

Donna H Ryan, MD, is professor emerita at the Pennington Biomedical Research Center in Baton Rouge, LA, and immediate past president of the World Obesity Federation. She directed clinical research for 22 years at Pennington Biomedical and her own research encompasses key roles in the DASH (Dietary Approaches to Stop Hypertension), POUNDS Lost, DPP (Diabetes Prevention Program) and Look AHEAD studies. Ryan's continuing research interests focus on translation of effective weight management into primary care practices.

The following transcript has been edited lightly for style.

Patient Care Online. I'm Grace Halsey, senior editor of Patient Care Online. In January we touch base with thought leaders and principal investigators in key therapeutic areas, to learn from them where they thought the greatest strides were made in their area of medicine in the past year, and to talk a little bit about where they see things going in the future. I'm speaking today with Dr. Donna Ryan about advances in therapeutics for obesity and weight management. Dr. Ryan is Professor Emerita at Pennington Biomedical in Baton Rouge, Louisiana, and immediate past president of the World obesity Federation.

PCO. 2021 wasn't completely the year that we had hoped it would be after coming through COVID-19 in 2020. But despite that, there were quite a few remarkable clinical trials published in the area of obesity and weight management and significant advances made in therapeutics. Could you highlight what you feel were the most important evolutions during 2021?

Donna Ryan, MD. By far, the big event in 2021, was the approval by the FDA and marketing of semaglutide as Wegovy. Semaglutide is a GLP-1 receptor analog, and it's already on the market for diabetes. But it was approved by the FDA at a dose of 2.4 milligrams given by injection weekly, for obesity treatment. This drug is generating enormous interest. The reason being it produces a lot of weight loss. It goes to the brain, and it helps with appetite. So, it reduces hunger. And it helps you eat smaller meals, and you're less susceptible to these highly rewarding foods that we're all tempted by. The average weight loss with Wegovy is about 15% from baseline. This is about twice as much as our older antiobesity medications. And it's enough weight loss to really get some good health benefits.

We know that if we can get 15% weight loss, we can really get some improvements in symptoms of obstructive sleep apnea. If you have diabetes and haven't had it for a very long time, just a few years, 15% weight loss gives you a pretty good chance of going into remission of your diabetes. We also know that this 15% weight loss will clear the liver of about 60% of fat and we’re seeing growing problems in obesity with fatty liver disease. It's the amount of weight loss that really produces a lot of health benefits. And everybody's very excited about it.

Now there's one snag, I have to tell you about. And that is, you know, the year 2021 was the year of supply chain issues. And we've had problems with supply chain for Wegovy. It's actually part of the pen that's used to inject the drug has had issues. And so, there's been a slowdown in getting the drug out to market.

You know, our insurers, particularly the private insurance and the large private insurers have been reimbursing at higher rates than ever, for medications for obesity. And so, we were really beginning to see a lot of uptake of Wegovy, but the supply chain has sort of put the damper on getting that drug really into the population. So, we're expecting by the middle of 2022 to see that change.

PCO. Do you think that semaglutide 2.4 was the most important addition to the treatment options that are now available?

Ryan. It’s really a game changer because of the amount of weight loss.

The other thing that's coming with that drug is a cardiovascular outcome trial. That's a large study—this one has more than 17 000 people enrolled who have established cardiovascular disease and overweight and obesity, but they don't have type two diabetes. This is the first cardiovascular outcome trial in people who don't have type two diabetes, but who have had a stroke or heart attack or peripheral arterial disease. These are people at very high risk for subsequent stroke or heart attack or sudden death from cardiovascular causes. And you know, semaglutide has been shown to reduce these events in people with diabetes, if it, as we hope, demonstrates this in people without diabetes, but with obesity, it will really change the game. And what it means is that people who are at high risk for cardiovascular disease need to be taking this drug to prevent subsequent events. So that's, that's coming, it probably will take about two years for the results of that study to come in. But it's, it's a something to look for on the horizon.

Semaglutide is also the first of what is going to be a whole series of new medications for weight management. The next one up, which would probably come out next year, is going to be terzepatide. And that's a drug that's being developed for diabetes and for obesity. And the interesting thing about this medication—it’s a GLP-1 receptor agonist, but it also hits a new receptor, the GIP receptor, and we think it's going to produce a little more weight loss than we're seeing with semaglutide. So, the news is good there. Let's hope let's fingers crossed, that this medication makes it through the FDA with good safety, because the efficacy is going to be there.

And we need we need these medications for our patients with obesity and with diabetes, right?

PCO. It's so interesting how the cardiovascular outcome trials which were required of new diabetes medications have become, they've just shifted the whole study of treatment for diabetes, and now obesity and cardiovascular disease.

Ryan. The FDA did require cardiovascular outcomes trials with our older medications, but they were not designed to show superiority of the medication, just to prove that it wasn't any worse, what’s called a noninferiority trial. And so those are the kind of studies that the FDA required for Contrave, Qsymia, and, well, lorcaserin, Belviq, when that drug was still on the market, but this, this is different. This is superiority.

So, this will be our first study in for an antiobesity medication that hopefully will demonstrate superiority in reducing cardiovascular events.