Transcription:
Research: Nutrition and Weight Management with Semaglutide

Melanie Cole (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole, and I invite you to listen as we explore nutrition and weight management with semaglutide. Joining me today is Dr. Robert Kushner. He's a professor of Endocrinology and Medical Education at Northwestern Medicine.

Dr. Kushner, welcome to the show. I'm so glad you could join us today. This is a very interesting topic. So can you start by telling us about your research published in the New England Journal of Medicine for anti-obesity medication?

Dr Robert Kushner: Well, Melanie, first of all, thank you for having me. The study of which I had the honor of being the corresponding author studied the efficacy, safety and tolerability of a drug called semaglutide, actually a drug that's already on the market for treatment of diabetes. It's a self-administered injection that's given weekly used for diabetes and people also can lose weight on this drug when it's taken at a lower dose at one milligram. And that's the approved dose for diabetes.

What this study looked at is the effect of weight loss in individuals with obesity or who were overweight, who did not have diabetes at a much higher dose of 2.4 milligrams. So in this study, which was a global study, about 2000 individuals were randomized for 68 weeks to all of them receiving lifestyle counseling, and then either received the active drug, which was semaglutide 2.4 milligram self-administered weekly or placebo, kind of a top notch prospective study that we do. And the results were really incredibly impressive enough so that it got published in New England Journal of medicine. After 68 weeks, individuals randomized to the active drug lost on average 15% of their body weight versus 2.4% on those who took placebo alone. And just one more thing, Melanie, which really got it called a game changer in the public media, not only is a 15% weight loss not seen before with drugs, but one-third of individuals on the active drug lost 20% or more of their body weight. That's almost starting to bridge the amount of weight loss that some people achieve with bariatric surgery.

Melanie Cole (Host): Wow. That is amazing. So how is semaglutide changing the approach for treating patients and, on average, how long do they need to be on it to reach that full effectiveness?

Dr Robert Kushner: Semaglutide mimics a naturally occurring hormone in our body that's produced from our intestines, fancy name is GLP-1. It's a naturally occurring hormone that causes us to be full, less hungry, more content between meals. So it kind of governs when we eat and when we stop eating, that's a natural physiologic signal. So this hormone which is synthesized as a drug, is then administered back to the body.

Now at lower doses, as I said before, it's used for diabetes. So it helps to increase your naturally occurring insulin, so you can clear your blood of blood sugar and improve diabetes. But at the higher doses, it augments this appetite suppressing effect, which occurs up in the brain. And the way individuals lose weight is that by reducing appetite, so you're less hungry, you're more full, you're more content between meals, you have less cravings for food, less thoughts of food, that's what appetite is. By having that in check, individuals who live with obesity are able to follow a calorie control and a portion reduced diet more consistently and that's what leads to weight loss.

Now, we think of obesity as a chronic relapsing disease. That may be a new concept for a lot of listeners. Obesity is not a self will, brought on to your own control and should be shamed or one does not have enough motivation to lose weight. That's not what it is. We think of it as a biologically based chronic disease. And that's why, by the way, we're even thinking about using medications. But you need to use the drug long-term. And I use the comparison with my patients about diabetes, right? If you had diabetes, you would be on a medication, would improve your diabetes and you have to stay on that medication because if you stop it, the diabetes is likely to come back. Same with hypertension, by the way. So we think of obesity in that same vein, a chronic relapsing disease that if you respond to the medication, it needs to be taken longterm to control the condition.

Melanie Cole (Host): So, what is the FDA saying about it?

Dr Robert Kushner: Well, it's approved this year. It was submitted at the beginning of 2021. It was approved in June of 2021 as the first new medication approved for obesity since 2014. So, we call this a second generation medication, because it's hitting the amount of weight loss we have never seen before, that's number one. Number two, it's leading the way of thinking about obesity as a hormonally-driven condition and thinking about hormonal treatment for obesity, just like we think of hormonal treatment for diabetes where we use insulin.

Melanie Cole (Host): So for other providers, Dr. Kushner, and they're counseling their patients who are going to start to hear about this, can the benefits be sustained? What would you like to tell them about any long-term studies that we're looking forward to? What would you tell them about counseling their patients?

Dr Robert Kushner: Well, I would tell them there's a number of studies that have already been published. They're called step trials for individuals who live with obesity or overweight, and they've looked at a variety of different questions. What happens if you stop the medication? How does it work when you add intensive behavioral therapy? What is the two-year response to the drug? And they've all come out very positive. But the one study you want to highlight is called SELECT. And it's a long-term cardiovascular outcome trial that has already completed enrollment, results should be available in the next few years. And what we're looking at is does the use of this medication actually improve hard cardiovascular endpoints. Those are things like heart attack, stroke, dying of heart disease. And we're interestingly awaiting the results of that trial. And what we're hoping of course is that not only does an individual lose weight and of course improve all of the markers along the way, like blood sugar improves, blood pressure improves, the blood fats improve, inflammatory markers improve. That's already been documented. But this study we hope to show is that it's all going to lead to improvement in cardiovascular endpoints. That will be an exciting outcome and should give a lot of providers and patients confidence that not only is this drug helped me lose weight, it actually improves my quality of life as well as outcomes that we're trying to avoid because of our weight.

Melanie Cole (Host): Certainly true. Those cardiovascular effects will be huge for this. So tell us how you're incorporating these findings into your work at Northwestern Medicine. How will this impact weight management research and potentially other treatment options for patients in the future?

Dr Robert Kushner: Well, Melanie, I run the Center for Lifestyle Medicine at Northwestern Central Region. It's an interdisciplinary group practice of medical providers, registered dieticians, health psychologists, and bariatric surgeons. So we've been using a comprehensive medical model to treat individuals for their obesity for quite a long period of time now. Adding this semaglutide 2.4 milligrams is one more treatment approach of what we've already been using, which includes other medications that are already on the market. How it's going to inform us treatment of obesity is it's leading the way towards hormonal treatment for obesity and there's many other medications and hormonal analogs or agonists. These are drugs that mimic naturally occurring hormones that are already in the works. One has already been submitted to the FDA for approval and others are working their way through the treatment cascade that eventually hopefully will lead to an FDA approval.

Melanie Cole (Host): Can you leave us, Dr. Kushner, with one parting piece of information? This is such an exciting development, and I hope you'll come on and update us as we learn more and as you I see more of your outcomes, but leave us with one parting piece of information for other providers listening and what you'd like them to know about the work and the research that you're doing on semaglutide at Northwestern Medicine.

Dr Robert Kushner: The parting information I want to leave is the challenge that we face in getting primary care providers to embrace treatment of obesity at the primary care level and utilize medications when you're appropriate. The exciting work that I and others are doing to help individuals who live with obesity improve their weight and their medical problems will stay on the floor unless it's picked up and used by primary care providers. This is not a specialty drug. This drug needs to be embraced and used just like drugs we use for diabetes or hypertension.

Melanie Cole (Host): What great information. Such exciting time to be in your field. Thank you so much, Dr. Kushner, for joining us today. And to refer your patient or for more information, please visit our website at nm.org to get connected with one of our providers. That wraps up this episode of Better Edge, a Northwestern Medicine podcast for physicians. For updates on the latest research, medical advancements and breakthroughs. Please follow us on your social channels. I'm Melanie Cole