Exploring gaps in GLP-1 research, care and coverage

Transcript - Exploring gaps in GLP-1 research, care and coverage

Dr. Lydia Alexander: These medications have really changed the landscape. Acknowledging that obesity is a complex, chronic, relapsing and progressive disease and then having medications that can deliver really life-changing weight reduction and weight maintenance has been very important.

Veronica Salib: Hello everyone, and welcome back to Healthcare Strategies. My name is Veronica Salib, and I'm the associate site editor for Pharma Life Sciences. We're here today with Dr. Lydia Alexander, an obesity medicine specialist, and a lifestyle specialist, president of the Obesity Medicine Association and chief medical officer at Enara. Dr. Alexander is also a medical chef based out of the San Francisco Bay area. Dr. Alexander has previously discussed the dangers of compounded GLP-1s with Pharma Life Sciences. Last time we spoke, we had such an informative conversation about GLP-1s and their nuances and I wanted to bring you back so we could dig into GLP-1s a little bit more and discuss the gaps in research, care and coverage. Thank you so much for taking the time to chat with us today.

Dr. Alexander: It's my pleasure.

Salib: Awesome. Before we discuss the gaps in GLP-1s, can you please discuss the progress that we've made in these medications in terms of research, care delivery and coverage?

Dr. Alexander: Absolutely. In the last decade -- a little more than a decade -- we've made tremendous progress. First and foremost, in 2013, the American Medical Association made obesity a disease. That's very important in terms of coverage that it provides to patients with obesity and so that was an essential piece of legislation that passed through the American Medical Association. From a care delivery standpoint, these medications have really changed the landscape because acknowledging that obesity is a complex, chronic, relapsing, and progressive disease and then having medications that can deliver really life-changing weight reduction and weight maintenance of greater than 10%-15%, which reverses many of the complications or comorbidities of obesity, has been very important for the field and for treating patients. From a research standpoint, we knew that these medications provided glycemic control and then additional research showing the benefits from the weight reduction in patients with obesity who did not have type two diabetes has been an important stride in the field.

Salib: Yeah. It's really exciting to see how much we've progressed in our understanding of what obesity is as a disease and in these medications as well. Last time we spoke, you discussed that while these medications are just now gaining a lot of media traction, they have been around for a while. Can you maybe explain why you think they've been gaining a little bit more attention from the public? I'm sure some of us can make our own assumptions, but I'd love to hear from you.

Dr. Alexander: One of the more important ways that these are gaining traction, these medications, beyond obesity being recognized as a disease for over a decade, is the simplified dosing and improved formulations. With the advent of Wegovy -- which is semaglutide -- in 2020 that became FDA-approved for chronic weight management, as well as Zepbound, which is tirzepatide, a little less than a year ago, we have two medications now that are once weekly dosing as opposed to daily injections. That's been a fantastic stride, and then additionally, the weight loss that we see with these new medications is greater than 15 and sometimes greater than 20%, and that's coming right up against gastrectomy results in a nonsurgical environment, making them more accessible, more palatable to patients who need them.

I'd say increased access and broader indications, the SELECT study and many others have shown and are showing there are additional MMO [Morbidity and Mortality in Adults With Obesity] studies coming out that are looking at sleep apnea and many other complications or comorbidities, but the cardiovascular risk reduction of 28% was significant.

A shift in understanding obesity -- again that we see it as a complex, chronic disease and not as a result of lifestyle choices -- has been important. I think public awareness certainly and media influence. There's some good and bad in there for it, but certainly hearing celebrities such as Oprah Winfrey, who we know has struggled publicly for most of her public life, if not all of it, with obesity, talking about these medications and how they had helped her was very important, I think, to recognize the struggles that many Americans face and that these medications help us with metabolic dysregulation on weight and that destigmatization of weight issues and that it's a medical condition, has been really important for these medications to gain traction as well.

Salib: Yeah, I think the destigmatization portion is very key, not just in these medications, but across obesity management. When we talked last time, you mentioned that, and I caught your lecture at a conference in D.C. earlier this year, and you also discussed it there.

Now that we've discussed some of the progress in this class of medications and some of the exciting benefits we've seen, can you share a little bit about the gaps or unknowns in GLP-1s and maybe some ongoing research that's looking to answer some of these questions?

Dr. Alexander: Yeah, absolutely. As mentioned, we've made significant strides, but there's still important work to be done. There are gaps and unknowns to be addressed to maximize the potential to treat obesity and metabolic disease, generally speaking. We don't know really the long-term effects and safety of these medications. They've been around since 2005 for the treatment of type 2 diabetes and, more recently, as mentioned for weight -- for obesity. But beyond 20 years, we don't have a lot of people who have been on these medications for that long. Long-term studies will be important to assess and understand the continued efficacy. Does resistance become an issue? Do antibodies become an issue? Does tolerance become an issue? What happens in the long term in terms of safety and effectiveness will be important and that's related then to the durability of weight loss benefits.

One key is what happens to patients when they stop taking those medications, right? What's the proper way to wean the medications? Who should be weaned from the medications? Is it similar to the treatment of major depressive disorder, where some people may be able to come off the medications after two or three years and will do very well with simple lifestyle measures in terms of behavioral modification, nutrition, physical activity, and other patients may need to be on the medications lifelong because their weight regulatory system has been permanently broken and requires pharmacotherapy to support that individual at a healthy weight? There's limited data on subpopulations and understanding if there are differences in variations in terms of a side effect profile or just the effectiveness of the medications in some subpopulations and also combination therapies.

Zepbound is the first medication, tirzepatide, that is a dual agonist, so it's a GLP-1 and a GIP together in one medication. There are other medications that are in phase trials right now that have additional and different combination therapies within one medication and then also using other anti-obesity medications in conjunction with this class of medications, so we don't have that much understanding and research around combination therapy at this time.

Salib: Yeah, so it's very interesting that these gaps still exist, especially as more and more patients continue to get on these medications or consider getting on these medications and providers have to decide with what information that is currently available.

I'd love to hear about some strategies that scientists, manufacturers or other stakeholders can use to address these gaps or to fill the knowledge gaps.

Dr. Alexander: Conducting, as I mentioned, long-term studies and post-market surveillance is always very important. Once a medication is on the market, it's technically in phase four, and still, there's a lot of data that's collected for those medications. The FAERS, or the Federal Adverse Event Reporting System, is somewhere where clinicians who are using the medications can report adverse events, and so this post-market surveillance is very important because now we're talking about large populations who are taking the medication over time and to understand, are there additional side effects that we're not seeing in phase three trials that we may benefit from knowing here.

Manufacturers, regulatory agencies and scientists can all support the long-term study of these medications and post-market surveillance. Another area, as mentioned, was expanding research into special populations and understanding and developing strategies for sustainable weight loss maintenance, focusing on the longer-lasting formulations or combination therapies or different strategies around therapies.

For instance, some obesity specialists are changing the way that we may dose the medication in a way that is not part of the FDA label, but to extend between injections is one way to do it, and to add adjuvant therapy when there's a new stressor in that person's environment, are some strategies that we have there.

I think always and very importantly, addressing affordability and accessibility challenges is going to be important on the part of the manufacturers, the pharmaceutical companies, policy advocates, insurers, and patient advocacy groups as well. We know that 42% of the U.S. population has a BMI over 30, which means that they have the disease of obesity -- if you use BMI as that measure--and when we include pre-obesity or overweight with a BMI of 27 and greater, which is part of the FDA indication for using these medications, clearly more than half of Americans would fall into that category, so addressing affordability and accessibility challenges I think is going to be really key.

Salib: Definitely. I've heard a lot of discussions about insurance coverage, especially when it is for weight loss and not to manage some other metabolic disorder. People run into a lot of issues when it comes to that, even though so many people qualify for these medications for that reason.

I want to move on a little bit and discuss what the future of these medications is. Do you see continued innovation and if so, in what direction do you see that going?

Dr. Alexander: There is a lot of continued innovation happening at this moment. We are really riding a wave here and I think we're still on the upswing. There are dozens of medications that are currently in phase trials, at least half a dozen or more in phase three trials. Some of the more interesting future-looking pharmacotherapy that is coming to fruition or will be coming to fruition in the next two to three years are additional combination therapies. Triple agonist therapy with retatrutide, is one of them. Amylin and glucagon are other molecules that are being added to these medications and studies are being done to understand what the weight loss outcomes or effects are with these new medications.

I'd say more targeted personalized treatments. So, understanding what leveraging biomarkers predict response to GLP-1s or designing drugs that can be optimized to specific patient subtypes is an example. I will say anecdotally for myself in my clinical practice, I do see patients who will do surprisingly well on liraglutide, which is Saxenda and if I switch them to the once-weekly dosing with Wegovy or Zepbound, they may not have the same results and that's not what the research shows us. It doesn't happen very often, but there are patients who respond better to one therapy versus another. I have a patient who did not do very well on Saxenda or Wegovy and continued to be very hungry -- so, low satiety -- and on Zepbound has done remarkably well. I think that more targeted personalized treatments will be important.

Next-generation, oral, the noninjection options, are also being researched at this moment and in the next 3-5 years will be publicly available. Oral medications that are equally as effective as the injectables. There are medications which may be even transdermal or inhalable options, are a few more to think about and then the expansion of indications beyond weight loss and type two diabetes will be another area and I would say, as always, new market dynamics and policy innovations to be able to create an environment where these medications are more accessible to everyone.

Salib: I want to leave our listeners with a couple things to think on, so I was wondering if you could tell me what are three things that you wish more physicians and providers knew when prescribing these medications?

Dr. Alexander: I likely have more than three things, but briefly, I'll mention that I wish that more patients and physicians knew that comprehensive obesity care is very important. The medications alone in a vacuum are not going to be as effective as we see they are in the research studies, and so having comprehensive obesity care, a multidisciplinary team with an obesity specialist who knows how to treat the disease and to change therapeutic approaches when necessary, is really important and when I say comprehensive care, the focus on nutrition, focus on physical activity, focus on behavioral modification, in addition to the medication. I strongly feel that we shouldn't be just doling out the medication without those supports. People will have more side effects and are more likely to discontinue GLP-1s when they aren't being treated by an obesity specialist and they're not in a practice which offers wraparound care. I think that's really important.

I wish there was more also awareness around what I call part A and part B of treating weight and treating obesity. Part A is the sexy part, and that is the act of weight loss. When you're losing weight, everyone is commenting on it, you are feeling great and it feels very active. Where the rubber really hits the road is, once we reach a weight that feels helpful to us or even our goal weight at this point because these highly effective medications are able to achieve that goal weight for many people taking them, is the long-term active maintenance of the weight lost to achieve all of the benefits that we see in these medications in the trials. I wish more people would know not to discontinue the medication once they've reached their goal weight, but that's really when you want to keep the medication going for a long period of time to make sure to stabilize all the wins there.

I would also say that using people-first language, I wish more physicians or healthcare providers were cognizant of. What I mean by that is using terms like obesity rather than obese. We're talking about the condition, and we're not defining the person as this is the one thing that they are, so obesity. We wouldn't call a person who had cancer cancerous, and so that's the best example that I can give to understand how that may feel to an individual when they're being seen in the office.

To that extent, the new ICD-10 codes, which just became effective Oct. 1, are using people-first language or neutral language, in so far as obesity classes one, two and three, rather than the other ICD codes, which were obesity and morbid obesity due to excess calories. I encourage all clinicians who are treating obesity and coding team to use the new ICD-10 codes that do not have that stigmatizing language.

Salib: Thank you so much for sharing with us and coming on today's podcast and giving us some new insight. It was great to have you. For our listeners, we would love to hear from you. Feel free to reach out with any healthcare-related questions or subjects that you think we should cover by emailing me at [email protected] and if you liked this episode, please consider rating and reviewing us on Apple Podcasts, Spotify or wherever you're listening. Thank you so much for listening.

Kelsey Waddell: Music by Vice President of Editorial Kyle Murphy, and Production by me, Kelsey Waddell. This is a TechTarget production.