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We sit down with David Ahn, an endocrinologist. Join us as we delve into the impact of weight-loss drugs, the role of incretin medications, and their potential to reshape our approach to obesity and overall health.

David Ahn is an endocrinologist and chief of diabetes services, Hoag Memorial Hospital Presbyterian, Newport Beach, CA.

He discusses the KevinMD article, “What we have to gain from weight loss drugs.”

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Transcript

Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast, get CME for this episode by clicking on the CME link in the show notes. Today we welcome David Ahn. He’s an endocrinologist and chief of diabetes services at Hoag Memorial Hospital Presbyterian. His KevinMD article is titled “What we have to gain from weight loss drugs.” David, welcome to the show.

David Ahn: Yeah, it’s great to be on.

Kevin Pho: So let’s start by just briefly sharing your story and journey to where you are today.

David Ahn: Yeah, so interestingly enough, my journey began in diabetes. I am very passionate about diabetes technology. I actually wrote a KevinMD article I think when I was in medical school about how the Apple Store could be a model for health care. So diabetes technology was something that I was very passionate about, and thankfully in kind of the 2010s digital health was really blowing up, at the time that I was kind of going through my medicine residency, my endocrine fellowship, and my early career.

So yeah, I’ve definitely been able to ride the coattails of kind of the growth of health apps, continuous glucose monitoring. And I just kind of like to stay up to date with kind of the newest movements in the field of medicine. More recently that has kind of added obesity medicine to the armamentarium of topics that I cover, because as you know, and as we’ll be talking about, so many of these diabetes medications have been discovered to be very effective for obesity as well, and that’s been a really hot field as well. So it’s been really exciting for the past 15 years being able to just kind of stay on the cutting edge of at least my specialty, and so it was great to write that article.

Kevin Pho: All right, so we’re of course going to be talking about some of these incretin medications like Mounjaro, Ozempic, Wegovy. But before we go into those medicines specifically, just give us your assessment of the current landscape of diabetes medicine today, as we’re talking towards the middle of December.

David Ahn: So for type 2 diabetes, I mean I think endocrinologists across the country would agree that this is really a golden age of medications, primarily driven by the incretins. But even with SGLT2 inhibitors like Jardiance and Farxiga, and then the whole incretin class, it’s great to have options now for our patients that aren’t insulin, of course, for type 2 diabetes. Because as we know, insulin is very effective, but it also often makes it harder to lose weight, and generally patients just have this negative stigma about insulin in general.

So it’s great we have these options in between that can really help improve blood sugar control, help reduce weight, have good cardiovascular benefit, have nephroprotective benefit. And in general, overwhelmingly I think we’ve seen really positive results.

Kevin Pho: Perfect. So let’s start talking about some of these incretin medications. Tell us about your KevinMD article.

David Ahn: Yeah, so the inspiration for that article kind of came around, I was thinking about, at the diabetes center that I’m the director at, we were kind of thinking about what to do and what to talk about in light of November, which is Diabetes Awareness Month.

And I had been seeing a lot of the headlines, I don’t know how wide they go or if it’s just my algorithm and my feeds, but it was kind of talking about how even airline companies are thinking that maybe they’re going to be able to save money on gas if patients lose weight. Walmart I think had published some data about how they saw that people who had filled Ozempic prescriptions were buying less food.

And it kind of made me think, because typically I give a lot of talks on diabetes and obesity, and pretty much the first slide of every one of those talks is like, over the past 40 years diabetes and obesity, it’s a line upward. And when I see these headlines, of course a part of me rolls my eyes as like a skeptical physician, but at the same time it’s kind of like, wow, maybe we finally are going to have kind of an age, like the first decade in the past 50 years, where you start to see that the slope of that change, or maybe even start to level out, or in a perfect world of course start to downtrend.

And so I kind of wrote about why we’re so excited about it. And I think people in general really love learning about incretins. I think there’s a virality around it where people will just click on every article whether it’s good or bad, and I wanted to kind of have a different spin on it, and so that was kind of the angle we decided to go with the article.

Kevin Pho: Perfect. So tell us from a primary care standpoint, and we have so many options to choose when it comes to type 2 diabetes, how should I think about these types of medications?

David Ahn: Yeah, that’s really insightful. I think the guidelines, so if you look at the ADA guidelines and the AACE guidelines, I think they have all been changing slowly, kind of morphing slowly over the past five years. So that, I think historically, five years ago I think it was always metformin first, right, metformin first, then maybe a sulfonylurea, then maybe the fancier medications.

But now, as these medications like the incretins have gotten indications, not all of them of course but some of them have gotten indications for reducing the incidence of repeat heart attacks and strokes, I think we’re seeing them move earlier and earlier in the algorithm. And I think maybe three years ago primary care providers might have been a little bit hesitant to prescribe injection therapy like Ozempic, but now I think given the demand and the weight loss population, I think primary care providers are getting a lot more comfortable prescribing these medications. Which I think is a win for everybody, because we all know that there’s so many patients with diabetes and obesity that it shouldn’t just be limited to endocrinology.

Kevin Pho: So what kind of questions should I ask myself if I wanted to consider an incretin medication for someone in front of me in the exam room with diabetes?

David Ahn: Yeah, so unfortunately, and we can talk about this as much or as little as you’d like, I even tell my patients straight up, I say unfortunately 70 percent of our discussion around these medications actually has nothing to do with medicine. It’s about logistics, it’s about supplies, it’s about insurance coverage. And it’s a good thing, right, because it means so many people are aware of the benefits of these medications. But it is unfortunate that so much of our job as a doctor or health care provider has been around kind of access and helping our patients get a hold of the medications that we prescribe.

So I think that is the biggest burden, honestly in my opinion, is making sure you have the bandwidth in terms of doing prior authorizations, or supporting your patients who may not be able to find a medication in stock and need samples or something like that. So I think that is honestly kind of the biggest challenge in prescribing these medications.

When it comes to medical issues, of course it’s really important to understand that these medications are not one-size-fits-all. It’s not every single person gets on a GLP-1 receptor agonist or something like that. So being very familiar with side effects, being very familiar with kind of the changing guidelines on when to hold a GLP-1 receptor agonist prior to a procedure. And so yeah, I would say you want to approach it just like any other medication, in that there’s a side effect profile that you have to kind of fit and make sure that your patients understand that and fit the right profile.

Kevin Pho: Now for those listening to us that may not be familiar with how these GLP-1 agonists work, give us a 30-second synopsis of how they work.

David Ahn: Yeah, of course. So they work in many different ways, which I think is partially why they’re so effective. So for people with diabetes, and of course it’s not always for people with diabetes, but for people with diabetes, it does help the pancreas increase insulin production, so that’s going to help optimize blood sugar. It also suppresses hepatic gluconeogenesis, so the glucose generation from the liver in the fasting state, so that also helps with blood sugar production.

Probably what it’s most known for is kind of its effects on digestion, so by delaying gastric emptying it helps your body feel more full, and helps you feel less hungry and you stay full longer. And there’s actually a central effect in the brain that helps suppress appetite as well. So kind of that combination of five or six features really add to a benefit in weight loss and blood sugar control when needed.

Kevin Pho: So I know these classes of medication also have various brands within them. There’s oral forms, there’s injectable forms. So from a primary care standpoint, how would I know which one of these medicines is right for my patient?

David Ahn: Yeah, that’s a really good question. So I would say it’s funny, because you would think that if there’s an oral option it would kind of be hands down the best way to go. And so that oral option I’m talking about is called Rybelsus. It’s oral semaglutide, and semaglutide is actually the same thing as Ozempic, so you could argue that it’s an oral Ozempic.

Now it’s a great medication as well, and I do prescribe it frequently, but I will say that for most patients the better option would be an injected option such as Mounjaro or Ozempic. And the reason I say that is because, even though Ozempic is the same medication, the efficacy data is slightly better and the tolerability is slightly better in Ozempic versus Rybelsus. And Rybelsus, even though it’s an oral medication, it does have some kind of nuances to taking it properly. You’re supposed to take it with a few sips of water first thing in the morning, wait 30 minutes before other pills or other food. So in a way a weekly injection is actually kind of easier than doing the juggling act with the Rybelsus.

Now of course we all have those patients that are 100 percent full stop never going to take an injection, and for those patients Rybelsus is a great option, because it does have a weight lowering effect, it does have a glucose lowering effect. But if you’re talking pure efficacy and pure practicality, the weekly injectable options tend to win hands down. But it is nice to have options, because once again not everybody wants to take an injection or is ready to take an injection.

Kevin Pho: Now, patients ask me in the exam room all the time, what’s the expected weight loss when starting one of these medications?

David Ahn: Yeah, that’s one of the million-dollar questions. And I always try to set proper expectations with patients when discussing things. I will cite the clinical trial data, because obviously that’s a decent reference point. Now, I’m going off the top of my head, so I should be close, but in obesity patients, Wegovy was about 15 percent weight loss, and I think Zepbound was closer to 20 percent, I think like 19 percent weight loss.

So I will kind of throw that out there as a metric, but I also am very keen to explain to patients that especially with weight, every person’s journey is very different, right? So even though it might average out to be 15 percent weight loss in Wegovy, if you look at every person’s journey, not every single person started and then lost 15 percent of their weight. Some people might have lost 5 percent of their weight, some people might have lost 25 percent of their weight. So there’s a huge variance on an individual basis. But I do sometimes use the clinical trial data just as a rough starting point, with the big caveat that your mileage may vary.

The other thing that’s important to realize is that the weight loss data is actually different in the diabetes patient population than it is in the non-diabetes patient population. So once again I’m going from my memory, but I believe Ozempic, which is the exact same medication as Wegovy, their weight loss data in the diabetes population is closer to 10 percent, I think just under 10 percent. So you don’t necessarily see the same amount of weight loss in a diabetes patient versus a non-diabetes patient.

Kevin Pho: So you mentioned side effects. What are some of the side effects from this class, both in a short and long term?

David Ahn: Good question. I mean, the most common side effects are going to be GI related, as a result of kind of that slowed gastric emptying. In the studies, overwhelmingly the most common side effect is nausea. In general though, the good news is that the nausea tends to be kind of an initial effect when people are first starting the medication or increasing the dose, and it tends to decrease over time. So as long as I kind of set expectations for patients, that tends to be fairly well managed. The other side effects are going to be things like reflux, some patients will have some constipation, some patients will have some diarrhea, vomiting, but those are less common and they’re all GI related.

Now of course there’s been a lot of hullabaloo about stomach paralysis. I think there were a lot of headlines in the most recent months about that, and I think there were some changes made to the labels for some of the medications. In my practice I have not seen anything that severe, where people have stomach paralysis, but definitely there is some delayed gastric emptying. But overwhelmingly, when I tell my patients, I say, when you stop this medication, any of the effects of it are going to go away, both good and bad.

Kevin Pho: Now, one of the questions I get asked is that, will the weight come back after stopping these medications? Sometimes I’ve talked to other physicians and they say that we need to reframe obesity as more of a chronic disease. So people who take these medicines purely for obesity, tell us what happens if they stop the medications.

David Ahn: Yeah, so that is a really important question that I think responsible physicians and health care providers should make sure their patients have the proper understanding of. I think the general consensus is, like you implied, obesity is a chronic disease, and just like hypertension, just like hyperlipidemia or diabetes, when you start a medication it generally tends to be a chronic medication as well.

And I make it very clear to patients, this is not something where you take Wegovy or Zepbound, lose 30 pounds for your family reunion, and then you can stop the medication and everything is golden. We do know that symptoms like appetite and hunger tend to come back when you stop this medication. There are some clinical trials that have shown what happens when people stop these medications, and once again the statistics are not exactly precise, but people in general regained almost 80 percent of their weight at the end of two years, and I think the curve was still kind of coming back closer to baseline. So overwhelmingly people tend to regain their weight when they stop these medications.

That all being said, I do tell my patients, once again every single person is different, that doesn’t mean every person is going to regain all that weight. And also I tell people, in a way it’s better to start 50 pounds down than to start zero pounds down.

When you talk about it as a chronic medication, I don’t necessarily feel like we have to say you’re going to be on this for the rest of your life. I think there is, just like blood pressure medication or diabetes medication, when I start someone on a diabetes medication my hope is that they make the necessary lifestyle modifications and they lose weight so that we can come off the diabetes medication, or blood pressure medication doesn’t have to be lifelong per se. So I kind of try to set the expectation for somewhere in the middle, like this is not a one-and-done type thing, but at the same time it doesn’t necessarily have to be a lifelong medication, although it is a chronic condition and you will lose the benefit when you stop it.

Kevin Pho: We’re talking to David Ahn. He’s an endocrinologist and chief of diabetes services at Hoag Memorial Hospital Presbyterian. Today’s KevinMD article is titled “What we have to gain from weight loss drugs.” David, give us your crystal ball forecast in the next 6 to 12 months. What do we have to look forward to when it comes to these types of medications?

David Ahn: Yeah, I think going back to the logistics, I’m hopeful that there will be more accessibility for these medications, both in insurance coverage and supply. Right now some of these medications are severely supply constrained due to their popularity, with Zepbound just getting approved. So that kind of will shift some patients over from the Novo products, which are Ozempic and Wegovy, to the Lilly products, which are Mounjaro and Zepbound. I think that will kind of help with the supply issues.

I think also a lot of times, with the popularity of these medications, I’m hoping that come January 1 a lot more insurance plans are going to have coverage for these medications. The battle on employer insurance covering, or Medicare covering, these anti-obesity medications is a big deal. Right now most of these medications are not covered by health insurance, but I think the landscape is slowly changing. So hopefully in the next 6 to 12 months we’ll start to see more and more health insurance plans cover these weight loss medications, and supply will get better, and hopefully there’ll be pressure on these companies to lower their prices.

Kevin Pho: And my final question, David, tell us some of your take-home messages that you would like to leave with the KevinMD audience.

David Ahn: One I guess is kind of a little bit more meta, like stepping back. I would say I think it’s really important as clinicians, especially your newer or younger audience I guess, earlier in their careers, to kind of try to skate where the puck is moving. I think I’ve been really blessed in that regard in my career, whether that’s exploring social media, whether that’s covering new fields of medicine like obesity medicine or these incretin medications. I would encourage people to kind of expand their horizons, or start a podcast. So I think that’s something really exciting, kind of from a little bit of a more meta perspective.

I think when you’re talking about anti-obesity medications, I think they’re only going to get more prevalent, and I think there’s more powerful medications in the pipeline. We didn’t even talk about some of the early clinical trial data from these next generation incretins, which is even crazier. So I think it’s something that if you haven’t kind of familiarized yourself with already, I would heavily encourage you to kind of look into it, to start prescribing it, to start talking to the reps to better understand it, to look into the clinical data. Because I think unfortunately so many people struggle with obesity and/or diabetes, we need really every hand on deck. And so yeah, I would just implore you to fight in the battle for diabetes and obesity.

Kevin Pho: David, thank you so much for sharing your perspective and insight, and thanks for coming on the show.

David Ahn: Of course, my pleasure.