Neha Pathak, MD, FACP, DipABLM: Welcome to the WebMD Health Discovered Podcast. I'm Dr Neha Pathak, WebMD's Chief Physician Editor for Health and Lifestyle Medicine.

For decades, many people have been told that if they ate less, moved more, and had more discipline, their problems with obesity or overweight would disappear. But if you've been paying attention to the science, you know that the concept of “just try harder” has never been the solution. In today's episode, we're talking about why shame and blame have never worked, shared decision-making, and how the new game-changing GLP-1 medications can transform the management of obesity.

We'll explore how these medicines work in the body, who they're actually meant for, what to know about side effects, and how to decide between a weekly shot or daily pill options. More importantly, we'll talk about why any plan for weight management has to start from a place of respect, science, and realistic expectations, not shame.

If you've ever wondered whether these treatments are for people like you, or you're just tired of feeling blamed for your weight, this conversation is for you. First, let me introduce my guest, Dr Robert Kushner. Dr Kushner has had a long, distinguished career as one of the most highly respected weight management experts in the world. He's a former medical director of the Center for Lifestyle Medicine at Northwestern Medicine in Chicago, Professor Emeritus at Northwestern University Feinberg School of Medicine, past president of the Obesity Society, and a founder and first chair of the American Board of Obesity Medicine that certifies physicians in the care of patients with obesity.

Welcome to the WebMD Health Discovered Podcast, Dr Kushner.

Robert Kushner, MD: Thank you for having me. It's a pleasure to be invited to be here with you today.

Neha Pathak: I am very excited to dig into our conversation for today, but before I do, I'd love to ask about your own personal health discovery, an aha moment that you had either in your research or with patients that really informs the work that you do around obesity care.

Robert Kushner: Well, I've had many health discovery moments, but the one I want to mention today, and I did find that out very early in my career, is that everyone has their own story to tell. We often think that individuals living with obesity have one common pathway: they eat too much food and they don't exercise enough, and that can't be further from the truth. So by listening to patients and hearing their life course, I was able to identify each individual's pathway of how they gained weight, including genetics and biology, and then come up with a treatment solution.

Neha Pathak: That's really powerful. So let's start off really with understanding one of the things that is so much being discussed by patients and people in the lay press, and that is GLP-1s as a treatment for obesity. So can you give us a little bit of a background and help us understand what GLP-1s are? What do these medicines do in our bodies?

Robert Kushner: The GLP-1 medications have really transformed obesity care in a way that we had not predicted. Obesity is actually exploding as a topical conversation and in treatment approaches available. In short, what GLP-1 medications are is a family of medications that mimic naturally occurring hormones that are produced in our intestines, often called gut hormones. So when we consume a meal, we start feeling full. Food over time is no longer enticing. We don't want to even finish the meal. After a while, hunger goes down, and that's when the meal is stopped and we eat again at another meal. That all occurs by the release of what's called gut hormones in our intestine, and GLP-1 is one of those naturally occurring gut hormones.

So what these medications do is they mimic these naturally occurring hormones, and we are able to give them back to individuals as medications. So we supercharge or amplify these normal signals that people get, but give them in higher doses for people who are living with obesity. And I think the best comparison I could think of is insulin. We all have insulin in our body, but when individuals have diabetes, we give them higher doses of insulin to control their blood sugar. In the case of obesity, we give higher doses of these GLP-1 medications in order to control appetite so that individuals feel less hungry, more full, reduce “food noise,” and more content between meals. That leads to eating less food over time, and you're able to lose body weight.

Neha Pathak: That's really helpful. So let's take another step back because when it comes to using GLP-1s for the treatment of obesity, I'd love if you could give us a sense of who the patients are that this treatment is indicated for.

Robert Kushner: Well, according to the FDA approval, these types of medications are approved for individuals living with obesity. So that would be someone with a body mass index, or BMI, of 30 or higher. That's generally how we define obesity. Or someone who is in the overweight range, typically a BMI of 27 or higher, with at least one weight-related complication or disease. Examples would be high blood pressure, diabetes, high fats in the blood, arthritis of the knees, sleep apnea, and so forth.

So that's in general who we think are good individuals to consider medication for. And of course, it goes beyond the package insert. It's someone who's already engaged in a healthy diet, but it's not sufficient enough to control body weight. Someone who may have lost weight on one or more occasions in the past but is unable to keep their weight under control, which is very common because of the underlying biology, and is at high risk of having excess body weight. So that's the kind of conversation you have with your healthcare professional. But in general, it's based on BMI and development of other weight-related complications.

Neha Pathak: Very helpful. So along with healthcare professionals, the lay public is also becoming more aware of this long list of GLP-1 drugs that are available on the market, with more on the way it seems every day. So let's focus on the ones that are approved for weight loss. Can you help us understand this newer pill version that's been approved? How does that change your practice and how you think about prescribing these medications for individuals who need it?

Robert Kushner: Well, just to back up one moment, we have two injectable GLP-1 medications that have been around—one since 2021, the other 2023. And those are semaglutide and tirzepatide. These have been the transformative medications. Up until now, the only available route of administration has been a once-weekly injection with a pen that you use yourself at home.

But for the first time now, semaglutide is available in a pill form, and it's the very first time that that is available. So patients now have an option, at least for that medication, to either take it as a once-weekly injection or take it as a daily pill. And this really is, I'd say, a game changer in the obesity realm because a lot of patients may not want to take an injection, but having an option of a pill makes it much more available and agreeable.

Neha Pathak: Help us understand differences beyond just route of administration. Are there differences in how they work? Are there differences in how effective they are? Can you tell us a little bit more about what we know in terms of the differences?

Robert Kushner: Sure. When it comes to outcomes, or efficacy—that is, how much weight loss you can achieve—or the side effect profile, which we'll get into shortly, they're really about the same. Interestingly, the only difference appears to be route of administration. So individuals who take semaglutide by once-weekly injection or by pill are likely to lose about the same amount of body weight.

And that is about one in two, or 50% of individuals in the trials, losing up to 15% of their body weight—that's a lot of weight—and almost a third are able to lose up to 20% of their body weight. And there's very little difference between the two. That is because the tablet has been formulated to deliver a dose similar to what you would be delivering with a once-weekly injection. They really are quite comparable when it comes to outcomes as well as potential side effects.

Neha Pathak: Then let's think practically speaking about the day-to-day when you're taking a pill versus what life looks like when you're taking the weekly shot. Can you give us a sense of what someone needs to know when it comes to things like timing with food and when to take these medications? Can you talk to us first about the injectable and then about the pill?

Robert Kushner: Sure. Let's start with the injection. It is taken once a week in any site on the body, like the thigh, abdomen, or arm, and it's a self-injectable pen. It's not reusable, so you discard it after the injection.

Potential side effects are gastrointestinal side effects—nausea, vomiting, diarrhea, and potentially constipation—and they tend to be most noticeable during the first one to two days after the injection because that's when the dose in the blood is highest. So I tell patients: pick the day of the week when you have the greatest control of your diet over the next one to two days, because controlling your diet can help reduce these gastrointestinal side effects.

As the week goes on, the side effect profile diminishes, although the benefits continue—that is, the effect on appetite.

The semaglutide pill is quite different in terms of how you take it. Although you have the convenience of a daily pill, how you take it makes a significant difference. It must be taken on an empty stomach with generally no more than one to two ounces of water—a sip or two—and you must remain fasting for another 30 minutes.

These rules are very important in order for the tablet to be absorbed. You also have to take it whole; you don't split, crush, chew, or dissolve it. And you should take no other medications during that time. For example, thyroid medication or weekly osteoporosis medications like Fosamax may need similar separation. These are important details we go over with patients, and I provide written instructions so they take it properly.

Neha Pathak: So let's dig a little bit more into what you mentioned around side effects. Are the side effect profiles in general very similar with regard to nausea, constipation, and stomach upset?

Robert Kushner: They actually are. So not only is effectiveness similar, but the side effect profile is also very similar. The most common side effects are nausea, diarrhea, vomiting, constipation, and potentially abdominal pain.

Now, these don't sound very attractive, of course, but we have learned through trials that careful attention to diet can reduce them—such as reducing food intake, avoiding greasy or fatty foods, staying well hydrated, planning meals in advance, and not going long hours without eating.

The other factor is dose escalation. Whether injectable or oral, the dose is slowly increased over time so that for the first month you're on a starting dose, and then each month it is escalated until you reach the target dose. That gradual increase is also very important for reducing side effects.

Neha Pathak: I'm really curious. So when you said for the injectables the side effects predominantly happen or are felt the most in the first day or two and then slowly wane over the week—with the pill, is that something you're going to be concerned about every day?

Kushner: No. It's also going to be during the dose escalation. So if you start with the pill, in which you'd be starting with a, what's called a 1.5 milligram, you're likely to have those side effects when you first initiate the daily medication. But over time, the first days or week or so, they will diminish and will remain lower during the rest of the month. But the following month, in which your prescriber will increase the dose, you're likely to have side effects again. So every time that you increase the dose—and that's important to do, to get to your, achieve the, the target dose—you're likely to have a recurrence of those side effects. Some people, interestingly, have very minimal side effects. Others have side effects that are, are concerning that we have to be very careful managing the person.

Pathak: That's really helpful. So then in terms of your own sort of practice and your patient profile, how are you seeing the pills as a game changer? Is there a patient that now you are able to offer these medications to that before with the injectables, they were less likely to take so? Folks that have injection aversion, are there other types of phenotypes that you're seeing are more open to this new mode of delivery?

Kushner: That's a very good question. In general, I have a what's called shared decision making conversation, and I talk about the pros and cons of both and the patient decides. But if I have to think about a type of patient, someone who has an aversion to an injection, which you just said would be a great opportunity for them to take an oral medication. The other is that the injectable pens need to be refrigerated until they're used. So if someone's doing a lot of frequent traveling or don't wanna put pens and medications through the TSA line, you don't have to do that as well. Other people are really just uncomfortable using an injection pen. They don't have an aversion, but they just are uncomfortable with how to use the administration. That gives them a little bit more opportunity to take a daily medication, which they may be more comfortable doing with some of the other medications they're already taking.

Pathak: So let's dig a little bit more into the shared decision making aspect. When it comes to folks that you might think are not great candidates, whether it's the injection or the pill, is there something in one's medical history or lifestyle that might make you pause or say you're maybe not a great candidate for this medication?

Kushner: Yeah. Well, one thing I think about, which I mentioned already, but I will again, is someone is taking a thyroid medication every day—levothyroxine—that has to be taken on an empty stomach and wait for 30 minutes. If that is someone taking this drug, which also cannot be combined with other medication, you have to wait for 30 minutes, it would probably not be a good addition. Or someone, an osteoporosis medication who also needs to be fasting, although that's taken less frequently. Another one is someone, frankly, who forgets to take medications. They'll say, yeah, I take it maybe four days a week 'cause I keep forgetting to take medications. And again, someone who has a busy schedule, they're out the door right away. They can't think about taking medication, fasting for 30 minutes. They don't have that habit or regularity. I would not be making that recommendation. You really have to be incredibly observant in how you take this medication. Again, no more than one to two ounces of water, which is a few sips of water, and wait 30 full minutes. If you don't follow those restrictions, you will not be absorbing a medication.

Pathak: Really important. So then let's talk about folks that really see these medicines as miracle drugs. So how do you set realistic expectations around how much weight one might look forward to losing? Can you talk to us a little bit about that form of counseling that you give patients?

Kushner: Well, I never used the word magical medication or a miracle drug. I think that's a mistake and I would never say that as a healthcare professional, but they really are incredibly helpful for individuals living with obesity who have been unable to control their caloric intake and diet long term. So they really are—we often say game changer—because they really are that effective. We also talk about that it's not a matter of lifestyle or medication. It's both. Not only is diet change important to reduce the side effect profile, which we talked about already, but following a healthy lifestyle is incredibly important to achieve the health gains that you are looking for: improve quality of life, get your blood sugar down, improve your function, all the other health risks that you may have. So it's very important to do that as well. Regarding long-term, these medications are used as a treatment for a chronic disease. Again, similar to let's say diabetes or hypertension in which we use medications long term. That's how I approach it with my patients. It's not a jumpstarter like a lot of people ask for. And we treat them on individual basis regarding what dose that we are gonna get up to that's gonna be their target dose appropriate for them.

Pathak: What are some other myths or misconceptions that a lot of patients come to you with that you'd like to dispel?

Kushner: The whole idea that it's only a jumpstart, which I mentioned to you already, that is very common and I think that stems from this belief that many, if not most people who are living with obesity have, and that is it's my fault. It's all my responsibility. If I could only get control of my weight, I could take it from there. So the myth is that the medication will get them headed in the right direction, and once they're there, they could take it from there. Like, thanks, doc. I got it. And that's not what obesity is. It's, again, similar to diabetes, is that we're talking about long-term treatment. The other myth or misunderstanding is that there is a strong biologic basis to obesity, and we are treating the biology of obesity with biology, and that is we're using medications that's very important for them to be aware of. And lastly, to reiterate what we already said is that they could take the medication without any attention or thought about how else I live my life, whether healthy, whether I get physical activity—the medication is gonna take care of it for me. And again, that's a myth. You really need to follow a healthy lifestyle of healthy habits along with the medication.

Pathak: I'm also in the lifestyle medicine world, and I would love to dig a little deeper into the lifestyle changes from nutrition, movement, sleep. Talk to us a little bit about how important those are as foundational to taking these medications.

Kushner: Well, I agree with you entirely. Lifestyle is foundational to our health. We talked about diet already, and let me just talk a little bit more about that. The role of diet in these medications is multifold. One is, which we've mentioned, is to reduce the side effect profile of these medications. The gastrointestinal adverse events like nausea, vomiting, heartburn, diarrhea, constipation, and so forth. But a healthy diet is also important for the quality of the diet, to reduce your risk of cardiovascular disease or diabetes or other health problems, to maintain a healthy body composition, specifically muscle mass. When one loses 15 to 20% of your body weight, you are invariably gonna be losing some muscle mass as well. So following a diet that has a high amount of protein—we generally think about anywhere from 60 to 95 grams of protein, or 1.2 to 1.5 grams per kilogram—that's a harder number to keep in mind, but basically a high protein diet—as well as keeping well hydrated, preventing micronutrient deficiencies. Those are vitamins and minerals when one doesn't eat a lot of food. They may end up with deficiency. So some individuals would benefit from a multiple vitamin supplement. So it's important across the board. Then you have physical activity to maintain your wellbeing, your muscle mass, your function, and then we'll throw in sleep and stress management. So you don't wanna get away from this medication is an adjunct or an add-on to everything else that you're doing to take care of yourself.

Pathak: That is critical and I think again speaks to why these medications need to be taken in conjunction with a healthcare professional who can help with all of these other factors as well. I'd love to ask you now a little bit around cost and insurance. Can you talk to us a little bit about how to address the concerns around cost, insurance, and where are the safest places to access these medications?

Kushner: Well, cost, insurance, access, and affordability is what we would call the proverbial elephant in the room. I'll see a patient in my own program and I'll do a full assessment. And in my mind I'm thinking this medication, like one of the GLP-1s, would be really a wonderful addition to their treatment to help them improve their weight and improve their health, only to find out through their insurance or where they get their coverage, it's not available. So that, unfortunately for a clinician, becomes number one decision maker on whether we can use this medication or not. So that goes back to shared decision making. We have a frank conversation with a patient regarding do they have the coverage. I'll always ask them to research that really on their own. Having said all that, costs are coming down in part because of the government renegotiating prices with some of these companies. Increased competition with more drugs going on the market. The oral medication is a little bit cheaper than the injection currently. But if you don't have coverage and you can't afford it, then you're really gonna be using, looking at other cost-effective therapies. And there are other medications that are lower cost. But we continue to advocate for this. We continue to lobby the pharmaceutical industry as well as healthcare insurance industry to help bring those costs.

Pathak: I wanted to go back a little bit to what we were discussing earlier around side effects. Can you talk a little bit about long-term safety? So as you mentioned, this is a medication that people need to really think about as one that is managing a chronic condition. So whether we're talking about pills or shots, what do we know about long-term safety in the range of years?

Kushner: Well, these GLP-1 medications have actually been around since 2005, so that's 20 years, although those medications were developed primarily to treat diabetes. So it's a little different patient population and the doses are different, but we really do have a very long, relatively long experience. If you think about 20 years with these medications, and they've been approved for treatment of obesity since 2014, and then again 2021. And furthermore, these drugs are available worldwide. You're talking about likely millions of individuals over these 20 years that have been exposed to these medications. So that's how we're informed regarding long-term side effects. We haven't seen any serious long-term side effects with this observation. We still, of course, are following patients. We're more familiar with these shorter term side effects like we talked about: gastrointestinal side effects. Some individuals have increased risk of having gallstones or potentially pancreatitis, but we continue to survey individuals long-term and see what the long-term consequences are. But at this point, we are not seeing any unexpected adverse events from long-term use.

Pathak: How should someone be thinking about choosing between these options? What does shared decision making look like with their healthcare provider? What are some of the questions they should be asking? And how can they then make the best choice about the various options that are available to them?

Kushner: I'd like to back it up a little bit and encourage individuals to ask the healthcare provider, I would like to talk about my weight or diabetes. Can you help me to broach that conversation if the healthcare provider doesn't bring it up themselves. And then once you do that, you can ask, am I a candidate for taking a GLP-1 medication? What are your thoughts about a pill versus an injection? So, I would ask the healthcare professional those open-ended questions so that using shared decision making, 'cause that's what the healthcare professional's telling you in that process. And of course, you're telling a healthcare professional what you would prefer, such as, you know, a once a week injection sounds more manageable to me than remembering to take a pill every day.

I don't like an injection. I really would prefer a pill. So I think it starts with having a conversation with your healthcare professional about body weight control and then a full conversation about what do they know and can they help you. And then during that encounter, you should be able to come up with a treatment plan and a prescription for one of these two routes for the medication.

Pathak: So as you know, the FDA recently approved a new oral GLP-1, orforglipron. Given that it's a once-a-day pill without the same fasting requirements, how does that change the way you are thinking about initiating or sequencing treatment for patients with obesity or type two diabetes when you're thinking about GLP-1 options?

Kushner: The availability of orforglipron as an oral tablet increases the options available for patients who would rather take a pill versus taking a weekly injection. So as a clinician, we have more options available to discuss with our patients.

Pathak: Compared to the earlier oral GLP-1 option that required strict timing, are there differences in efficacy or side effect profiles for the new pill that we should be aware of?

Kushner: The average weight loss with orforglipron is about two to 3% less than the other GLP-1 medication, semaglutide. However, the benefits of the medication should not be decided just on average weight loss, but all the other benefits of health that you can get. The side effect profile is actually quite similar. I think the biggest difference, however, is that orforglipron could be taken with or without food at any time of the day, versus oral semaglutide, which must be taken fasting with a small amount of water and not eating for 30 minutes afterwards.

Pathak: Anything else important that you want the audience to know about this new option and how it fits into obesity treatment?

Kushner: The availability of oral medications really extends our opportunity to treat individuals living with obesity or type two diabetes. So patients now can discuss with their healthcare professional what is best for them based on their lifestyle and their daily activities, and what approach to obesity care is going to be most beneficial to them.

Pathak: Well, I want to spend the last few minutes that we have together to you if you have any final thoughts or things that our audience should take away if they're considering having this discussion with their provider.

Kushner: Well, the first thing I want to say is a very important statement, and that is: having obesity is not your fault. It is like other chronic diseases in which there are multiple determinants, including biology and genetics and other social drivers of health, and treatment is available. Healthy living, as we talked about, is foundational, but there are medications that can also assist you in achieving healthy weight and gaining health. We now have, for the first time, an option of using an oral medication in addition to the weekly injectable medications that we've had over the past four or five years.

Pathak: Well, I want to thank you so much for such a comprehensive discussion and for really a lot of clarity. Thank you so much for your time today.

Kushner: Thank you.

Pathak: I'd like to close this episode with my three key takeaways.

First, obesity is a chronic disease, not a personal failure. If you remember nothing else from our discussion today, please remember this. Obesity is not a character flaw or lack of willpower. It's a chronic condition with strong biologic and genetic components. The whole reason medications work is that they target biology-driven appetite signals, not because they suddenly make you more disciplined.

Second, GLP-1 medications are powerful tools, but they're not magic fixes. They work best when they're used long-term under the guidance of a healthcare provider, and combined with healthy lifestyle habits, including healthful nutrition, sleep, stress management, and regular movement.

Finally, shared decision making with your healthcare provider will help you decide whether a shot or a pill is right for you. If GLP-1s are a tool that you should be using in your toolbox, the goal is for your selection to be safe, realistic, and sustainable for you. This requires decisions about your medical history, routines, other medications you're prescribed, your insurance coverage, and your comfort with injections or pills.

To find out more information about Dr Kushner and his work in obesity medicine, make sure to check out our show notes. Thank you so much for listening. Please take a moment to follow, rate and review this podcast on your favorite listening platform. If you'd like to send me an email about topics you are interested in or questions for future guests, please send me a note at WebMD [email protected].

This is Dr Neha Pathak for the WebMD Health Discovered Podcast.