The short answer: There's no quick fix for obesity

Host Amber Smith: Upstate Medical University in Syracuse, New York, invites you to be The Informed Patient, with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith.

A couple of medications have become popular lately for helping people lose weight. Do they work? Are they safe?

I'll cover that and more with Dr. Timothy Shope. He's the chief of bariatric surgery at Upstate.

Welcome back to "The Informed Patient," Dr. Shope.

Timothy Shope, MD: Well, thanks, Amber. It's great to be back with you.

Host Amber Smith: Ozempic and Wegovy have been in the news lately. And if I understand correctly, both of these drugs contain the same active ingredient. Can you tell us about it?

Timothy Shope, MD: So the medications are in the class called "semaglutides." This is basically the medication form of a naturally occurring GI (gastrointestinal, or digestive) tract hormone called GLP-1. That's glucagon-like peptide-1, a medication that causes a response in the body similar to what that hormone does.

Host Amber Smith: So, semaglutides. I've never heard of that. How was this discovered, or how long have we known about semaglutides?

Timothy Shope, MD: These hormones have been around for a long time. The development of them as a medication, it's kind of a long story. It starts back in the ... actually in the 1980s, with researchers that were working on diabetes, essentially. They were looking at one of the hormones that regulates diabetes, called glucagon, and in that process they discovered GLP-1. And that specific hormone causes a very idealized response in the pancreas, just on the cells that make insulin. They tried giving it to patients, but it didn't work because, basically, it got degraded in the body before it could get to where it would have its effect.

About a decade later, another researcher found a variant of GLP-1 that lasted longer, and, interestingly, he found this actually in the saliva of the Gila monster that lives in our desert Southwest. We knew for a while, I guess, that Gila monsters were able to keep their blood sugar levels pretty stable, even when they had some relative starvation -- hard to find food out there, I guess.

So, they found this hormone in the lizards' saliva, and some modifications, obviously, led to the creation of the first one of these medications, called Byetta. This was used to help control diabetes, but it did need to be injected twice a day. Researchers were trying to figure out ways to make it last longer, so by the 2000s, a medication called liraglutide -- this is really the first of things that led to semaglutide -- was developed, and it really only needed to be injected once a day. It was FDA (Food and Drug Administration) approved for management of diabetes and was marketed as a medication called Victoza.

These medications were found subsequently to have a modest effect on weight loss.

By the time the late 20-teens came around, the medication had been modified to last longer and really only needed to be injected once a week, and this is now what we know as semaglutide.

The first of these was marketed as Ozempic, as you already mentioned. It can't be prescribed, or claimed, to promote weight loss, but I think many of your listeners have seen the advertising or heard the advertising that includes weight loss as a side effect.

So that's really sort of the long story about how these medications came to be, from 30-35 years ago.

Host Amber Smith: So are these prescription medications at this point?

Timothy Shope, MD: They are prescription medications, yes. They can only be obtained by prescription.

Host Amber Smith: And insurances, I guess, are covering them then?

Timothy Shope, MD: Well, so it really depends. Most of the insurance companies will only cover them if the patient is also diabetic; remember that these medications are essentially diabetic medications.

There is one medication that has been approved for use as a weight-loss medication, but even that has to be approved by the insurance company. And there's usually a pre-authorization process that we have to go through for the patient.

Host Amber Smith: So it's not as simple as walking into the pharmacy and grabbing it off the shelf.

You have to have a relationship with a physician to get the prescription, and it seems like it's involved.

Timothy Shope, MD: Yeah, that's correct. I mean, no more involved than any other medication, although again, since it's

newer, there may be some work that needs to be done to have the insurance company approve coverage for it.

But yeah, it's like any other medication that can be prescribed.

Host Amber Smith: Do they actually help people lose weight?

Timothy Shope, MD: They do. Again, not all of them are necessarily designed to do that, so it's essentially sort of a side effect of these medications. The weight loss is modest. It's not great, but it's definitely better than doing nothing, and we don't know how long patients can be on these medications, per se. We don't know everything that might happen to them once they stop taking the medications, although there does appear to be some weight regain afterwards. But yeah, they do actually help folks lose some weight.

Host Amber Smith: Are they safe to take if you don't have diabetes?

Timothy Shope, MD: Well, "safe" is kind of a loaded question. The FDA approved them, so it has to go through some rigorous testing to prove that it's safe for a patient to take. But there's certainly some side effects. There's a lot of GI tract issues that can happen for folks: nausea, vomiting, some abdominal pain. Some folks will get constipation or diarrhea. One of the ways the medications work is by creating a sense of being full. And so there's sort of that constant sense that "I'm not hungry" and "I'm bloated; I'm a little distended" kind of sensation.

Most of the time that goes away a little bit, but that's not anything that's unsafe. It's just maybe not exactly what the patient was looking for. There are some reports of problems with issues with kidneys. And importantly, if you remember that these medications are designed to help patients manage diabetes, it could make someone's blood sugar be very low. And so the patients, especially those that aren't diabetic and have never understood what it's like to take insulin or have a low blood sugar, they need to be coached about that and make sure that they understand what to look out for and what to do if they have the symptoms of hypoglycemia, or low blood sugar.

Host Amber Smith: Do the medications work differently in someone who has a lot of weight to lose versus someone who's got just a few pounds they're trying to shed?

Timothy Shope, MD: I'm not sure what you mean by "work differently."

Host Amber Smith: Well, someone who has 50 pounds to lose, is the medication going to help them lose that as well as it might help someone lose 10 pounds?

Timothy Shope, MD: Yeah, I think so. The data that we understand is that these medications will largely help patients lose somewhere between 10% and 20% of their total weight. So if someone weighs 300 pounds, that would be 50 or 60 pounds. If someone weighs 200 pounds, that would be, you know, 30 or 40 pounds, per se.

So it's really just reflective of whatever starting weight they have and then somewhere between 10% and 20% of that total weight.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith.

I'm talking with Dr. Timothy Shope. He's the chief of bariatric surgery at Upstate, and we're talking about drugs that people may take to help them lose weight.

Let's go over some of the common negative side effects for people who take these medications. You touched on a few of them, but what are the most serious potential side effects?

Timothy Shope, MD: So the serious side effects, again, are those that may lead to some problems with a patient's kidneys and the effect that it has on blood sugar, especially if someone's not prepared to understand what it means to have low blood sugar. When the sugar drops precipitously, a patient could pass out.

And if they're obviously engaged in some physical activity or driving a car or work, that kind of thing, that could be potentially dangerous for them. But there have been some reports of some other types of really serious problems, but it's not clear. Those reports came in patients that were on this medication, or these medications, but it's not clear that the medication caused those problems.

Host Amber Smith: Now, what about the idea that these medications might reduce heart attack or stroke risk? There was something in the news recently about that. Has that been borne out?

Timothy Shope, MD: There's clearly some cardiovascular benefit to losing weight, managing your diabetes, to getting control of your other weight-related medical problems.

So if patients are generally losing weight with these medications, they're going to reduce problems with blood pressure, problems with cholesterol, sleep apnea, all those medical troubles that we know are definitely related to morbid obesity.

Host Amber Smith: Are there things a person can do if they're taking these medications to help minimize the side effects or to help maximize weight loss?

Timothy Shope, MD: The only thing that can really be done to minimize some of the side effects is to essentially slowly ramp up on the dosage of the medication. If you start the medication at a higher dose, it's almost a promise that you're going to have some of these side effects. By starting at lower doses, it allows a body to sort of accommodate to the medication over time. It can be a little frustrating for patients, I suppose, because usually, every month we would then increase that dose, and they may not get the effects of the medication with regard to weight loss that they're looking for until we get to a higher dose.

So there may be some lag in the weight loss associated with the efforts to minimize those side effects. I'm not sure that there's any way that they can maximize their weight loss other than doing the things that we would otherwise suggest: proper healthy diet, exercise, things that we emphasize for every patient that's trying to be serious about weight loss, including our surgical weight loss patients.

Host Amber Smith: What happens when a person stops taking the medications? Are these meant to be lifelong drugs, or can they take them for a while and then stop?

Timothy Shope, MD: So some of it, we don't really know the answer to that. Ozempic, I know has been, not marketed, but sort of suggested, to be something that a patient can be on for life.

I think you have to be pretty smart about stopping these medications, and I don't think a patient should do it on their own. Obviously, this is a medication that's prescribed by a medical provider, and you should definitely have that discussion with that provider. Particularly if you're on it also for management of diabetes, your sugars may be a problem if you stop it.

We do know that there is a weight regain in almost every patient, actually, once the medication is stopped. That weight regain can be at least half, maybe two-thirds, of the weight that was lost within a year of stopping the medication.

Host Amber Smith: Now, you care for patients who are considering surgery after struggling to lose weight.

Do you ever recommend these weight loss medications before surgery or in combination with surgery?

Timothy Shope, MD: We do, actually. We see patients for both surgical and nonsurgical weight loss. Obviously, as surgeons, we have a preference there, but we want to make sure that we have options for our patients.

And our program does incorporate these medications for patients who aren't yet ready for surgery. They're not yet there, emotionally or in their life. They don't want to go through that process. If they ultimately don't achieve the weight loss that they need, many of them will then consider surgery.

But in the meantime, these medications can help with some weight loss. They can modify some of those medical risks that the patients would have. Some surgeons are using these as adjuncts to weight loss, meaning that we can give the medications after an operation. There's actually some data that shows modest weight loss for patients that start these medications years after their weight loss surgery.

You can use these preoperatively for a couple of reasons. Again, that's going to help patients lose weight, which decreases their surgical risk, may help them control their diabetes better, may improve their other medical troubles before surgery. So programs are using them either as a stand-alone option, as a way to prepare, to get ready, for surgery, and then as an adjunct after surgery to facilitate some additional weight loss.

Host Amber Smith: Has the effectiveness of weight loss surgery been compared with the effectiveness of these semaglutides?

Timothy Shope, MD: There's one clinical trial that's out there, so it's not yet, I can't say that it's, definitive, but there's one clinical trial that, a medication called tirzepatide, which has been marketed as Mounjaro, and in the patients that did not have previous weight loss surgery, they had outcomes that were close from the standpoint of weight loss to those that did have surgery instead of being on that medication. This medication's a newer version of these things. It adds another hormone called GIP, or gastric inhibitory peptide, to the GLP-1 hormone, and so the combination appears to be pretty effective. The issue is, there's really not a lot of long-term data on this.

Host Amber Smith: Let me ask, if you would, can you describe who the ideal surgery candidate is for weight-loss surgery? How do you help someone decide whether they're ready for that?

Timothy Shope, MD: Sure. I mean, I think they have to decide that for themselves first.

They have to be in a good place in their lives, where they're committed to this process. They have to be someone who meets the criteria, meaning they have a certain body mass index, or BMI, they have certain medical troubles that they need to address with this.

And they have to have tried something else first, right? We can't just go jump right to surgery. So, the nonsurgical weight loss options that are out there, they should have tried and ultimately not had success with; hopefully, more than one of them. The unfortunate truth of those programs is that the number of patients that have a sustainable weight loss with them is actually very low, so a lot of patients will ultimately opt for surgery, which does have a much better long-term outcome with regard to not just losing weight, but keeping it off.

Those patients that then decide that they'd like to consider surgery, that's when we usually see them, once they've sort of exhausted those nonsurgical means. They've worked with their primary care doctors or their endocrinologist or other doctors, and they say, "Look, I need some extra help here."

When we see them, we have a discussion with them about the process. And that's the reality of this, is that surgical weight loss is a process. It's not an operation anymore, so there's several months of a preoperative process that the patients go through, working with registered dietitians, learning about things that we probably already know, but if you're like me, don't always put into practice. Things like reading product labels, meal planning, these kind of things, when we just kind of grab and go these days.

But if they can incorporate those types of behaviors into their daily lives, and they can commit to them, they can modify, to the best that they can, their other medical troubles, then they're somebody who would be a candidate for surgery.

Host Amber Smith: Well, we talked about the side effects of the medications. Are there side effects of weight loss surgery that people should be aware of?

Timothy Shope, MD: Sure. I mean, any surgical procedure carries some risk. When we talk about risk of surgery, that's really sort of that perioperative period, or the first 30 days or so after surgery.

But I think you're really more talking about sort of the long-term outcomes of surgery, right?

Host Amber Smith: Yes.

Timothy Shope, MD: Yeah, so, over time, patients can have problems with excess skin. There are certainly some behavioral or psychological issues that can arise, meaning we don't do any operations that change relationships with food. We don't do any operations that change your family's relationship with food, so if there's other folks in the house, there may be some issues with regard to meal planning for everybody, making sure that there is not easy access for the patient that's undergoing these procedures to foods that would subvert the process.

So there's a lot of potential psychosocial issues that really are there in the long term.

The medical issues long term: There can be some modest weight regain. It's not usually to the degree that we see from stopping the medications, for example. Usually the medical problems that have been resolved with weight loss surgery, most of them stay resolved unless there's a substantial weight regain.

And I think there's just some hesitancy sometimes on the part of patients to come back to their weight loss surgery program if they have regained the weight. And that's not the right way to think about this. I mean, we're here to help these folks long term, and should they come back to their program, usually there's something we can do to help them turn that around, and at least re-lose much of what they had regained.

Host Amber Smith: So it sounds like no matter which avenue you take, this is not a quick fix.

Timothy Shope, MD: No, it's not, absolutely not. This is not the easy way out. It's not a quick fix. Surgical weight loss is, as I said, a process, and to me, the surgery is really the start of that process. I mean, you have to do a certain number of things to get there, obviously, but really that day of surgery is when things start.

And it's how you use that new tool that you've been given to get those results that you're looking for, and working with your program, working with the dietitians, really just sort of keeping those modified behaviors as part of your daily life for the rest of your life is key to the long-term success.

The medications -- again, there's some potential side effects. We don't know some of the long-term aspects of these things, so it's possible a year or two from now, we'll find that we have to actually stop them after a certain length of time; we don't know.

So it's not an easy or a quick fix, any of it.

Host Amber Smith: Well, Dr. Shope, thank you so much for making time for this interview.

Timothy Shope, MD: Sure. Anytime.

Host Amber Smith: My guest has been Dr. Timothy Shope. He's the chief of bariatric surgery at Upstate.

"The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe.

Find our archive of previous episodes at upstate.edu/informed.

This is your host, Amber Smith, thanking you for listening.