177. Foundayo (Orforglipron): Weight Loss Pill Benefits, Risks & Results

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A new GLP-1 has entered the chat, and I'm already seeing a lot of confusion around it. Meet Foundayo (orforglipron), a needle-free tablet you take once a day with none of the usual restrictions around timing, food, or storage.

On paper, it sounds like the easier option. And for some people, it might be. But like most things in this space, the headline only tells part of the story.

So let me break down what you really need to know before considering it, from cost and access to drug interactions and what the latest trial data shows about maintenance.

Foundayo is not the same as oral Wegovy

This is the mix-up I keep seeing. Oral Wegovy is oral semaglutide, and it's still a peptide. That means it comes with a long list of rules: take it on an empty stomach, wait 30 minutes before eating or drinking anything, and so on. In practice, that's genuinely hard to keep up, even for motivated people.

Foundayo works differently. As a non-peptide small molecule, it's absorbed far more easily, so those rules simply don't apply. You can take it at any time of day, with or without food, and it doesn't need to be refrigerated.

How much weight can you actually lose?

On average, Foundayo leads to about 11–12% total body weight loss. For context:

• Subcutaneous semaglutide (Wegovy, Ozempic): around 14–15%
• Subcutaneous tirzepatide (Zepbound, Mounjaro): around 21%

So yes, it's less potent than the weekly injections. But on its own, 11–12% is a genuinely good amount of weight loss and clinically significant. It can help a lot of people, especially someone who doesn't have as much weight to lose, or someone looking for a maintenance option.

One thing to note: right now Foundayo is approved for weight management, not type 2 diabetes.

Who it might be a great fit for

Foundayo isn't for everyone, but it solves real problems for certain people:

• Anyone who's needle-phobic or anxious about a weekly medication staying in their system for weeks at a time. Foundayo's half-life is roughly 29–49 hours, so it clears much faster than a weekly shot. 
• People who want flexibility as it's much easier to travel with
• Those who need a more affordable maintenance option when the weekly injections aren't covered
• Those looking for a more affordable maintenance option. The weekly injections aren't covered by many insurance plans and get expensive over the long haul. Foundayo offers a route that may be more affordable, and could potentially be covered down the line. That matters a lot when obesity is a chronic condition you're managing for life. 

Drug interactions: what to watch for 

Foundayo is metabolized through the liver, which means drug-drug interactions are a real consideration. Be sure your clinician knows everything you take, including:

• Statins (especially simvastatin)
• Certain antibiotics, antifungals, and HIV medications

This is especially important if you're getting medication through a telehealth service where no one is actually checking in on you. There's also a black box warning for medullary thyroid cancer (seen in rats, not humans, and very rare), plus the usual GLP-1 side effects like nausea and digestive upset (most of which can be managed with the right support).

Can you use it for maintenance?

This is the question everyone wants answered. The ATTAIN-MAINTAIN trial looked at people who lost weight on the injectables and then switched to Foundayo for a year:

• Coming off semaglutide (after losing ~16%): they regained only about 2 pounds and held at roughly 15%.
• Coming off tirzepatide (after losing ~21%): they regained about 11 pounds and held at roughly 17%.

More regain after tirzepatide makes sense, as you're stepping down from a stronger medication to a less potent one.

And don’t forget that a small regain isn't a personal failure. As you lose weight, your hunger signals ramp up and your metabolism adapts, so you're essentially running on a smaller engine. None of that is about willpower. 

My top tip? Work with a clinician who does this all day long, and don't shame yourself. There is always something that can be done for your metabolic health.

If you're weighing whether Foundayo might be right for you, listen to the full episode of The Obesity Guide for the full breakdown. 

TRANSCRIPT:

Disclaimer: The transcript below is provided for your convenience and may contain typos, errors, or grammatical inconsistencies, as it has not been professionally edited or proofread. Please enjoy it as-is and read at your own discretion.

Please note: The content shared in this podcast and blog post is for informational and educational purposes only and is not intended as medical advice. Always consult your healthcare provider for personalized medical guidance.  

Welcome back to another episode of the podcast. How are you all doing? I hope that you are having an amazing summer. For me, the best part of summer is after work, getting for a few hours just to hang out in the backyard. My son kind of runs around and does his thing. He's always got something he's into out there. He is such an outdoor kid. We have these ponds when you down in the neighborhood by us, and it has a little bit of a forest behind it. He's always wanting to go to the pond. It's super fun to just even have an iced water outside, put... We have this blow-up shark thing. I probably talked about it last year 'cause that's when we got it, or maybe it was the year before, I can't remember. But it's a big, think like blow-up bounce house thing, but it sort of stairs and then it has a slide where you come down, and it's like the mouth of a shark, and the water hose is attached to it, so water comes down the-- So when the kids are going through it, they're already getting sprayed, and then water accumulates a little bit like a kiddie pool in the bottom of it. So this is really fun. We always do it for his birthday. We'll do it maybe Saturday, Sunday. It's just so super fun. The only thing that's annoying about it, my husband detests how heavy that thing is because we take it out of our mini barn and oh my gosh, is it a feat to open it up, get it connected properly. But it's one of those things where you invest in it one time, and again, we'll have played with this for years. They even have a patching things that you can buy, God forbid, there's a hole that develops, so you can really take good care of these things and use it over time. So anyway, I have been super loving that.

Today I'm gonna talk about... I have not mentioned on the podcast previously, we've not talked a lot about the new medication, FOundayo, that-- the other name, it's a mouthful. Get ready for it. It's orforglipron. That medication is an oral nonpeptide, meaning it is not a protein It is a small molecule, and it's in pill form, and it can be taken orally daily. This does not need to be refrigerated. It is not dependent on the time of day when you take it. And so today I wanna go through what this is, how it can be taken, what are some things to look out for, what did the trials show us? Let's just go through all of it.

I want to start first with this. People are getting this medication confused with oral Wegovy, which is oral semaglutide. They are totally different. Okay, so let's talk first about oral Wegovy. It was a few episodes back. I'll make sure that we link it in the show notes below this so you can go listen to that episode 'cause it was really great. That is still a peptide molecule. A peptide, meaning the protein, that's what you do when you're doing a sub-Q medication, whether it be Zepbound, Wegovy, things like that. Okay, so the absorption, if you're doing oral Wegovy, that's where they're using that special encapsulation technology that, the SNAC that we talked about, where it's helping so that it doesn't get destroyed in the stomach and the absorption is a little bit more increased. That is making it possible to take an oral peptide. But remember, that is so dependent on you have to take it on an empty stomach, you have to wait 30 minutes before you eat or do anything else. There's all these rules that you have to follow with it. And so the compliance, it's really hard to get someone to follow all that. Now, it was better than nothing if you were someone that didn't wanna do an injection or you were needle-phobic, things like that. Okay, now we're in a different land when we're talking about Foundayo.

So let's just start all the way from the beginning it's a pill. You're gonna take it orally once a day. It does not matter the time of day. This is really nice because some people, it might be easier to take it at night, some people in the morning, this is a small molecule. It is a non-peptide, and so the absorption is much better. It is easier, let me put it that way. The total weight loss that we saw in the trials, it's 11 to 12% of total body weight. This is less than, think, subcutaneous semaglutide, which is Wegovy, Ozempic. That is about 14, 15% total body weight loss. And then when you think about subcutaneous Zepbound, which is also Mounjaro, which is tirzepatide, that is at, let's say, 21% total body weight loss. So you think, "Oh, this is half of it," but on its own, this is actually a good amount of weight loss. This is very clinically significant. This is gonna help a lot of people out if they can get access to this. Let's say that their insurance won't cover Wegovy or Zepbound. If they cover this, they are in a much better spot potentially. So you get a sense of 11 to 12% total body weight loss on average. This might be good for someone where they don't have as much weight to lose to begin with. Sometimes when the body weight set point is lower, I look at options w-where it's totally fine that there's a lower weight loss percentage. Like when we think about generic Contrave, which again has been around a really long time, if I don't have someone that needs to get to 15, 20%, things like that, and maybe they tell me my actual problem are urges and cravings at times that might be an amazing option for them. They might not even need a GLP-1. It's really always important to look at what's going on for people, what are the medical conditions, how far are we trying to get, and this might be a really good option if there's a little bit less weight to lose potentially

. The other area where this is really looked at is for maintenance. We know that the subcutaneous medications are not covered by many insurances. They're very expensive long term. And to have an option where you could maintain with something that's potentially more affordable or maybe even in the future gets covered by insurance, that is much more appealing to a lot of people

and then we also have that camp again, like I talked about above, where you have people where they prefer not to be on something where they have to do an injection. They might be needle phobic. They might have a lot of anxiety about a weekly medication. So I had a, someone join my clinic here recently where they didn't like the thought of doing an injection and then not, and then it being in their system for one, two, three, four, five weeks, they liked the thought of daily doing a medication. Now, the half-life is anywhere from twenty-nine to forty-nine hours, so it's not quite, it's not cleared daily, that means the half-life is by the next time that day when you took that medication, if let's say you're on the faster metabolism side where it's twenty-nine hours, that means you almost have half of it out of your system. So it definitely will take a few days to be fully out, but it is a lot quicker than the weekly medication. Just something to think about there.

The last thing here is cost. So there's just, there's an economic reality when you get on these medications, and I always say that if you do not have a clinician that is thinking about that from the get-go, they are doing you a disservice. For example, some people, they might be getting medication that they know is unaffordable. They know they could maybe do it for six months, but one year, two year, three year, it's not gonna happen. And again, prices and things can always change. It's so sad that in America we have to think about this, but you do need to think about long-term with this, especially if it's a chronic medical condition for you.

Right now, Foundayo is just approved for weight management. It's not approved yet for type 2 diabetes. The one thing that I think really stands out with this medication in a way that clinicians and patients need to be very careful, it's that it's metabolized through the liver. And so when that's the case, you have to worry about drug-drug interactions. For example, simvastatin, this is a cholesterol medication. I call it a dirty statin because it, it interacts and interferes with so many other medications. Back in the day, I hardly had anyone on it. But anyway there are some people that will still be on it, so we'll have to think about dosing for that if you're on it. You might need less. Certain antibiotics, certain antifungals, certain HIV medications. We're gonna have to think really strongly about drug-drug interactions. So this matters because many people are getting help from telehealth services where no one's talking to them, no one's checking in with them, no one knows what's going on with you, and you're just getting random medications. It is vital that if you are on medications that your clinician know. So for this medication, it really matters. I really wanna stress that Okay, black box warning is the same as prior medications here with having a medullary thyroid cancer warning on it. Remember, we see that in rats. We have not, knock on wood, seen that in humans. But again, that's something that if you have medullary thyroid cancer, I will not start a patient on it. When something's a black box warning, we're gonna listen. Now, again, that other forms of thyroid cancer, which are much more common, medullary is hardly anyone, usually fits in a specific syndrome. So again, it's very rare. The other forms, it is fine. It's just with this one that we, have that warning. The things that we always talk about. So pancreatitis, there's a very small risk. Gallbladder disease, with the eyes, retinopathy. Now, hopefully, you already have an ophthalmologist, that they're helping follow along with this. There's the nausea, the vomiting, diarrhea, and again, all the other side effects. You can look at the handout on this. Again, a lot of this, if you are working with a clinician that is familiar with working with these medications and these type of side effects. You know what's occurred to me recently? That obesity medicine physicians, we are actually really good at managing side effects Because I'm thinking back in the day with primary care when people would come in, I don't know that I was this good at dealing with nausea and constipation and diarrhea. I had some basic things in my toolkit, but I feel like being in obesity medicine, I've really had to expand that toolkit so that I have a lot more to offer. You take the medication once a day. You're on it a full month before you go up or seeing about going up, and you don't jump the gun because again, these side effects you need to see are they going to occur or not. But again, most of this can be managed with, when I say lifestyle, meaning what you're eating, how you're moving, how you're hydrating, things like that. For example, if someone has diarrhea, one of my first questions is always, "Is there a high fat content being eaten?" A lot of the time it's after someone has pizza, burger and fries, Mexican food. There are certain things where it might trigger a diarrhea episode for them. And of course, there's many other reasons. If you are having side effects, you should talk to your clinician. This is not we just sit there and we suffer at home.

Okay to summarize up to this point Beyond it being an oral medication that does not need to be refrigerated, that does not need to be taken at certain times of the day, that you have more of that flexibility, where you could maybe travel easier with it. You wouldn't need refrigeration, all those kind of things. That's all amazing.

Let's talk about, though, the million-dollar question, which is what all my patients wanna know about, which is, "Can I use it for maintenance?" So there was a trial here, it was the ATTAIN-MAINTAIN trial. This came at the end of the SURMOUNT-5 trial. So the SURMOUNT-5 trial looked at comparing Wegovy to Zepbound. They looked at how much does someone lose on semaglutide, which in that trial it was sixteen percent, and then they looked at for tirzepatide how much do people lose on tirzepatide? That was twenty-one percent. Okay, so we have those two numbers, very close to what the previous SURMOUNT trials up to that point had shown. So at the end of that SURMOUNT-5 trial, they say, "All right. What happens if someone now for fifty-two weeks is switched to Fondyo?" So they, for one year, are taking this oral medication. If you go to the end of the SURMOUNT-5 trial, the person on average has lost sixteen percent of their body weight. That is thirty-nine pounds on average in the study. When they went on Fontedo for that year, they gained back two pounds on average, so their total body weight loss from the total starting of the medication, even the sub-Q stuff, all the way from the beginning, it'll be fifteen percent. That's pretty amazing if you think about it, that on average this group reached sixteen percent total weight loss with the subcutaneous semaglutide, then they switch over to oral Fondayo, and there they are at fifteen percent total body weight loss, two pounds regain. So gives you perspective, right? So that sounds really amazing as far as I'm concerned for maintenance.

Now, let's talk about with tirzepatide. This is Zepbound. Here's the question, because many people, if you really have a significant struggle with your weight, you will have been transitioned to tirzepatide at some point, assuming that affordability and all of that is in place because it has a higher weight loss, right? So with tirzepatide, at the end of the SURMOUNT-5 trial, they're at twenty-one percent total body weight loss, and on average it's fifty-three pounds that those people lost. Okay. So then they do that year, the fifty-two weeks now on oral Foundayo, and they put back on eleven pounds. But to give context here, they ended at 17% total body weight loss. So it's still higher overall, I mean not that much as far as I'm concerned, but it's still higher overall compared to the group that that did subcutaneous semaglutide and then switched over. But to me, there's a higher regain potential. But to me that makes sense because you're going from a medication tirzepatide that has this 20-plus percent total body weight loss to Fondayo, which is 11 to 12% total body weight loss. And so you're still maintaining a good amount of the weight being off, but it makes intellectual sense to me, and I'm glad that the study backed that up, the fact that they have more regain compared to the other group. It just makes sense, right? Because they've lost more weight, and the medication that they're going on is not as potent, and the study's showing us that. So can it be helpful for maintenance? Absolutely, if you are needing to change. So in my mind, a lot of the reason that people wanna change, it's for affordability reasons. If someone is doing great on a weekly injection, I have not met someone in my clinic yet that is telling me, "Yeah, I wanna switch to an oral medication." Most people at this point, they have well figured out how to travel with it. They like that it's just once a week. The compliance is super high. People are actually doing what they're supposed to do. They don't really wanna change to something when it's working what they're doing. You do wanna change to something when you can't afford what you're doing. And so hallelujah that we have another tool in the toolkit. That is where I'm seeing it, that people want to maintain, and they say this is more affordable, so they go over to that. Again, there can be many other reasons that you make this change. Sometimes with one medication, you're not tolerating it as well, so you try another. Again, there's many reasons, but mainly for maintenance. I love what the study looked at because it gave very concrete answers that on average, again, I'm always like very careful when I'm talking about these very nitty-gritty science things, on average, likely you will have some regain. It will not be super significant, but you will have some. What's interesting is people always beat themselves up when this happens, but you have to keep in mind this is a very complex neurohormonal behavioral... There are so many elements that are involved. When you lost that weight and now we give you a tool that's not as strong for maintenance, you have higher hunger signaling Right? Your ghrelin's like, "Eat, I'm hungry." You might not even notice that's the case though, okay? 'Cause this stuff is subtle, so you might not even notice that. Your metabolism is lower remember, metabolic adaptation's kicking in as you're losing weight. You're thinking you're still doing all the great things, but you have less of an engine, okay? This is not volitional. People are not picking to regain weight. The tool is not as strong, and that's okay hopefully today's episode gave you a little bit of a sense of what this medication is, how it can be used, some things that us as clinicians, we're looking out for, and some considerations if there's a change that's gonna be made. My top tip here is gonna be that you work with a clinician that does this all day long, because if you get switched over to this and things are starting to go south, your clinician can adjust other things with you. There is always something that can be done for your metabolic health, always, always, always. And if you're working with someone that's following you closely, let's say you're seeing them once a month or maybe every three months, whatever it means for your medical team, you will always be able to figure out what to do next. The worst thing that you can do is start to panic and put shame on yourself. If you can step out of that, you are gonna make it so much further long-term with your metabolic health. I just really wanna encourage you with that. All right. I hope that you liked today's episode. This was a little bit more in the weeds. We do a mix on this podcast between a lot in the weeds with medicine and then a lot of practical things and how to do stuff. I hope that you all have a great rest of the week, and we'll talk soon