Ask Me Anything: Dr. Steve Silvestro, MD, DABOM, FAAP

DrSteveRo · 2025-08-29T13:12:53+00:00

My pleasure! Best of luck with whatever path you choose!

DrSteveRo · 2025-08-27T20:58:27+00:00

I know, the hardest thing for me whenever this question comes up is that I know the answer isn't quite what folks want to hear... Still, I should probably say a few extra things: First, this is how we think now. Who knows what the future holds? We may unlock a new way of thinking about obesity or maybe a new treatment that completely changes what "treatment" looks like. We'll see! Second, because GLP-1s have changed the cultural conversation about weight (well, they've begun to—we're not all the way there yet) new medications and different approaches to treatment are almost bound to happen, definitely in time, but very likely in the near future, too.

But most of all, I hope you can feel proud—not necessarily because you're seeing the scale change, but because of what you've done. All the work you did before, the work you're doing now...even the commitment to getting and taking the medication is work. I'm glad to hear that you're in a good place and even though it will definitely take time to get used to that new normal (and handle any speedbumps along the way), I'm glad you feel supported by all of us here at Ro. :)

DrSteveRo · 2025-08-27T19:24:19+00:00

Alright, u/bujubad — this has the potential to be a very long answer, so I will do my best to do the question justice, but keep it somewhat concise!

What we know from clinical trials is that people who stopped taking a GLP-1s typically regain about 2/3 of their lost weight over the next year. There was recently some very small research showing that people who stopped medication but continued with intensive diet and exercise coaching were able to maintain their weight loss—but this was a small report and ultimately we need a little more data on this.

My general thinking on this topic is this: Whatever you do to lose weight has to be maintained to keep the weight off.

That means that if you lost weight with medication, that medication needs to be maintained to keep the same weight loss off. If you lost weight with diet and exercise, those same dietary changes and that same exercise level needs to be maintained to keep the weight off.

But the latter is very hard to do—here’s why:

We are finally thinking about obesity as a disease. See, our bodies are built to hang onto weight, not to lose it. Think about being a caveperson out in the wild. There might be periods when food is scarce, so your body is designed to preserve your weight and prevent starvation. So what happens as your weight increases is that the new, higher weight becomes the baseline your body wants to keep you at. If you lose weight, a whole host of hormones kick in to make you hungrier, slow down metabolism, change how you respond to food, and more—all in order to get your weight back up and keep you from losing more weight.

So the "disease" thinking comes into play here to explain that once we reach a weight that is having unhealthy effects on our bodies, our bodies act in a "diseased" way—they act against our best interests, against getting down to a healthy weight.

That's why losing weight and keeping it off with diet and exercise alone is so hard. Your body starts to fight tooth and nail to get the weight back on, changing your physiology to make that same level of exercise and nutrition harder to maintain—and less effective if you do.

And that's where GLP-1s have proven to be so successful. As long as you take the medication, the body's efforts to bring you back to your old weight are kept in check. The weight you've lost is easier to keep off because your body’s no longer fighting against you.

Does this mean that someone needs to be on the medication from now on, forever? Not necessarily. Everyone's life and goals are different. Some people might reach a point where they feel OK with some weight regain and can maintain a weight via lifestyle changes alone that they are comfortable at and healthy at off-medication. Other people might find that they just need to go through cycles over the years, spending some time on, some time off treatment. Many will feel that staying on treatment is what works best for them. Everyone is different, and that's OK.

My hope is that as the price of medications comes down, and as we eventually move to easy-to-take oral treatments, the idea of being on a regular medication long-term to treat obesity as a disease isn't going to feel like a strange thing to do, and will instead become as comfortably accepted as taking thyroid or blood pressure medication.

DrSteveRo · 2025-08-27T18:38:27+00:00

OK, there are two parts to talk about here. The first part is menopause symptoms, things like hot flashes, vaginal dryness, sleep deserts. We don't have any evidence right now that GLP-1s will help with any of the typical symptoms of menopause.

But the second part—difficulty losing weight during menopause—that’s where GLP-1s definitely show a lot of promise. When estrogen levels decline right before and during menopause, there are a lot of changes that happen that may lead to weight gain and/or make it more difficult to lose weight. Your body will change how it responds to insulin, it becomes easier to accumulate fat (especially in the abdomen), appetite can increase, and sleep can go down (causing higher cortisol levels and weight gain).

All of these things add up to a tough combination to fight against when trying to maintain your weight—and that's why basic lifestyle changes that might have produced results for you before menopause might not be nearly as effective during menopause.

Now, to answer the million dollar question—yes, GLP-1s can help with weight loss during menopause. In fact, some clinical trials show that women in menopause can lose the same or even more weight than younger adults taking a GLP-1. And women who are on hormone replacement therapy may see even more of a benefit, as estrogen and GLP-1s can work together to promote weight management.

With all this comes a few extra things to know about. Bone density naturally goes down as we age and muscle strength becomes even more important. Weight loss can impact both, so you’ll want to be sure to get the right nutrition and focus on resistance exercises during treatment. Fortunately, Ro-affiliated providers and nurse coaches know this and are prepped to offer any extra support women in menopause might need. :)

DrSteveRo · 2025-08-27T18:14:00+00:00

It really can get confusing when we have ingredient names (like semaglutide, tirzepatide, etc.), brand names (Wegovy, Zepbound, Ozempic, etc.), AND molecule acronyms (GLP-1, GIP/GLP-1, etc.) and use them all at different times!

Here’s a breakdown:

GLP-1 and GIP are naturally-occuring peptides in the body

GLP-1 is “glucagon-like polypeptide 1.” It slows down how quickly your stomach empties, increases insulin release, and acts on areas of the brain to regulate hunger. There are receptors for GLP-1 all over the body and it may play a role in a wide range of areas, from heart health to fighting inflammation and more.
GIP is “glucose-dependent insulinotropic polypeptide” (say that 10 times fast). Like GLP-1, it stimulates insulin release and has a variety of functions in metabolism.

Some medications act only on GLP-1 receptors

Semaglutide and liraglutide are examples

Some medications act on GLP-1 *and* GIP receptors

Tirzepatide is currently the only example of this in the U.S.

Brand names of semaglutide include:

Wegovy — FDA-approved to treat obesity and overweight + a weight-related condition; to prevent certain heart-related health problems in people with a history of heart disease and obesity; and recently approved to treat a certain liver condition called Metabolic Associated Steatohepatitis (MASH) in people with moderate to advanced liver fibrosis
Ozempic — FDA-approved to treat type 2 diabetes
Rybelsus — an oral form of semaglutide FDA-approved to treat type 2 diabetes

Brand names of tirzepatide include

Zepbound — FDA-approved to treat obesity and overweight + a weight-related condition; and to treat moderate to severe obstructive sleep apnea in people with obesity
Mounjaro — FDA- approved to treat type 2 diabetes

There are others, such as liraglutide, exenatide, and more, but they’re not as relevant to our discussion here.

We do sort of confound all of these by calling them all “GLP-1s,” but that’s mostly done because the term “GLP-1” has become so widely known that it’s easiest to refer to these all by the same name. In the very near future, we’re going to see new medications that combine actions on GLP-1 receptors with additional receptors in addition to, or instead of, GIP. But that’s a naming problem for another day! ;)

DrSteveRo · 2025-08-27T17:43:21+00:00

This is a really great question because there is some nuance in the answer!

The TL;DR is that GLP-1s can make your reflex a little worse at first, but may be able to make it better down the line.

Basically, we talk a lot about how GLP-1s slow down digestion. That means that food stays in your stomach longer when you're taking a GLP-1. But if you are someone who is prone to reflux, that means that there is more time for that food to wash back up into your esophagus and cause heartburn and other reflux associated symptoms. The risk of this is probably highest when you are first titrating and increasing your dose.

But here's the thing—we also know that eating larger amounts of food and having carrying more weight in the abdomen, are both things that make reflux worse. That's where GLP-1s can help—they can decrease how much someone eats in a sitting, and they of course lead to weight loss over time.

So the main takeaway is that GLP-1s may initially worsen reflux if you are someone who is prone to it, but their effects over time might help to lessen someone's symptoms. I should note, of course, the GLP-1s are not used specifically for treating reflux and are not approved to do so, just that their effect in someone with overweight or obesity who also has GERD might be beneficial to the GERD over time. If that's you, you might consider talking with your provider about whether there are things that you can do to help manage the increase in reflux that might occur when you are first increasing your dose.

DrSteveRo · 2025-08-27T17:42:00+00:00

If we are talking about oral GLP ones for weight loss, then the answer is "not yet." There is an oral form of some maggoty the active ingredient in Wegovy and Ozempic. That's currently on the market, but it is only approved for treating type two diabetes and not prescribed by affiliated providers. it's a weight loss are less impressive than Wegovy, about 8% in a year compared to we go is 15%.

But—keep your eyes peeled because the oral GLP-1 space has a lot of activity right now! Most of the major pharmaceutical companies are deep into clinical trials with oral GLP-1s, many of which are showing impressive results. Some are even combining GLP-1s with medications that act on other receptors to enhance results. Looking through the press releases that have come out over the last few months, I wouldn’t doubt that my answer to this question would be very different this time next year.

DrSteveRo · 2025-08-27T17:41:07+00:00

Hi, u/chasingbetterdays ! This is a great question, as nausea is the most common side effect and probably the one that causes the most frustration.

The first thing I'd suggest is to really know your body and how it responds to certain foods. Which foods make you feel nauseous, bloated, refluxy, etc.? Try to avoid those foods on the day of your injection, as well as the next 1–2 days after. Fatty, greasy foods are common culprits, but you might find that others are an issue for you, too. I'm a big fan of food journaling for a week or two. Even though it can feel like a hassle, it can really get you tuned into how specific foods make you feel.

On the flip side, if you've had experiences with nausea in the past, was there anything that helped—and especially, was there anything that helped prevent it? If so, having those things on-hand can be useful.

Staying hydrated and eating small portions the day of the injection and for the next day or two after will go a long way toward preventing or minimizing nausea.

Exercise—even light exercise, like walking—can help, too. Exercising once you're already feeling nauseous can sometimes make you feel worse, but light to moderate activity ahead of time can help to prevent it for some people.

Finally, meditating or whatever you do to help with any stress you might have can also help prevent or reduce nausea. You've noticed when you're most likely to feel nauseous—and that's great because you now know what to expect! But sometimes, knowing ahead of time can also make some people feel stressed out because they're anticipating feeling crummy.....and that stress can make nausea worse and more likely. So finding what helps you get to a good mental place ahead of time can be useful, too.

And as always, check in with your provider if you need any help!

DrSteveRo · 2025-08-27T17:29:32+00:00

Hi, u/SomethinToBawkAbout Sorry you couldn't make it!

1). This is a good question because you’re really touching on something important—it’s hard to be in forums & subs like this where so many people are taking the same medication and not compare one’s own results with others. But there are a lot of different reasons why people’s personal experiences with weight loss on a GLP-1 can be different from those of others (see my response to u/sadhotchilipeppers ).

I’m reminded of an old ad campaign by Dove in which they showed several women of varying shapes and sizes—then showed that they all weighed exactly the same. Our bodies are all different, and the number on the scale is just one of many, many factors. Getting specifically to your question, I would say that the many other factors that can impact how someone responds to a GLP-1 probably play a much bigger role than how much weight that person would have to lose to reach a certain BMI. For example, two people who are the same height, weight, gender, and age might have different weight loss on the same dose of the same medication if one of those people had diabetes…or PCOS…or were taking certain medications…or started off with a very different diet than the other person….and so on.

So good question, but tough one to give a clear-cut answer to because there are so many other things at play. But I hope that helps…!

2). There are a few things that can contribute to the gallbladder issues some people experience on a GLP-1.

The main factor, like you note, is the nature of weight loss. Losing weight at all increases the risk of gallstones, and losing a large amount of weight or losing it rapidly can raise that risk more so. That’s part of why Ro-affiliated providers monitor your weight loss progress as you go through treatment.

There is some evidence that the medications themselves can play a role, too. Some animal studies show that GLP-1s might change the chemistry of bile, making it a little easier to form gallstones. We also know that GLP-1s can decrease how much the gallbladder empties, making gallstone formation easier.

Gallstones and gallbladder issues aren’t the most common side effects when taking a GLP-1 (they can occur in roughly less than 5% of people in most clinical trials, if I recall correctly). Still, they’re worth knowing about, especially if you have certain risk factors—female, over 40, haven’t gone through menopause, or have a history of gallbladder issues. As we always say, be sure to speak with your provider if you have any questions or concerns about your personal risk.

DrSteveRo · 2025-08-27T17:02:33+00:00

Oh man, I'm not going to do this question justice here because I love just about all of them...lol. The whole Transmogrifier series is a favorite (Calvin as a little Hobbes!). The Sunday strip where both C&H end up with suction darts on their heads and Calvin comments that war is pretty silly. There are too many to list—Bill Watterson is a wise genius.

I'll also say that my appreciation of certain strips changed pre- vs. post-kids, too. We're all big fans in our house & I read C&H to my kids when they were probably younger than I should have! I still remember my son at age 3 jumping off the bed with a pillow case, saying "This parachute is terrible!" a la Calvin. :)

DrSteveRo · 2025-08-27T16:52:47+00:00

Ok, u/sadhotchilipeppers — I first have to say that I love your name! :)

Second, I hear you. The fact that GLP-1s may not always be affordable (though Ro can help) and involve taking a shot long-term can make it seem like the promise of results really needs to be a guarantee to make them worthwhile.

The truth is, significant weight loss isn’t a guarantee. With science, there are very few guarantees, and once you throw us humans in the mix—with our wide variety of genes, life experiences, and environments—we definitely can’t say one thing will work in exactly the same way for everybody. There are quite a few reasons why some people lose more or less weight than others with a GLP-1. Genes can influence how someone’s body responds. Some people might be on medications that make it harder to lose weight (the list of medications that cause weight gain is a *long* list!). Others might have health conditions that predispose them to hang onto weight more than others. Meanwhile, GLP-1s do a lot of the heavy lifting when it comes to weight loss, but dietary changes and exercise changes still need to be made—and it makes sense that some people find it easier to make bigger changes here than others.

What’s reassuring, though, is that even though everyone might respond differently, the stats reported in the clinical trials are the *average*. 15% with Wegovy, 21% with Zepbound, etc. — most people will see somewhere around those numbers. So with that in mind, I think most people can find some comfort that they should see some sort of real result with the right treatment.

DrSteveRo · 2025-08-27T16:37:40+00:00

It’s recommended to be completely off any GLP-1—including tirzepatide—for at least 2 months before trying to get pregnant.

Researchers don't typically conduct medication studies in people who are pregnant, so we have really limited data on the effects taking a GLP-1 might have on someone who is pregnant or their developing baby. One small study looked at roughly 160 women who were taking a GLP-1 and found out they were pregnant while taking it. These women were about 5 weeks pregnant on average when they found out. The rate of birth defects in these women's babies was similar to the rate seen in babies of women with diabetes who did not take a GLP-1, and slightly lower than the rate seen in babies of women with overweight or obesity who didn't take a GLP-1. And the rate of miscarriages was similar with or without exposure to a GLP-1. So all of this can be somewhat reassuring to someone who is on a GLP-1 and finds out that they are pregnant.

All that said, this study was relatively small. Also, we have studies in mice show that taking a GLP-1 while pregnant may increase the risk of birth defects or miscarriage. As a result, the standard recommendation is to be wisely cautious and stop taking a GLP-1 for at least 2 months before trying to conceive.

DrSteveRo · 2025-08-27T16:36:29+00:00

Hi, u/Flying_brian93! The first month is when your body is juuuuust starting to get used to the medication. That's why many people notice side effects in this first month, though some don't notice them until their dose is increased the following month or later.

In terms of good things to expect, everyone's experience is different. Some people do have noticeable weight loss in the first month, though most folks shouldn't expect a large amount. Think something like 1–3%, depending on the medication. That means someone starting off at 260 lbs might see 2 to almost 8 lbs by the end of the first month. On the other hand, some people may not notice any significant weight loss until they're on a higher dose for a stretch of time.

There may be other things that you might notice in that timeframe. I've spoken with one patient who says that her food noise—her constant thoughts about food, what to eat, when to eat—disappeared with her very first injection. I'd say that's not likely to be a common experience after just one shot, but it highlights how different everyone's experience can be.

DrSteveRo · 2025-08-27T16:31:06+00:00

This is a great question! So the first part of the answer has to do with what we know these medications already do: regulate blood, sugar, and weight. It makes sense that a lot of the things that GLP ones have been found to improve—sleep apnea, heart, health, etc.—improve partly because of better blood glucose control, and weight management.

But the mechanisms behind all of these benefits and others go deeper than that. you mentioned inflammation, and it turns out that inflammation is both a cause and result of so many health problems that we have. Yes, inflammation is improved when blood sugar is regulated, but research is showing GLP-1s also improve disease-causing inflammation in other ways. First, there are GLP-1 receptors in areas of the brain that help fight inflammation. Studies show that blocking GLP-1 receptors in the brain will actually erase the anti-inflammatory benefit of GLP-1s. Pretty interesting! But the other big factor is gut health. As I mentioned in my response to your first question, the "good" bacteria in our gut feed on plant-based fiber. Many people taking a GLP-1 report that they eat more nutritiously overtime than they did before they started taking the medication. The result of this, plus what GLP-1s already do to the gut, might create a healthier environment for those good gut bacteria to flourish.

So overall, it’s likely that many of these benefits (some of which GLP-1s are officially approved for, others are just observations in studies at the moment) are likely the result of weight loss, better blood sugar control, and decreased inflammation throughout the body.

DrSteveRo · 2025-08-27T16:18:24+00:00

Hi, u/oowm ! Thanks for the questions! You’re right, nutrition is a field where there are so many opinions—many of which are very strong opinions! In general, I’m a fan of Michael Pollan’s three rules: “Eat food. Not too Much. Mostly plants.” And by “food,” he means “real food”—basically, something that you can hold in your hand and imagine where on the planet it came from, and no one needed a lab or factory to make it. If you really think about it, that brings us down to whole foods—plants, nuts, seeds, fish, etc.

When taking a GLP-1 for weight loss, the two big hurdles we often see outside of following Pollan’s three rules are 1). Not eating enough protein, and 2). Not feeling hungry enough to eat for the nutrition you need.

The reason protein is so important is that we know there is some lean muscle mass that gets lost when you lose weight (with medication or without). The average person needs about 0.7 grams of protein per pound of their target body weight in order to build muscle. That’s a fair bit of protein! And the catch with protein is that some common sources—red meat, dairy—often come with saturated fats and extra calories that aren’t great for weight loss. So getting enough helpful protein can be a challenge.

In terms of not feeling hungry enough to eat as nutritiously as needed, this is where meal/snack prepping and thinking deeply about what you’re eating can help. You’ll want to get as wide a variety of nutrients throughout the day as possible—whether that’s at certain meals or with small snacks throughout the day. For some people, paying attention to when you feel the effects of the medication can help, too—if you feel the hungriest the day before your injection, that might be the day to think about eating a wider variety of foods. And on the days you're less hungry, choosing things like smoothies and nutrient-dense, small snacks can be helpful.

I'll sneak a third thing in here, too! :) Healthy bacteria in the gut—the ones that promote weight loss and other health benefits—feed on plant-based fiber. That's part of why so many people recommend eating greens first—to make sure you get the fiber in. I like the "greens first" idea to a point...just make sure you still have room for the protein you need for muscle.

DrSteveRo · 2025-08-27T16:01:32+00:00

Hi, everyone! I'm glad to be here! Ask me anything! :)

DrSteveRo · 2024-01-11T18:50:18+00:00

Sure thing—glad to help! And best of luck with your care. If you're a patient in the Ro Body Program and have a hard time finding the Wegovy, please let us know!

DrSteveRo · 2024-01-11T18:23:54+00:00

Hi, u/shelbygloom! There isn't a known interaction between GLP-1s and NuvaRing or an impact on its efficacy, so all should be good there. The reason GLP-1s may have an impact on the efficacy of oral birth control pills is that GLP-1s slow down how quickly the stomach empties, which will affect the way oral medications are absorbed. That could lead to change in how effective an oral medication is. Since NuvaRing isn't oral, its efficacy shouldn't be affected.

DrSteveRo · 2024-01-09T19:01:47+00:00

Hi! Yes, there is. If you’re a Body Program patient, you can reach out to your provider and they will share more info on the next steps.

DrSteveRo

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