Side Effects on Zepbound and Wegovy- Tips and Tricks
Let’s talk about something no one really wants to talk about—but a lot of people deal with when starting GLP-1 medications like Wegovy or Zepbound: nausea, bathroom issues, and all the gut stuff in between.
If you’ve just started one of these medications, chances are you’ve felt a little queasy, maybe more bloated than usual, or found yourself Googling “Is this normal?” after your injection. You're definitely not alone. These side effects are common, often temporary, and thankfully, manageable with a few practical tweaks.
This guide breaks down why symptoms like nausea, diarrhea, constipation, reflux, and even sulfur burps can happen on GLP-1s—and more importantly, what you can actually do about them. Whether you're just starting out or adjusting your dose, knowing what to expect (and how to manage it) can make a big difference in how you feel day to day.
Let’s get into it.
Why Nausea Happens on GLP-1s—And What You Can Do About It
Nausea is the most common side effect people experience when taking GLP-1 medications like Wegovy (semaglutide) and Zepbound (tirzepatide). It’s a pretty common complaint, but how often it happens—and how intense it feels—can really depend on the medication and the person.
In clinical trials, semaglutide showed higher rates of nausea compared to tirzepatide. Around 44% of people in the semaglutide trials reported nausea, while tirzepatide’s rates ranged from 24% to 31%, depending on the dose. Even the placebo groups had differences—17% of folks in the semaglutide placebo group felt nauseous versus just 9.5% in the tirzepatide placebo group. That might mean the studies were run a little differently, or maybe they were just more tuned in to symptoms.
In real-world practice, many doctors do notice that tirzepatide seems to cause less nausea overall. That said, most people do fine on either medication. Fewer than 5% of participants in the trials actually stopped taking them because of side effects like nausea, bloating, reflux, or constipation. And the good news? These side effects are usually temporary and can often be managed with a few simple tweaks.
So—what can actually help if nausea kicks in?
Practical Tips to Manage Nausea:
Eat Slowly and Mindfully – Eating too quickly or consuming large meals can make nausea worse. Try smaller, more frequent meals, and focus on meals that include protein.
Avoid Common Triggers – Spicy foods, citrus, caffeine, alcohol, dairy, and even certain smells can set off nausea. If something seems to be causing issues, take note and adjust.
Watch Meal Timing – Eating too close to bedtime or lying down right after a meal can trigger reflux or nausea. Give your stomach time to digest.
Limit Fluids During Meals – Drinking too much with meals can expand the stomach and worsen the sensation of nausea. Try sipping water in smaller amounts instead.
Adjust Injection Timing – Because the worst side effects often occur within the first 24–36 hours after an injection, some people prefer dosing on a Friday so they can rest over the weekend.
Try Over-the-Counter or Prescription Relief – Antacids like Tums can be helpful for some. Others may benefit from prescription medications like Zofran (ondansetron), especially if they know they’re prone to nausea or have experienced it in the past.
Explore Gentle Alternatives – Some patients find relief with acupressure wristbands (like Sea-Bands), which are inexpensive and easy to try.
While nausea is pretty common, it usually gets better over time—especially once your body gets used to the medication or your dose levels out. That said, it’s not unusual for nausea to pop up again when you increase your dose, which is why most providers recommend going up slowly.
If you’re someone who tends to feel nauseous more easily, the adjustment period might feel a bit tougher. But the good news is, there are plenty of ways to manage it—and most people are able to stick with the treatment just fine.
Why GLP-1 Medications Can Mess With Your Gut
It’s not the most glamorous topic—but if you’re on Zepbound or Wegovy, we’ve got to talk about poop. Specifically, diarrhea. It’s one of those side effects people are often curious about (and a little nervous to ask about) when starting these medications.
Let’s start with what the numbers say. In clinical trials, around 31% of people taking semaglutide (the active ingredient in Wegovy) reported diarrhea. For tirzepatide (found in Zepbound), the number was a bit lower—about 23%. But here’s where it gets interesting: even the placebo groups had reports of diarrhea. In the semaglutide trials, 15% of people not even on the medication said they had it. In the tirzepatide group, it was 7%. That tells us some of these symptoms might just happen on their own, medication or not—because, let’s be real, nausea and diarrhea aren’t exactly rare in everyday life.
Still, real-world experiences don’t always match the clinical trial stats. In everyday practice, diarrhea isn’t a huge issue for most people on Wegovy. It pops up now and then, but it’s not a top complaint. Zepbound, on the other hand, can sometimes be more of a gut disruptor. While it’s not super common—maybe 1 in 50 to 100 patients—it’s one of the leading reasons people stop the medication. When it does hit, it tends to be more persistent or uncomfortable than expected.
One important thing to keep in mind: just because you had a side effect with one GLP-1 medication doesn’t mean you’ll have the same problem with another. Someone might struggle with diarrhea on Zepbound but feel perfectly fine on Wegovy—or the other way around, especially with constipation. These responses can really vary from person to person.
So, what can you do if diarrhea shows up?
Fiber can help bulk up the stool. A supplement like psyllium or adding fiber-rich foods may make a difference.
Check your diet. Common triggers like caffeine, alcohol, and dairy can irritate the gut, especially when combined with these meds.
Watch out for artificial sweeteners, especially the ones found in protein bars, shakes, or “low sugar” snacks. If you’ve recently started a new eating plan along with a new medication, your gut might be adjusting to both.
Stay hydrated. Diarrhea can lead to fluid loss, so it’s important to drink plenty of water.
Probiotics might help. Whether it’s a more targeted product like Pendulum or a general one from the pharmacy, many people find gut support helpful while on GLP-1s.
And if needed, a short-term dose of an over-the-counter anti-diarrheal like Imodium can provide relief—just make sure to check in with your doctor first.
Of course, if diarrhea becomes a long-term issue or really affects your quality of life, it’s worth talking to your healthcare provider. In some cases, switching medications or adjusting the dose may be the best move.
Bottom line? Diarrhea isn’t fun, but it’s usually manageable—and for most people, it’s not a dealbreaker. These medications can offer a lot of benefits, so the goal is to stay informed, know what to expect, and keep the conversation open with your care team.
Constipation and Upset Stomach on GLP-1 Medications
Constipation tends to show up for a lot of people on GLP-1 medications, especially with Wegovy. On the other hand, Zepbound (tirzepatide) is more often linked to diarrhea, at least based on what’s seen in everyday clinical experience.
In clinical trials, around 23% of people on Wegovy reported constipation, compared to 15% on Zepbound. Interestingly, the placebo group for tirzepatide had more constipation than the placebo group for semaglutide, which suggests Zepbound may actually cause less constipation overall.
That said, constipation on these meds can be frustrating—but it’s usually manageable. Fiber is the first step. Think fruits, veggies, beans, chia seeds, and flax. And if food isn’t enough, fiber supplements like psyllium husk or Metamucil can help. There’s also a fiber blend called SoWell, designed specifically for people on GLP-1s. It was created by Dr. Soa (who shared more about it on the podcast).
Another thing to look at? Your diet changes. A lot of folks add more protein shakes or bars when starting these meds, but the artificial sweeteners in them can backfire and slow things down. Staying hydrated is key—fiber only works when there’s enough water in your system.
Light movement helps, too. Even short walks can get things moving. If dietary changes aren’t cutting it, options like MiraLAX (PEG 3350) can be effective. Probiotics may also offer support.
Some people also deal with reflux or bloating—especially early on. GLP-1 meds delay how quickly food leaves the stomach, which can lead to these symptoms. They usually settle down, but avoiding caffeine, alcohol, and spicy foods can help. And if you’re eating too close to bedtime, it might be worth shifting that earlier.
As always, talk to your doctor if symptoms stick around. There are plenty of ways to make this part of treatment a little easier.
When Belly Pain Is More Than Just Discomfort
When taking GLP-1 medications like Wegovy or Zepbound, s. Knowing the difference can help you decide when it’s okay to monitor things at home and when it’s time to seek medical care.
There are two types of severe abdominal pain to be aware of: gallstones and pancreatitis.
Gallstones can develop during weight loss, regardless of how the weight is lost. It’s not necessarily the medication causing them, but rather the rapid weight loss itself. This risk is a bit higher in young to middle-aged women. If gallstones are the cause, pain is usually on the right side of the abdomen, may radiate to the back, and often appears after eating. It tends to come and go, but if the pain lingers and is paired with symptoms like fever, chills, or weakness, it’s time to call a doctor—or go straight to the ER if you feel very unwell.
The second serious concern is pancreatitis, which is much rarer but potentially more dangerous. This type of pain shows up on the left side and also radiates to the back. It’s typically intense—far more than just discomfort or a cramp—and often comes with nausea, vomiting, and an inability to eat or drink. Most people experiencing this kind of pain end up in the emergency room due to how severe it feels. If you’ve had pancreatitis in the past, you may be at higher risk, and your doctor might avoid prescribing GLP-1s depending on your history.
Outside of those more serious cases, milder abdominal discomfort is also possible. In clinical trials, about 10% of Wegovy users and 5% of those on tirzepatide reported moderate belly pain. This type of pain tends to come and go and may be triggered by certain foods. While it's usually nothing to worry about, it’s always worth bringing up with your doctor so they can assess whether further evaluation is needed.
Another side effect that some patients report is gas and burping, including a particularly unpleasant type known as sulfur burps. These are thought to be linked to how food moves (or lingers) in the gut, possibly due to changes in the microbiome. They’re more common in people taking tirzepatide than semaglutide, and while not dangerous, they can be pretty uncomfortable.
In many cases, this symptom improves over time. Some common triggers identified in clinical practice include dairy and red meat, but it varies from person to person. Experimenting with your diet can help pinpoint the cause. In the meantime, simple remedies like Tums, Gas-X, or acid-reducing medications may provide relief. Probiotics, gum, or mints can also be helpful in managing symptoms.
In summary, while abdominal discomfort is a known side effect of these medications, most cases are mild and manageable. Still, it’s important to stay alert to more serious signs like persistent pain, fever, or severe nausea, and to talk to your doctor if anything feels off.
Red Patches, Itchiness, and More: A Look at Common Reactions
Aside from gastrointestinal side effects, injection site reactions are another common concern with these medications. The reactions are typically mild and not the same as a severe allergic response. Most often, they appear as red, itchy patches around the injection site—about the size of a quarter. However, in some cases, the area affected can be larger.
Around 5% of people using either medication experience this side effect. While these reactions don’t usually worsen over time, they can still be bothersome, especially if you’re injecting weekly. To help manage the irritation, it’s often recommended to apply a topical steroid, like cortisone, to the site. In some cases, taking an antihistamine like Benadryl can also help relieve the itching.
Do Medications Like Zepbound Worsen Mental Health?
Another side effect that has gained attention—especially in the media—is the potential for mood changes, including symptoms of depression or even suicidal thoughts. This is an area that continues to be closely monitored and discussed, as mental health concerns are always important to take seriously when starting any new medication.
However, the real-world data tells a more nuanced story. While it's easy to worry about the potential for psychiatric side effects, these concerns appear to be more theoretical than practical when we look closely at the evidence.
In clinical trials, 9.5% of people on semaglutide experienced a worsening of psychiatric symptoms. Interestingly, a higher percentage—12.7%—experienced the same thing in the placebo group. This suggests two things. First, some individuals may struggle with worsening mental health regardless of whether they're on medication or not. Second, there’s a possibility that semaglutide might actually have a stabilizing or even slightly protective effect, though it’s unclear whether this difference was statistically significant.
As for Zepbound, the rate of mood worsening was extremely low at just 0.3%. While the studies aren't directly comparable due to differences in design, this still provides some reassurance.
When mood changes do happen in patients, it's important to look at the bigger picture. Is another medication being affected, perhaps in terms of how it’s absorbed? Is the person going through major life stressors? Could weight loss itself be unearthing past trauma or creating new social dynamics that are emotionally challenging? These are all possible factors that may influence mental health during treatment—but they don’t necessarily point to the medication as the root cause.
In short, while monitoring is important, the available data doesn’t suggest that these medications are directly contributing to a decline in mood for most people. Instead, it's often a combination of life circumstances, personal history, and physiological changes that deserves a closer look.
Is Losing Too Much Weight a Concern?
Excess weight loss is a concern that often comes up, especially when people reach a healthy weight after struggling with excess weight for so long. The idea of losing too much weight can be worrisome, particularly when individuals drop to a weight they've never been at before. This is a common issue for many who reach a normal BMI, as they might question whether they’re truly at a healthy weight. However, it’s important to understand that reaching a healthy weight for your body is not necessarily a problem. For instance, if you weigh 150 pounds and you’re at a healthy BMI, that’s perfectly fine, even if it’s a weight you’ve never been before.
It’s also not uncommon for friends or family to voice concern, especially when they see someone lose a significant amount of weight. While their worries may come from a place of care, it’s essential to stop making others feel self-conscious about their weight loss. The key is to check in with a doctor or health professional if there are genuine concerns. It’s important for people to focus on healthy habits and get advice from experts rather than relying on opinions that might not be based on health facts.
In many cases, once people achieve a healthy weight, there’s little need for concern unless their BMI drops below 18.5, which is considered underweight. That level is extremely lean and typically associated with athletes like marathon runners. It’s rare to see such low BMIs from weight loss medications, and when it does happen, it’s often seen after surgery, not through medication. As long as muscle mass is maintained, and blood work shows no issues, there's no need to panic about losing too much weight.
When it comes to weight loss, the focus should be on maintaining lean mass, particularly muscle, rather than simply the number on the scale. Healthy muscle mass helps maintain strength, energy, and overall health. If someone’s BMI is in the 20-21 range and they’re eating well, staying active, and their health markers are good, there’s no need to worry. It’s all about finding a balance and making sure that the weight loss is in line with healthy habits that keep the body strong and well-nourished.
GLP-1 medications like Wegovy and Zepbound can be incredibly helpful tools for managing weight and improving metabolic health—but they’re not always smooth sailing. Nausea, constipation, diarrhea, reflux, and even the occasional sulfur burp can make the first few weeks (or dose increases) a bit of a challenge.
The good news? Most of these side effects are temporary, manageable, and often improve as your body adjusts. With a few smart tweaks—like changing how and when you eat, watching for food triggers, staying hydrated, and using supportive tools like fiber or probiotics—you can often ease the discomfort and stay on track with treatment.
As always, check in with your healthcare provider if anything feels off, especially if symptoms linger or get worse. Personalized guidance can make a big difference.
You’re not alone in this, and you don’t have to figure it all out by yourself.
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