Zepbound vs Wegovy Side Effects: What You Need to Know

Every medication comes with trade-offs. The promise of weight loss is powerful. But, if side effects get in the way, they can interfere with progress and make it harder to stay on track.

Zepbound and Wegovy are two of the most widely-used weight loss drugs available today. While they work in similar ways, they have different ingredients. The way your body responds and how you feel from day to day can vary based on the medication you choose.

This guide takes a direct look at Zepbound vs Wegovy side effects, how they compare, and what those differences could mean for your experience.

Comparing Zepbound vs Wegovy Side Effects

When comparing Zepbound vs Wegovy side effects, the biggest differences often show up in how your body reacts during the first few weeks.  Both weight loss medications are part of the GLP-1 receptor agonist family, which means they work by slowing digestion, reducing appetite, and helping regulate blood sugar. But Zepbound also activates a second hormone pathway, GIP, which can amplify both benefits and side effects for some patients.

Let’s take a closer look at how potential side effects compare across key categories.

Gastrointestinal Side Effects

For most people, the most common side effects of Zepbound and Wegovy are gastrointestinal. Nausea, bloating, and diarrhea are all common in the early weeks as your body adjusts to the medication. These side effects are a direct result of how these medications slow digestion and increase feelings of fullness.

In clinical studies:

• Zepbound users reported nausea in about 25% of cases, diarrhea in 19%, and constipation in 17%.
• Wegovy users experienced similar issues, with nausea in 24.3%, constipation in 14.6%, and diarrhea in 7.1%.

Wegovy, which contains semaglutide, typically causes milder gastrointestinal side effects for most patients. On the other hand, Zepbound contains tirzepatide, a compound that targets both GLP-1 and GIP receptors. This dual mechanism can make it more effective for weight loss, but it can also increase the chances of nausea or upset stomach, especially if the dosage is increased too quickly.

That said, not everyone reacts to medication the same way. Some people tolerate Zepbound better than Wegovy, and vice versa. Dosage, eating habits, hydration levels, and underlying health conditions can also play a role in how your body responds.

Appetite and Energy Side Effects

One of the main reasons people turn to GLP-1 medications like Zepbound and Wegovy is their ability to significantly reduce appetite. Both drugs help curb cravings and decrease calorie intake, but these effects can be slightly different with each medication.

With Wegovy, patients often report a gradual reduction in hunger. Meals feel more filling and portion sizes shrink without much effort. In contrast, Zepbound tends to suppress appetite more aggressively, thanks to its additional action on the GIP receptor. This can lead to a stronger sense of fullness, but some patients experience energy dips if they aren’t eating enough.

Low energy or fatigue can has been reported early on in approximately 4% of patients taking these medications, but it’s most common in those who cut calories too quickly. Adjusting meal timing, balancing protein and carbs, and staying hydrated can help smooth out the transition and keep your energy levels move stable.

Cognitive and Mood Side Effects

While gastrointestinal side effects tend to be the most common, some patients may notice shifts in mood, focus, or mental clarity while taking Zepbound or Wegovy.

These cognitive and emotional effects aren’t universal, but when they do appear, they’re usually subtle. Some patients experience mild mental “fog,” become unusually irritable, or feel less motivated. In most cases, these effects are linked to reduced calorie intake or dehydration, rather than the medication itself. If your body isn’t getting the nutrients it needs, your mood and focus can take a hit.

There’s no evidence that either Zepbound or Wegovy causes depression or anxiety, but if you’re prone to mood fluctuations, it’s important to monitor how you’re feeling and discuss any concerns with your healthcare provider. Some patients find that the appetite suppression effects of these medications can lead to overly restrictive eating, which can be concerning, especially for patients who have dealt with eating disorders in the past.

Rare But Serious Side Effects

Most side effects from Zepbound and Wegovy are mild and temporary, but like any medication, there are some risks that deserve closer attention.

Both drugs come with an FDA warning for a possible risk of thyroid C-cell tumors, based on animal studies. While this hasn’t been confirmed in humans, if you have a personal or family history of medullary thyroid carcinoma or MEN 2 (Multiple Endocrine Neoplasia syndrome type 2) your doctor may advise you to avoid GLP-1 medications altogether.

Other rare but serious side effects include:

• Pancreatitis (inflammation of the pancreas)
• Gallbladder issues, like gallstones
• Kidney problems, especially if severe nausea leads to dehydration

These complications are uncommon, but it’s important to be aware of the risks. Severe abdominal pain, yellowing of the skin, or dark urine should be reported to your provider right away.

Why are the Side Effects of Zepbound and Wegovy Different?

Although Zepbound and Wegovy are both part of the GLP-1 medication family, the way they work isn’t identical and those differences can affect how side effects show up for each person. Let’s break it down.

Different Active Ingredients

The biggest difference between the two medications lies in their active compounds.

• Wegovy contains semaglutide, which mimics a single hormone: GLP-1. This slows down digestion, helps regulate blood sugar, and reduces hunger.
• Zepbound contains tirzepatide, which targets both GLP-1 and GIP. GIP (glucose-dependent insulinotropic polypeptide) plays a role in insulin response and appetite regulation, and may amplify the effects of GLP-1 when combined.

Because Zepbound affects two hormone pathways instead of one, it can lead to more noticeable appetite suppression, but also stronger gastrointestinal side effects in some people.

Patient Responses Can Vary

Even with similar mechanisms, each person’s body reacts differently based on metabolism, existing conditions, and sensitivity to hormone changes.

Some patients may tolerate Wegovy easily but struggle with Zepbound. Others might find Zepbound more effective and just as manageable. Factors that influence individual response include:

• Previous experience with GLP-1 medications
• Underlying digestive conditions like IBS or acid reflux
• Dosing schedule and how gradually its increased
• Nutrition, hydration, and overall lifestyle

This is why ongoing monitoring and guidance are so important. At Bariendo, patients receive ongoing care to ensure their treatment plan evolves with them, not just based on weight loss goals, but also on how they feel from day to day.

Wegovy vs Zepbound Side Effects: Which is Easier to Tolerate?

There’s no one-size-fits-all answer when it comes to tolerability. What feels more manageable to one person might be overwhelming to another. That said, trends in clinical trials and patient experiences give us helpful context.

In the SURPASS trials for Zepbound (tirzepatide), participants reported:

• Nausea in 12% to 24% of cases
• Diarrhea in 12% to 22%
• Vomiting in 2% to 13%

In a large study of Wegovy (semaglutide) published in Nature Medicine, 82.2% of participants reported gastrointestinal side effects—compared to 53.9% in the placebo group. The most frequent symptoms were nausea, diarrhea, vomiting, and constipation.

While both medications clearly have digestive symptoms, Zepbound’s dual action mechanism may make it more challenging to tolerate early on.

Ultimately, it’s not just about choosing the right medication. It’s about how it’s introduced and how your care team supports you through the process. At Bariendo, we monitor side effects closely and adjust as needed to make the journey as comfortable and successful as possible.

How to Ease the Side Effects of GLP-1 Medications

Side effects don’t necessarily mean that something is wrong, but they can make it harder to stay consistent. With the right strategies and support, it’s often possible to reduce or prevent symptoms before they become disruptive. Here are a few ways to minimize the early side effects of Zepbound and Wegovy.

Tips for a Smoother Start

Side effects from weight loss medications are the most common during the first few weeks. Eating smaller portions and taking your time during meals can help reduce nausea and stomach upset during this transition period.

When symptoms flare up, choose bland, low fat foods like toast, rice, or broth, which can be easier on the stomach. Avoid fried or greasy foods, which can make side effects worse. Sitting upright after meals and avoiding alcohol can also support digestion.

And while your appetite may be decreasing, staying hydrated is critical, especially if you’re experiencing vomiting or diarrhea.

The Power of Support

Managing the side effects is easier when you’re not doing it alone. Bariendo’s care team provides proactive, ongoing support throughout your weight loss journey. That includes personalized nutrition guidance, check-ins from dietitians and nurse practitioners, and careful medication dosage adjustments based on how you’re feeling. This kind of support ensures that symptoms are addressed quickly and gives patients the confidence to keep working toward their goals.

When to Contact Your Provider

While most side effects are manageable, some symptoms should never be ignored. If you’re experiencing severe nausea or vomiting, signs of dehydration like dizziness or dark urine, persistent or severe abdominal pain, or mood changes that feel out of the ordinary, it’s time to check with your provider. 

These symptoms don’t always mean something serious is happening, but early intervention can prevent them from becoming more disruptive.

Who Are These Medications For?

Zepbound and Wegovy are typically prescribed to adults with a body mass index (BMI) of 30 or higher, or 27 and higher with at least one weight-related condition, such as high blood pressure, type 2 diabetes, or high cholesterol. They’re typically prescribed to people who have tried lifestyle changes like diet and exercise but haven’t seen the results they need.

While there is some risk of side effects, especially early on, the benefits of reaching and maintaining a healthier weight can be life changing. Weight loss has been shown to improve blood sugar control, lower the risk of heart disease, improve sleep apnea, lower blood pressure, decrease joint pain, and support better outcomes for fertility, PCOS, and fatty liver disease.

While these medications can’t replace healthy habits, they can support them by reducing appetite and  improving blood sugar control. Patients taking Zepbound and Wegovy experience an average of 15% weight loss, and even greater success is possible with healthy lifestyle habits.

At  Bariendo, our team carefully evaluates your health history, goals, and lifestyle to determine whether a GLP-1 medication makes sense—or if other options may be more effective for you. 

Make the Right Choice with the Right Care Team

Zepbound and Wegovy are both powerful weight loss medications, but the way they affect your body can feel different. While nausea, fatigue, and digestive changes are common with both, individual responses vary.

It’s also important to know that these medications are typically long-term treatments. To maintain weight loss and metabolic improvements, most patients will need to stay on them long term—similar to managing conditions like high blood pressure or diabetes. That makes tolerability, consistency, and support even more important from the start.

What matters most isn’t just what medication you choose, it’s the support you receive throughout your journey. At Bariendo, we take a patient first approach, helping you navigate side effects with personalized care, regular follow-ups, and expert guidance every step of the way.

If you’re considering Zepbound or Wegovy and want to understand your options more clearly, we’re here to help. Schedule a free consultation to explore your options and take the first step toward a healthier you.