Zepbound side effects: what to know before taking it

There’s a newer medication on the weight loss scene: tirzepatide. Tirzepatide is sold by Eli Lilly and Company under the brand-name Zepbound (zehp-bownd). But if you and your provider decide to try it, you should know what Zepbound side effects to watch for.

In this post, we cover common and serious side effects of Zepbound, including drug interactions and other key details you need to know about Zepbound.

Looking for a caring, attentive medical professional who can help you with a weight loss treatment plan? Find one on Klarity Health. 

Zepbound prescriptions online – same-day consultations

Skip the wait and get a same-day Zepbound prescription online, if medically appropriate. Start your weight loss journey today.

Start your consultation now

The background on Zepbound 

Ozempic and Wegovy (2 different types of semaglutide online prescriptions) are popular for helping with successful weight loss. Both Ozempic and Wegovy have the same active ingredient, semaglutide, and they work in the same way: they’re glucagon-like peptide-1 (GLP-1) receptor agonists.

Zepbound is similar to Mounjaro (tirzepatide) injections, with the same active ingredient, but Zepbound is specifically intended for weight loss, not just managing type 2 diabetes. It also helps people lose more weight and has fewer side effects than Wegovy.

Zepbound is a dual agonist medication, specifically a glucagon-like peptide-1/gastric inhibitory polypeptide (GLP-1/GIP) dual agonist. GLP-1 and GIP are natural hormones that inhibit glucagon secretion and prompt insulin secretion.

Zepbound isn’t a pill. You take it as a subcutaneous injection. People usually give themselves these shots in the fat of their abdomen, thigh, or upper arm.

Zepbound causes weight loss by improving blood sugar control. This increases how full you feel and reduces your appetite so you eat less and lose weight. It also has other benefits like lowering cholesterol and the risk for heart disease.

And Zepbound does work. In clinical trials, people taking Zepbound lost up to 20.9% of their body weight in 72 weeks. 

Zepbound isn’t for cosmetic weight loss, though. It’s U.S. Food and Drug Administration (FDA) approved only for people who, medically, have obesity (a body mass index [BMI] of 30 or more) or are overweight (with a BMI of 27 or more) and at least one weight-related health problem, such as high blood pressure.

Like any medication, Zepbound can cause common and serious side effects that you should know about before you take it. Some people shouldn’t take it all. 

What you should know about Zepbound before using it

When you get a prescription filled at the pharmacy, it comes with a printout or pamphlet called a monograph. The monograph includes information on everything from pharmacological mechanisms to common and serious side effects.

Before you take any medication, you want to understand possible side effects, drug interactions, and more. You can get this in the monograph and by asking your healthcare provider or pharmacist.

Common side effects are also called adverse reactions. If you have any side effects, these are the ones you’re most likely to experience. They’re considered “common” when they affect 1 to 10% of people who take a medication during clinical trials.

Clinical trials are studies that prove a drug is safe and effective and get it FDA-approved before it’s sold to the public. Research trials done after a medication is approved can also reveal side effects. These kinds of trials produce what is called postmarketing data.

The FDA requires drug manufacturers to include side effects on a prescription drug’s label, aka the monograph or medication guide.

When do Zepbound side effects start?

Zepbound side effects may begin after your first dose. Common side effects like nausea, vomiting, and diarrhea may show up early as your body adjusts to the medication’s effects on digestion. Some people report fatigue or headaches within the first week.

As the dose increases, side effects may change. Some may get worse, while others improve over time. Rare but serious issues, like pancreatitis or gallbladder problems, can take weeks or months to show up.

Most side effects go away as your body gets used to the medication. If they last or become severe, talk to your doctor about adjusting your dose.

What are the common side effects of Zepbound?

The most common side effects of Zepbound are shown in Table 1 below

Table 1: Most common side effects of Zepbound in clinical trials.

Other common side effects of Zepbound include:

• Abdominal pain, which might include abdominal discomfort, abdominal pain, pain in the lower abdomen, pain in the upper abdomen, and abdominal tenderness
• Dyspepsia, which is pain or an uncomfortable feeling in the upper middle part of your stomach area and may include bloating, belching, and nausea
• Injection site reactions, such as bruising, injection site erythema (aka a red rash), injection site pruritus (aka itching), injection site pain, and injection site rash
• Fatigue, asthenia (generalized weakness and lack of energy), lethargy (sleepiness), and/or malaise (feeling ill or unwell)
• Hypersensitivity reactions, primarily, but not exclusively, skin reactions or itching
• Belching, also known as eructation
• Hair loss, more often for women than men
• Gastroesophageal reflux disease (GERD), aka acid reflux or heartburn
• Gastroparesis, a painful type of delayed gastric emptying that is caused by weakened or impaired stomach muscles, and that can lead to food staying in the stomach too long
• Flatulence
• Abdominal distension, characterized by your stomach being outwardly swollen
• Dizziness
• Hypotension (low blood pressure), and orthostatic hypotension (a drop in blood pressure when standing)

That list sounds scary, but let’s put it in perspective. Of 2,519 participants in 2 randomized, double-blind, placebo-controlled trials, each taking 5, 10, or 15 milligrams of Zepbound, 25 to 29% had nausea compared to 8% taking a placebo as shown in Table 1. 

On the other end, just 1 to 2% of participants had hypotension compared to 0% taking the placebo. 

Another way to look at side effects is the number of people who dropped out of trials due to adverse events (side effects). For the trials above, less than 7% of people taking Zepbound stopped taking it because the side effects weren’t worth it for them.

By the numbers that’s 4.8% of the 630 people taking 5 milligrams of Zepbound, 6.3% of the 948 taking 10 milligrams, and 6.7% of the 941 taking 15 milligrams or 30, 60, and 63 people respectively. Most stopped taking it due to gastrointestinal side effects. 

It’s important to note that side effects from Zepbound and other weight loss injections are most common when first taking it or increasing your Zepbound/tirzepatide dosage. Side effects are usually mild to moderate and tend to go away after a week or 2 for most people.

Low dose vs high dose: How Zepbound side effects vary​

Side effects depend on the dose. Lower doses may cause milder effects, while higher doses may lead to stronger symptoms.

Zepbound side effects at lower doses

At a low dose, such as 2.5 milligrams, side effects are usually mild to moderate. The most common Zepbound side effects are nausea, diarrhea, and less appetite. Some people may experience mild dizzy or tired. Since the dose is lower, the body adjusts more easily, making digestive issues less common.

Zepbound side effects at higher doses

Side effects may become more noticeable as the dose increases. Zepbound doses can go up to a maximum of 15 milligrams per week. Gastrointestinal symptoms like nausea, vomiting, and constipation may intensify. Some people may develop acid reflux, bloating, or worsening fatigue. Higher doses may carry a greater risk of rare but serious side effects like gallbladder issues or pancreatitis.

If side effects become severe at higher doses, your doctor may recommend slowing down the dose increase or adjusting your treatment plan.

Are there serious side effects of Zebpound?

Serious side effects are possible when taking Zepbound or any medication. But serious side effects aren’t common.

On average they affect less than 10% of people who take a medication in clinical trials. But they can put you in the hospital, lead to permanent damage or disability, cause birth defects, or even be fatal. 

The most common serious side effect seen in clinical trials for Zepbound was hypoglycemia or low blood sugar in patients with type 2 diabetes. 4.2% of people with type 2 diabetes in the trial taking Zepbound experienced hypoglycemia compared to 1.3% taking the placebo. 

The serious side effects that impacted participants in trials also included: 

• Severe stomach problems
• Kidney problems, including acute kidney injury or kidney failure
• Gallbladder problems, including acute gallbladder disease (gallstones) which is characterized by pain in your upper stomach, fever, yellowing of skin or eyes (jaundice), or clay-colored stools
• Inflammation of the pancreas (acute pancreatitis) which is characterized by persistent pain in your upper abdomen with or without vomiting, especially pain that radiates from your stomach to your back. Patients with pancreatitis may have an increase in serum pancreatic amylase concentrations and serum lipase concentrations
• Serious allergic reactions, characterized by swelling in your face, lips, tongue or throat, hoarseness, trouble swallowing, difficulty breathing, a severe rash or itching, fainting, feeling faint or fizzy, or a very rapid heartbeat
• Low blood sugar (hypoglycemia) if you have type 2 diabetes, characterized by light-headedness, sweating, feeling confusing or drowsy, headache, blurry vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability or mood changes, hunger, weakness, or feeling jittery
• Rapid heartbeat of more than 100 beats per minute (sinus tachycardia); patients taking Zepbound in clinical trials had 1 to 3 additional heartbeats per minute
• Vision changes and/or diabetic retinopathy if you have type 2 diabetes
• Depression or suicidal thoughts
• Ileus, or an inability of the intestines to move food waste out of your body

If you take Zepbound and have any of these side effects or associated symptoms — particularly those associated with a severe allergic reaction, cardiac issues, or suicidal thoughts — call 911 immediately. If you have low blood sugar, eat something, but don’t try to relieve serious symptoms alone.

Who shouldn’t take Zepbound?

When the FDA approves a medication, it requires a thorough written overview of its properties, uses, safety, and effectiveness. Called a monograph, the overview educates people about drug interactions and health issues that may make that medication risky for certain people.

According to Zepbound’s monograph, here’s when to avoid Zepbound, and why some people should only take it with caution.

Drug interactions with Zepbound

If you have type 2 diabetes and use insulin or insulin secretagogues such as sulfonylureas to lower your blood glucose, you may be at higher risk of low blood sugar if you also use Zepbound. You may also need to take a smaller dose of Zepbound than the maximum maintenance dose of 15 milligrams. 

If you take any oral medications or even supplements, it’s important to remember that Zepbound slows down how quickly food leaves your stomach. Because of that, it may impact how effective other medications are, especially those that require a specific concentration to work right — for example, the blood thinner warfarin. 

If you’re in your child-bearing years and using oral contraceptives to avoid pregnancy, your doctor may suggest you switch to or add a non-oral contraceptive for 4 weeks after starting Zepbound or increasing your dose. Zepbound can reduce the effectiveness of oral birth control pills.

It’s not a good idea to take Zepbound with other weight loss medications. Don’t take it with any other GLP-1 agonists, including Ozempic, Saxenda, Mounjaro, or Wegovy online prescriptions. Doubling up can increase side effects. 

Be wary of any over-the-counter (OTC) medications for weight loss you take with Zepbound. Clinical trials on Zepbound didn’t study its use with OTC medications for weight loss.

Boxed warning for Zepbound

A boxed warning, formerly known as a black box warning because it’s printed in a black box on a medication label, is the FDA’s strongest warning for a medication and indicates that a medication poses a major risk.

All GLP-1 and GLP-1/GIP receptor agonist medications have a boxed warning, including Zepbound. The warning exists because in animal studies, rats and mice developed thyroid tumors on these medications. It’s not known if humans develop tumors from taking Zepbound.

Even so, if you or a relative has a history of medullary thyroid carcinoma (or MTC, a type of thyroid cancer) or multiple endocrine neoplasia syndrome type 2 (MEN2), make sure you discuss the risk and weigh the pros and cons of taking Zepbound with your healthcare provider.  

Weight loss and pregnancy

There are no formal studies on Zepbound’s use in pregnant women. There’s also no benefit to losing weight during pregnancy. Animal studies suggest a potential risk of birth defects or miscarriage from Zepbound.

If you’re pregnant or planning to become pregnant talk to your healthcare provider. Experts don’t know yet whether women who are breastfeeding transmit Zepbound to their babies in breast milk, so it’s safest not to take it while breastfeeding.

What to tell your doctor before starting Zepbound

Before taking Zepbound, tell your doctor about any medications you use.

Also, let them know if you or a family member has had medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2). These conditions may increase the risk of thyroid tumors.

If you are pregnant, planning to be, or breastfeeding, talk to your doctor. Zepbound may affect the baby, and its safety for nursing infants is unknown.

Tell your doctor if you have digestive issues, as Zepbound may affect how your stomach empties. Mention any other health problems that may interact with the medication.

How do you reduce the side effects of Zepbound?

One of the best ways to minimize side effects is to use Zepbound as directed.

Another tip is to lean into the lifestyle changes your healthcare professional recommends. For example, make sure you follow any recommendations they give you for diet and physical activity.

If you start Zepbound (or another weight loss medication) and you do have some of the common side effects, you may be able to relieve or reduce those symptoms:

• Stay hydrated by drinking more water and other fluids
• Eat smaller meals
• Avoid fatty and spicy foods
• Limit or eliminate alcohol
• Use over-the-counter (OTC) anti-nausea pills, antacids, antigas remedies, and antidiarrheals or laxatives if constipation affects you

You may also fall into the group of people who simply can’t tolerate Zepbound side effects. In that case, you and your healthcare provider can decide if stopping it, adjusting your dose of Zepbound, or trying something else is the right plan for you.

When to stop Zepbound and seek help

You should stop Zepbound and seek medical attention if you experience:

• Severe nausea, vomiting, or dehydration that prevents you from keeping fluids down.
• Persistent stomach pain, especially if it radiates to your back, could signal pancreatitis.
• Signs of gallbladder issues, such as intense upper-right abdominal pain, fever, or yellowing skin.
• Severe allergic reactions, including swelling of the face, lips, or throat, or difficulty breathing.
• Depression or suicidal thoughts, as mood changes can be a rare but serious side effect.

For mild to moderate side effects, your doctor might recommend changing your dose or adding in supportive treatments, like changing your diet or eating smaller meals. If you notice any red flags, stop the medication and seek medical care.

Patient experiences of Zepbound 

Zepbound has an average rating of 8.9 out of 10 on Drugs.com from 246 weight loss reviews. At the time of publication, 86% had positive results, while 1% reported a negative experience.

Drugs.com reviewers noticed fewer cravings after the first dose and weight loss within two weeks. Some experienced Zepbound side effects like nausea, vomiting, and gas, often when increasing the dose. These symptoms usually improve over time. To reduce side effects, users recommend eating less when starting Zepbound.

Key takeaways

Zepbound can have side effects. Most people who have side effects have nausea, diarrhea, vomiting, or constipation, which can sometimes be managed with OTC medications and dietary adjustments, but other side effects do happen.

Common side effects are most likely when first starting Zepbound or increasing your dose. Most Zepbound side effects diminish or go away in a week or 2.

Serious side effects can result from taking Zepbound. If you take it, contact your provider or call 911 if you have any serious symptoms. 

You should take Zepbound with caution if you take certain medications or have type 2 diabetes.

To make sure Zepbound is safe and effective for you, talk to your healthcare provider and/or your pharmacist about the potential side effects and how to recognize and manage them. Make and keep regular follow-up appointments for monitoring while on Zepbound.

Connect with a weight loss provider on Klarity Health

Klarity Health connects people just like you with independent healthcare professionals who specialize in weight management. Your provider can help you decide if Zepbound is right for you. Find a weight loss provider and start losing weight soon.