Zepbound side effects from A to Z and everything in between

Ozempic (semaglutide), Wegovy (semaglutide), and Mounjaro (tirzepatide) are popular for their weight loss success. But, there’s a “newer” medication in town — Zepbound (tirzepatide). It helps people lose more weight and has fewer side effects than Wegovy. Nonetheless, if you and your provider decide to try Zepbound, you should know what Zepbound side effects to watch for.

We cover common and serious side effects, drug interactions, and more here, along with what you need to know about Zepbound side effects. 

The background on Zepbound 

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 the secretion of insulin. Put simply, the work in Zepbound for weight loss by improving blood sugar control, increasing how full you feel, and reducing appetite, so you eat less and lose weight.

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 are medically obese (have a body mass index [BMI] of 30 or more) or medically overweight with a BMI of 27 or more and at least one weight-related health problem. And it should be used with a reduced-calorie diet and increased physical activity.

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 qualifies as a common side effect

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

Common side effects are also called adverse reactions. They’re considered “common” when they affect 1 and 10% of people who take a medication during clinical trials. Clinical trials are the studies done to prove a drug is safe and effective and get it FDA-approved before it’s sold to the public. Side effects may also come from research trials done after a medication is approved, called postmarketing data.

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

What are the common side effects of Zepbound?

The common side effects of Zepbound are the ones that affect 1 to 10% of people who took it in clinical trials. The most common side effects of Zepbound are shown in Table 1.

Other common side effects of Zepbound experienced by less than 10% of trial participants taking 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, aka eructation
• Hair loss, more often for women than men
• Gastroesophageal reflux disease, aka acid reflux or heartburn
• Flatulence
• Abdominal distension, characterized by your stomach being outwardly swollen
• Dizziness
• Hypotension, decreased 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, of those 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 taking 5, 10, or 15 milligrams of Zepbound 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/tirzetpatide dosage. Side effects are also usually mild to moderate and tend to diminish or go away after a week or 2 for most people.

What to do about common Zepbound side effects?

If you start Zepbound (or another weight loss medication with similar side effects), and you do have common side effects, you may be able to relieve or reduce symptoms by:

• Staying hydrated by drinking more water and other fluids
• Eating smaller meals
• Avoiding fatty and spicy foods
• Limiting or eliminating alcohol
• Using 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, or trying something else is the right plan for you.

Are there serious side effects of Zepbound?

There are serious side effects (aka serious adverse events) that can happen when taking Zepbound or any medication. Serious side effects tend to be uncommon and on average affect less than 1% of people who take a medication in clinical trials. Nonetheless, they can put you in 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 in the trial with type 2 diabetes taking Zepbound experienced hypoglycemia compared to 1.3% taking the placebo. 

The serious side effects that impacted participants in trials include: 

• Severe stomach problems
• Kidney problems, including acute kidney injury or kidney failure, which can result from diarrhea, nausea, and vomiting causing dehydration
• 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 your pancreas (acute pancreatitis) which is characterized by persistent pain in your upper stomach with or without vomiting, especially pain that radiates from your stomach to your back. Patients with pancreatitis taking Zepbound may have an increase in serum pancreatic amylase concentrations and serum lipase concentrations, the significance of this increase is unknown in the absence of pancreatitis
• Serious allergic reactions, such as swelling of your face, lips, tongue or throat, trouble breathing or swallowing, 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 feeling dizzy or light-headed, 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, contact your healthcare provider or call 911 immediately. If you have low blood sugar, eat something, otherwise, don’t try and relieve serious symptoms on your own. 

What else to know about taking Zepbound

When the FDA approves a medication, it requires the monograph warn people about drug interactions and health issues that may make a medication riskier for certain people. Here’s the rundown of when to avoid Zepbound or to take it only with caution.

Drug interactions with Zepbound

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

If you take any oral medication, it’s important to know that because Zepbound slows down how quickly food leaves your stomach, it may impact the effectiveness of a medication that requires 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 contraceptives.

It’s not a good idea to take Zepbound with other weight loss medications. Don’t take it with another GLP-1 agonist, including Ozempic, Wegovy, Mounjaro, or Saxenda. 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. Nonetheless, if you or a relative has a history of medullary thyroid carcinoma (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.

Zepbound side effects: how bad are they?

Yes, Zepbound has side effects, some of which can be serious and you should use it with caution and only after a thorough conversation with your healthcare provider.  But, in clinical trials, fewer people stopped Zepbound due to side effects compared to those in a Wegovy trial. 

And Zepbound is also effective in helping people lose weight. In trials, people lost up to 20.9% of their body weight in 72 weeks. People who needed to lose weight for health reasons. That’s more body weight than people lost in Wegovy trials, which was 14.8% in 68 weeks.

Reviews on Zepbound also indicate that people taking it are generally happy with the experience.

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 and tend to 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. And have regular follow-up appointments and monitoring while on Zepbound.

Connect with a weight loss provider on Klarity 

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

Sources

• Reuters, Lilly weight-loss drug Zepbound new US prescriptions surpass Wegovy for first time, Mar. 2024, https://www.reuters.com/business/healthcare-pharmaceuticals/lilly-weight-loss-drug-zepbound-new-us-prescriptions-surpass-wegovy-first-time-2024-03-15/
• PainScale, How Are Common Side Effects and Rare Side Effects Defined?, https://www.painscale.com/article/how-are-common-side-effects-and-rare-side-effects-defined
• DailyMed, LABEL: ZEPBOUND- tirzepatide injection, solution, Nov. 2023, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b
• Drugs.com, How often do side effects occur, ranging from common to rare?, Feb. 2023, https://www.drugs.com/medical-answers/how-often-side-effects-occur-ranging-very-common-3576518/
• Nature Medicine, Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial, Oct. 2023, https://www.nature.com/articles/s41591-023-02597-w 
• The New England Journal of Medicine, Once-Weekly Semaglutide in Adults with Overweight or Obesity, Feb. 2021, https://www.nejm.org/doi/full/10.1056/NEJMoa2032183

The information provided in this article is for educational purposes only and should not be construed as medical advice. Always seek the guidance of a qualified healthcare professional with any questions or concerns you have regarding your health.

How we reviewed this article: This article goes through rigorous fact-checking by a team of medical reviewers. Reviewers are trained medical professionals who ensure each article contains the most up-to-date information, and that medical details have been correctly interpreted by the author.