Zepbound side effects: common, serious, interactions, and more

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.

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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.

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.

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.

Does Zepbound have long-term side effects?

How long do Zepbound side effects last? Most people notice Zepbound side effects when they first start taking it, and then feel relief as time passes. But some people have more lasting side effects.

It is possible to experience kidney problems including long-term kidney damage from taking Zepbound. Zepbound can also cause thyroid issues and may increase your risk for thyroid tumors and thyroid cancer — although the research is still ongoing.

It’s so important not to take Zepbound without being monitored by a healthcare professional who knows both your case and the latest research on Zepbound side effects you might experience — both long- and short-term.

You can also compare other prescription medications to treat overweight and obesity based on their side effect profiles and your case. The side effects from an Ozempic online prescription, for example, might affect you less than Zepbound side effects.

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.

Zepbound side effects: how bad are they?

Yes, Zepbound has side effects, some of which can be serious. 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. 

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

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

Manage side effects with the proper use of Zepbound

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.

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.