Zepbound (tirzepatide) is a prescription weight loss medicine. It contains tirzepatide, the same active ingredient as the type 2 diabetes medicine Mounjaro. The FDA approved Zepbound in 2023 to help adult people with excess weight or obesity lose weight and keep it off, especially those who also have other health conditions affected by excess weight, such as high blood pressure, type 2 diabetes, and heart disease. Zepbound is usually injected once weekly, along with eating fewer calories and being more physically active. It comes in a ready-to-use pen for home injections.
How Does Zepbound Reduce Weight?
Tirzepatide works by activating two proteins called glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) which belong to a group of hormones called incretins. Incretins are naturally produced by the intestine (gut) as soon as food enters your body and stimulate the production of insulin, a hormone that helps digest sugar.
GLP-1 also helps control your appetite by working in your brain and slows down the movement of food through your stomach. This makes you feel full faster and stay full longer after eating. As a result, you may eat less and lose weight.
Is It Right for Me?
Zepbound may be the right choice for you if:
- You have obesity.
- You have excess weight and other health problems because of it. Some examples of health problems related to excess weight are hypertension (high blood pressure), dyslipidemia (high levels of fat, including cholesterol and triglycerides, in the blood), type 2 diabetes, apnea (when breathing pauses repeatedly during sleep), and heart disease.
Your health care provider will measure your weight and height and calculate your body mass index (BMI) by dividing your weight (in kilograms) by your height (in meters) squared. If your BMI is 27 or more, you have excess weight. If your BMI is 30 or more, you have obesity. Your doctor will also examine you and review your medical history to decide if Zepbound is right for you.
How Was It Studied for Weight Loss?
Two clinical studies, SURMOUNT-1 and SURMOUNT-2, were done to see the benefits and risks of Zepbound for weight loss in adult people with excess weight. The first study, SURMOUNT-1, was done in people without diabetes, and the second, SURMOUNT-2 , was done in people with type 2 diabetes.
The main questions these studies wanted to answer were:
- How much does body weight change in people who get Zepbound?
- How many people will lose at least 5% of their body weight after getting Zepbound?
To learn this, researchers measured the weight of the people in each study at the start and at the end of the study.
What medicines did the people in the study take?
People in both studies were randomly selected to get either Zepbound injection or placebo. The placebo looked like Zepbound but didn’t contain any medicine. Neither the people in the study nor the doctors knew who got Zepbound or placebo.
Both people who got Zepbound and those who got placebo had regular sessions with a diet expert to guide them with a healthy diet and exercise throughout the study.
Who was in the studies?
To take part in each study, people had to:
- Be at least 18 years old (adult)
- Have obesity (a BMI of 30 or more) or excess weight (a BMI of 27 or more) and at least one health problem related to excess weight.
- Have tried to lose weight through dieting once or twice.
In addition, people who took part in the second study, SURMOUNT-2, also had to have type 2 diabetes with a glycated hemoglobin (HbA1c) of at least 7% (53 mmol/mol) but no more than 10% (86 mmol/mol). HbA1c is a protein in your blood that is tested to evaluate your level of blood sugar control.
Who was excluded from the studies?
People could not be in either study if they had experienced a weight change of more than 5 kilograms (about 11 pounds) in the 3 months before the study, had undergone or planned to undergo surgery to treat obesity, had gotten weight loss medicines in the 3 months before the study, had a history of inflammation of the pancreas (pancreatitis), or had certain types of thyroid or other cancers.
In addition:
- People with diabetes could not be in the SURMOUNT-1 study.
- People with type 1 diabetes or those who had certain eye diseases caused by diabetes could not be in the SURMOUNT-2 study.
- People who had gotten injectable medicines for type 2 diabetes in the 3 months before the study could not be in the study on people with type 2 diabetes.
What were the study populations?
- A total of 2,539 people took part in the SURMOUNT-1 study and 938 in the SURMOUNT-2 study.
- Of those, 2,519 people got Zepbound and 958 got placebo.
- All the people in the SURMOUNT-2 study had type 2 diabetes.
- The age range across both studies was from 18 to 85.
- A total of 37% of the people in both studies were men.
- About 72% of the people in both studies were White, 12% Asian, 8% Black or African American, 7% American Indian or Alaska Native, and 51% identified as Hispanic or Latino ethnicity.
- The average BMI of the people in both studies was 37.4, with 29% having a BMI of 40 or more.
- About 41% of people in both studies had high blood pressure (hypertension), 37% had high levels of fat in the blood (dyslipidemia), 25% had type 2 diabetes, 7% experienced pauses in breathing during sleep (apnea), and 4% had heart disease.
How long was the study?
Each study lasted 72 weeks (about 1 year and 5 months).
What Were the Main Benefits of Zepbound Seen in Studies?
In both studies, people who got Zepbound lost significantly more weight than those who got a placebo. In addition, significantly more people who got Zepbound lost 5% or more of their weight compared to those who got a placebo. Weight loss with Zepbound was not affected by age, sex, race, ethnicity, starting BMI, or blood sugar levels.
The SURMOUNT-1 study compared three different doses of Zepbound (5 milligrams, 10 milligrams, and 15 milligrams) to a placebo. The table below shows the percentage of people who lost different amounts of weight while taking different doses of Zepbound or a placebo.
| Amount of Weight Lost | Zepbound 5 mg | Zepbound 10 mg | Zepbound 15 mg | Placebo |
| At least 5% weight loss | 85% | 89% | 91% | 35% |
| At least 10% weight loss | 69% | 78% | 84% | 19% |
| At least 15% weight loss | 48% | 67% | 71% | 9% |
| At least 20% weight loss | 30% | 50% | 57% | 3% |
The SURMOUNT-2 study compared two different doses of Zepbound (10 milligrams and 15 milligrams) to placebo. The table below shows the percentage of people who lost different amounts of weight while taking different doses of Zepbound or a placebo.
| Amount of Weight Lost | Zepbound 10 mg | Zepbound 15 mg | Placebo |
| At least 5% weight loss | 79% | 83% | 33% |
| At least 10% weight loss | 61% | 65% | 10% |
| At least 15% weight loss | 40% | 48% | 3% |
| At least 20% weight loss | 22% | 31% | 1% |
What Are the Side Effects of Zepbound, and How Can I Prevent or Manage Them?
The most common side effects of Zepbound include nausea, diarrhea, vomiting, constipation, stomach (abdominal) pain, indigestion, injection site reactions (skin sensitivity where the injection goes in your skin), feeling tired, allergic reactions, belching, hair loss, and heartburn.
Digestive system: To help with nausea, diarrhea, constipation, indigestion, or heartburn, try:
- Adding fruits and vegetables to your diet
- Dividing your daily meals in multiple smaller portions
- Staying away from greasy or heavy meals that are difficult to digest
Dehydration: Not having enough water in your body (dehydration) can cause, or worsen, kidney problems, especially if you also take other medications that increase water loss such as diuretics (water pills). Some signs of dehydration include dry mouth, excessive thirst, and dizziness.
To help avoid dehydration:
- Make sure to drink lots of fluids to stay hydrated throughout the day, especially if you have nausea or diarrhea, or you vomit.
- Stay away from drinking large amounts of coffee and alcohol while you are on Zepbound.
Gallbladder: Zepbound can cause gallbladder problems such as gallstones or gallbladder inflammation.
- Tell your doctor if you have nausea, notice yellowing of your skin or eyes, or experience severe stomach pain.
- Stay away from greasy food to help avoid gallbladder problems.
Vision changes: If you have type 2 diabetes, tell your health care providers if you notice any change in your vision while you are on Zepbound.
Mood changes: Be aware of changes in your mood and mental state. Inform your health care providers if you have unusually negative feelings or thoughts that worry you.
What are the serious side effects of Zepbound, and how can I prevent or manage them?
In addition to common side effects, Zepbound may cause serious side effects:
- Risk of thyroid cancer. Inform your doctor if you notice a lump or swelling in your neck, have raspy or low voice (hoarseness), trouble swallowing, or shortness of breath. These could be the symptoms of thyroid cancer. In studies done on animals, Zepbound has caused thyroid tumors and cancers, but it is not known if it could have the same effect in people.
Do not use Zepbound if you or anyone in your family has a history of a type of thyroid cancer called medullary thyroid carcinoma, or if you have multiple endocrine neoplasia syndrome type 2 (MEN 2).
How Do I Know if Zepbound Is Working?
You may start noticing changes in your weight after a few weeks. Your doctor will check your progress during regular visits and may change your dose of Zepbound to suit your individual needs. Do not change your dose or stop Zepbound unless your health care provider tells you.
How Do Other Medicines Interact With Zepbound?
Inform your health care provider and pharmacist about all the other prescription and over-the-counter medicines, vitamins, supplements, and herbal products you take. Zepbound lowers your blood sugar. It can also affect how some medicines work in your body.
Insulin or medicines that raise insulin levels in the body: These medicines lower blood sugar in people with type 2 diabetes. When your doctor starts you on Zepbound, they may adjust the dose of these medicines to help prevent blood sugar from dropping too much (hypoglycemia). Examples include: chlorpropamide, glimepiride, glipizide, glyburide, nateglinide, repaglinide, tolazamide, and tolbutamide.
Medicines taken by mouth: Zepbound slows down the movement of your stomach. As a result, medicines may take longer to pass into your bloodstream and they may become less effective. This is especially important for medicines like some blood thinners and birth control pills. Your doctor will monitor you closely and advise you on how to best handle this.
How Can I Get Zepbound?
You will need a prescription for Zepbound from a health care provider, and you can get it at any pharmacy.
If you need support paying for Zepbound and have certain types of commercial insurance, you may be eligible for the Zepbound Savings Card Program offered by the manufacturer for a limited time. Visit zepbound.lilly.com/coverage-savings to learn more.
