What to know about Zepbound, Eli Lilly’s new weight loss drug

If you’re on a weight loss journey, you’ve likely heard of Ozempic and Wegovy. But there’s also a newer weight loss drug in town. Zepbound, the brand name of tirzepatide, is a medication that was previously only marketed under the brand name Mounjaro. 

Zepbound is approved by the FDA for chronic weight management in people with obesity and overweight. Zepbound, like other weight loss medications, is also in shortage, but certain dosages are more available than others. At the time of writing, the 2.5 mg dosage is not in shortage.

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Zepbound is an FDA-approved injectable prescription medication for weight loss in people with obesity or overweight and a weight-related health condition. In clinical trials, Zepbound led to an average weight loss of 15%–21% within a year and a half, when used in combination with diet and exercise. In that time period, participants taking Zepbound lost between 35–52 pounds. In comparison, those taking a placebo lost just five pounds on average.

Each box of Zepbound contains four single-dose prescription pens. To take Zepbound, you inject the medication just under the skin of your abdomen, thigh, or upper arm once a week. You should rotate your injection site each time you inject. The medication is available in six dosage strengths. Typically, health providers recommend starting with a low 2.5 milligrams (mg) dosage of Zepbound weekly before increasing the dosage by 2.5 mg every four weeks until a maintenance dosage of 5 mg, 10 mg, or 15 mg is reached. 

Zepbound works similarly to other injectable weight loss medications, like Wegovy and Ozempic, but there’s one big difference. Wegovy and Ozempic are known as GLP-1 agonists (glucagon-like peptide 1) because they target the receptor of GLP-1, a gut hormone produced naturally in the body. GLP-1 plays a role in regulating both appetite and blood sugar levels in response to food.

GLP-1 agonists help with weight loss by slowing down digestion. Specifically, they keep food in your stomach longer, so you feel full sooner and stop eating. GLP-1 drugs further reduce appetite by sending signals to your brain that you are full. Some research suggests that these medications may even affect your brain’s reward system regarding food and may reduce your cravings for certain foods.

Zepbound is particularly effective for weight loss because it targets the GLP-1 receptor and another receptor for glucose-dependent insulinotropic polypeptide (GIP). This distinction may explain Zepbound’s more pronounced effects on weight loss and metabolism. In the body, GLP-1 and GIP only remain active for a few minutes. But tirzepatide, the active ingredient in Zepbound, remains active for days, amplifying the effects of GLP-1 and GIP. This also means people only have to inject Zepbound once a week (a welcome alternative to daily injections).

GIP (glucose-dependent insulinotropic polypeptide) is a hormone released by the gut when you eat. The hormone regulates your blood sugar levels, particularly when you consume carbohydrates and fats. In this process, GIP helps your body absorb and use sugar by telling your pancreas to release insulin. It also prevents the liver from producing too much sugar.

While Zepbound may increase weight loss by regulating blood sugar, it’s important to understand that the medication alone is not enough to produce significant weight loss results. To be effective, Zepbound should be used along with a healthy diet and consistent exercise.

Weight loss results appear to be dose-dependent with Zepbound. People taking higher dosage strengths lose more weight. For example, in clinical trials, people taking:

• 5 mg of Zepbound lost 15% of their body weight (35.5 pounds), on average

• 10 mg of Zepbound lost 19.5% of their body weight (49 pounds), on average

• 15 mg of Zepbound lost 20.9% of their body weight (52 pounds), on average

In clinical trials, 85%–91% of people taking Zepbound lost at least 5% of their body weight. Over half of people taking the 10 mg or 15 mg dosage lost at least 20% of their body weight. And among those taking the highest 15 mg dosage of Zepbound, one in three lost 25% of their body weight. Overall, people shaved an average of 5.5–7.3 inches off their waistlines, reducing their body fat by about 34%. That data makes Zepbound the most effective weight loss medication on the market, leading to more weight loss, on average, than either Wegovy, Saxenda, or Ozempic, similar injectable medications in a similar class as Zepbound. 

In addition to weight loss, clinical participants saw other health benefits in connection with the weight loss. Participants’ blood pressure and cholesterol also improved on Zepbound. Nearly all (95%) of those who had prediabetes at the beginning of the study had normal blood sugar levels by the end of the trial. 

Mounjaro and Zepbound are two brand-name versions of the same active ingredient, tirzepatide. However, Zepbound and Mounjaro are FDA-approved to treat different conditions. 

Mounjaro came first and is FDA-approved to treat type 2 diabetes in adults by controlling their blood sugar levels. Zepbound is FDA-approved for chronic weight management in adults with obesity or overweight and a weight-related medical condition. Prior to Zepbound’s approval, healthcare providers may have prescribed Mounjaro off-label for weight loss to patients with overweight or obesity who may not have had type 2 diabetes. Both Mounjaro and Zepbound should be used in combination with lifestyle changes like diet and exercise.

Zepbound is FDA-approved for chronic weight management in adults who meet one of the following criteria: 

• Body mass index, or BMI, of 30 or higher (defined as obesity)

• BMI of 27 or higher with a weight-related health condition, such as high blood pressure, high cholesterol, type 2 diabetes, obstructive sleep apnea, or heart disease

Before prescribing Zepbound, your healthcare provider will ask you about your personal and family medical history and a list of any medications or supplements you are currently taking. This is to ensure Zepbound is safe for you, as people with certain health conditions may be at increased risk when taking Zepbound. For example, Zepbound should not be used by people who are pregnant, breastfeeding, or planning to be anytime soon. Zepbound is also contraindicated in people with severe gastrointestinal disease.

Also, animal studies have found that tirzepatide, the active ingredient in Zepbound, increases the risk of thyroid tumors in rats. While it is not known if Zepbound has the same effect in humans, people who have a personal or family history of certain thyroid cancers, including medullary thyroid carcinoma and Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), should not take Zepbound.

The most common side effects of Zepbound include:

• Nausea

• Diarrhea

• Vomiting

• Constipation

• Abdominal pain

• Indigestion

• Injection site reactions (such as rash) 

• Fatigue

• Belching

• Hair loss

• Gastroesophageal reflux disease (GERD)

Many of these side effects — particularly the digestive effects like nausea, diarrhea, and constipation — are common to medications like Zepbound, Mounjaro, Ozempic, Wegovy, and others. Typically, gastrointestinal side effects range from mild to moderate and are most common when increasing your dose.

For many people, Zepbound is a safe and effective medication for weight loss. In rare cases, however, it may cause serious side effects. These include:

• Severe gastrointestinal disease

• Acute kidney injury

• Acute gallbladder disease

• Acute pancreatitis

• Allergic reaction to Zepbound

• Hypoglycemia (low blood sugar)

• Diabetic retinopathy (vision loss or damage in people with type 2 diabetes)

• Depression or suicidal thoughts

People with type 2 diabetes or a history of kidney or gallbladder problems may be at increased risk of experiencing these side effects, so be sure to tell your healthcare provider about any underlying health conditions prior to starting Zepbound. They can adjust your dosages of insulin to avoid hypoglycemia or recommend other safety measures to avoid potential side effects.

Eli Lilly, the maker of Zepbound, has set the list price for a one-month supply of Zepbound at about $1,060, which is about 20% less than the cost of Wegovy. The actual cost of Zepbound you pay may be higher or lower, depending on your insurance coverage and the pharmacy you use. 

Eli Lilly offers a Zepbound Savings Card for people with commercial insurance. This coupon brings the cost of a 1- or 3-month supply of Zepbound down to as low as $25 for those with coverage for Zepbound, or $550 for those with insurance but no coverage for Zepbound. Medicare notably does not provide coverage for weight loss medications, although that may change in the future. 

If you struggle to lose weight with diet and exercise alone, Zepbound may be a good option for you. To learn more about Zepbound, make an appointment with your health provider or connect with one of our telehealth providers through the Ro Body program, a comprehensive, 12-month weight loss program that includes:

• Metabolic testing (if needed) 

• A personalized treatment plan

• 1:1 health coaching

• A step-by-step curriculum

• Ongoing support from your provider

• Insurance concierge services to help you get coverage

Your provider will help you develop a safe and effective weight loss plan.

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How we reviewed this article

Every article on Health Guide goes through rigorous fact-checking by our team of medical reviewers. Our 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 writer.

Current version

May 14, 2024

Written by

Amelia Willson

Fact checked by

Raagini Yedidi, MD

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About the medical reviewer

Raagini Yedidi, MD

Raagini Yedidi, MD, is an internal medicine resident and medical reviewer for Ro.