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

Good news for those with a prescription for Wegovy or Ozempic for weight loss and trouble getting the medication because of shortages: there’s a new weight loss drug in town. Zepbound is the brand name of tirzepatide, 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. The promising drug may provide much-needed relief in a market where demand has outpaced supply. 

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Weight loss claims apply to branded medications. Limited availability of some doses of Zepbound. See Important Safety Information

Zepbound is an injectable prescription medication that is FDA-approved for weight loss in people with obesity or with 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. By 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. 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. 

Weight loss results appear to be dose-dependent with Zepbound, with people taking higher dosage strengths losing 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 34%. That data makes Zepbound the most effective weight loss medication on the market, for now, leading to more weight loss, on average, than either Wegovy, Saxenda, or Ozempic, similar injectable medications that are in the same drug class as Zepbound. 

In addition to weight loss, there were 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.

Yes and no. Yes, in the sense that Mounjaro and Zepbound are two brand-name versions of the same active ingredient, tirzepatide. No, in the sense that Zepbound and Mounjaro are FDA-approved to treat different conditions. The Zepbound/Mounjaro distinction is similar to Wegovy and Ozempic or Saxenda and Victoza. Each pair of drugs shares the same active ingredient (semaglutide for Wegovy and Ozempic, liraglutide for Saxenda and Victoza), but the drug makers have created different brand names to reflect the different conditions they treat.

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 with overweight and a health-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 but not type 2 diabetes. Both Mounjaro and Zepbound should be used in combination with lifestyle changes like diet and exercise.

Zepbound works similarly to other injectable weight loss medications, like Wegovy and Saxenda, but there’s one big difference. These medications are known as GLP-1 (glucagon-like peptide 1) receptor agonists 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.

What sets Zepbound apart from Wegovy and Saxenda and makes it particularly effective for weight loss is that it targets not just the GLP-1 receptor but also the 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 and making it so that people only have to inject Zepbound once a week.

GLP-1 agonists and GLP-1/GIP agonists help with weight loss by slowing down digestion. Specifically, they keep food in your stomach longer, which leads you to feel full sooner and stop eating. At the same time, GLP-1 drugs further reduce appetite by sending signals to your brain telling you 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 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 will be 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 (fever or rash) 

• Fatigue

• Belching

• Hair loss

• Gastroesophageal reflux disease (GERD)

Many of these side effects — particularly the digestive ones 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 escalating 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 dosage of insulin to avoid hypoglycemia or recommend other safety measures to avoid potential side effects.

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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 these medications, although that may change in the future. 

Is Zepbound a good option for you? It could be, especially if you have been struggling to lose weight with diet and exercise alone. If you’re interested in Zepbound, set up 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

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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

January 03, 2024

Written by

Amelia Willson

Fact checked by

Yael Cooperman, MD

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About the medical reviewer

Yael Cooperman, MD, Ro

Yael Cooperman is a physician and works as a Senior Manager, Medical Content & Education at Ro.