FDA approves Zepbound (tirzepatide) for chronic weight management

The FDA approved Zepbound (tirzepatide) on Nov. 8, 2023, for chronic weight management in adults with obesity, or adults who are overweight and have at least one weight-related medical condition ^[1]. It is the same molecule Eli Lilly sells as Mounjaro for type 2 diabetes, and it is the second drug in a highly effective class of weight loss medicines to reach the U.S. market ^[2].

The label covers adults with a body mass index of 30 kg/m2 or higher, or a BMI of 27 kg/m2 or higher along with a condition such as hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea or cardiovascular disease ^[1]. It is meant to be used with a reduced-calorie diet and increased physical activity ^[1]. The label says it should not be used with other tirzepatide-containing products or with any GLP-1 receptor agonist medicine ^[1]. Zepbound activates both GIP and GLP-1 hormone receptors, which Lilly describes as a first among approved obesity treatments ^[1].

Approval was based on the phase 3 SURMOUNT-1 and SURMOUNT-2 trials ^[1]. In SURMOUNT-1, 2,539 adults with obesity or excess weight and weight-related medical problems, but not diabetes, received the drug or a placebo for 72 weeks ^[1]. At the highest dose of 15 mg, people lost an average of 48 lb; at the lowest dose of 5 mg, they lost an average of 34 lb, compared with 7 lb on placebo ^[1]. The average starting weight was 231 lb ^[1]. About 1 in 3 people at the highest dose lost more than 58 lb, or 25% of body weight, compared with 1.5% of those on placebo, a figure Lilly notes was not controlled for type 1 error ^[1]. The trial also recorded changes in cholesterol and reductions in blood pressure and waist size, though Zepbound is not approved to treat those conditions ^[1]. The broader SURMOUNT program has enrolled more than 5,000 people across six registration studies ^[1].

Zepbound is expected in U.S. pharmacies by the end of the year in six doses: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg and 15 mg, the same dose range used for Mounjaro ^[1][2]. The list price is $1,059.87 a month, which Lilly says is about 20% lower than Wegovy (semaglutide 2.4 mg) for weight loss ^[1]. List price is not the same as what patients typically pay once insurance and discounts are applied ^[1]. Lilly is also offering a savings card: people with commercial insurance that covers Zepbound may pay as little as $25 for a one-month or three-month prescription, and people with commercial insurance that does not cover it may pay as little as $550 for a one-month prescription, roughly half the list price ^[1]. The card program begins in the days after the drug reaches pharmacies ^[1].

Zepbound carries a boxed warning about thyroid C-cell tumors ^[1]. It is not for people with a personal or family history of medullary thyroid carcinoma, people with Multiple Endocrine Neoplasia syndrome type 2, or people who have had a serious allergic reaction to tirzepatide or the other ingredients ^[1]. The most commonly reported side effects, seen in at least 5% of trial participants, were nausea, diarrhea, vomiting, constipation, abdominal pain, indigestion, injection-site reactions, fatigue, allergic reactions, belching, hair loss and heartburn ^[1]. Gastrointestinal side effects were more common than with placebo, and more people taking Zepbound stopped treatment because of them ^[1]. The drug has not been studied in people with a history of pancreatitis or severe gastrointestinal disease, including severe gastroparesis, and it is not known whether it is safe and effective in children under 18 ^[1].

John Sharretts, director of the Division of Diabetes, Lipid Disorders and Obesity in the FDA's Center for Drug Evaluation and Research, said in a statement that with rising rates of obesity and overweight in the United States, the approval "addresses an unmet medical need" ^[2]. The decision also adds competition for Novo Nordisk, which has had to limit starter doses of Wegovy because of ongoing shortages ^[2].

Why it matters for patients

For adults who meet the BMI criteria, there is now a second approved option in the same drug class, which may matter to people who have struggled to start or stay on Wegovy during its supply limits ^[2]. The two drugs have not been compared directly in a head-to-head trial; Zepbound's approval rests on trials against placebo ^[1]. Whether employers and insurers will cover Zepbound, and at what copay, has not been disclosed, and the savings card has terms and conditions ^[1]. The drug is prescription-only and is not for everyone: people with a personal or family history of medullary thyroid carcinoma or with MEN 2 should not use it ^[1].

What happens next

Lilly expects Zepbound in U.S. pharmacies by the end of 2023 ^[1]. The savings card program opens in the days after that ^[1]. Tirzepatide is also under regulatory review for weight management in Europe, China, the United Kingdom and several additional markets ^[1].