Tirzepatide Approved by FDA for Chronic Weight Management in Adults

The US Food and Drug Administration (FDA) on Wednesday approved tirzepatide for use in adults requiring chronic weight management. Manufacturer Eli Lilly expects the drug, to be marketed as Zepbound, to be available to patients by the end of this year, according to a company statement.¹

Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) hormone mimetic, is administered subcutaneously once weekly and is indicated as an adjunct to a reduced calorie diet and increased physical exercise for adults with obesity or overweight and at least 1 weight-related condition.¹ A first-in-class agent, tirzepatide was previously granted FDA priority review and fast track designation for chronic weight management. The drug was approved in 2022 (as Mounjaro) for the treatment of hyperglycemia in adults with type 2 diabetes.

“Obesity and overweight are serious conditions that can be associated with some of the leading causes of death such as heart disease, stroke and diabetes,” said John Sharretts, MD, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research.¹ “In light of increasing rates of both obesity and overweight in the United States, today’s approval addresses an unmet medical need.”

SURMOUNT clinical program

The FDA based its approval on findings from 2 phase 3 randomized placebo-controlled clinical trials, SURMOUNT-1 and SURMOUNT-2, which each ran for 72 weeks. The SURMOUNT phase 3 global clinical development program for tirzepatide for chronic weight management began in late 2019, enrolling more than 5000 participants across 6 registration studies.

In the SURMOUNT-1 trial, investigators compared tirzepatide vs placebo in 2539 adults with obesity or overweight plus one weight-related medical problem, excluding type 2 diabetes (T2D). At 72 weeks, participants taking the highest dose of 15 mg lost an average of 48 lbs; those taking the lowest dose of 5 mg lost an average of 34 lbs, compared with a loss of 7 lbs in the placebo group. Half of participants receiving 10 mg and 47% of those receiving 15 mg of tirzepatide lost 20% or more of their baseline body weight compared with 3% in those receiving placebo. SURMOUNT-1 participants had an average baseline weight of 231 lbs and average BMI 38 kg/m²; weight loss at all 3 dose levels was statistically significant.

The SURMOUNT-2 investigators randomly assigned 938 adults with obesity or overweight who also had T2D to receive tirzepatide 10 or 15 mg or placebo. They reported average baseline weight among the cohort of 222 lbs and BMI of 36 kg/m². Investigators reported mean weight changes among tirzepatide-treated participants of -13.4% for those receiving 10 mg and of -15.7% for those on 15 mg compared to a change of -3.3% in participants receiving placebo.

“Unfortunately, despite scientific evidence to the contrary, obesity is often seen as a lifestyle choice—something that people should manage themselves,” said Leonard Glass, senior vice president of global medical affairs at Lilly Diabetes and Obesity.¹ Although diet and exercise have been common weight loss strategies for decades, “it is not uncommon for a person to have tried 20 to 30 times to lose weight with this approach,” he added. “Research now shows that the body may respond to a calorie-deficit diet by increasing hunger and reducing feelings of fullness, making weight loss more difficult.”¹

Common adverse events, which are typical of the GLP-1 receptor agonist class, included nausea, diarrhea, vomiting, constipation, abdominal pain, dyspepsia, injection-site reactions, fatigue, hypersensitivity reactions, burping, hair loss, and gastroesophageal reflux disease. Most gastrointestinal adverse events occurred during dose escalation and resolved over time.¹

Labeling includes a Boxed Warning for thyroid C-cell tumors and is contraindicated in patients with a personal or family history of medullary thyroid carcinoma, with multiple endocrine neoplasia syndrome type 2, and with a known serious hypersensitivity to tirzepatide.¹

According to Lilly the anticipated list price for tirzepatide for weight management is $1059.87—“approximately 20% lower than semaglutide 2.4 mg injection for weight loss,” according to a press release. The company will be offering a commercial savings card program to help eligible individuals access the therapy.¹

References

1. FDA approves new medication for chronic weight management. News release. FDA. November 8, 2023. Accessed November 8, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management
2. FDA approves Lilly’s Zepbound (tirzepatide) for chronic weight management, a powerful new option for the treatment of obesity or overweight with weight-related medical problems. News release. Eli Lilly. November 8, 2023. Accessed November 8, 2023. https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-zepboundtm-tirzepatide-chronic-weight