The drug, Zepbound, will be available in the United States by the end of 2023.
The FDA has approved tirzepatide injection (Zepbound) for chronic weight management in adults with overweight or obesity and at least 1 weight-related condition, for use as an adjunct to a reduced calorie diet and an increase in physical activity, according to an agency press release. The approval comes after the FDA granted tirzepatide injection Priority Review and Fast Track designations for this indication.1,2
Tirzepatide injection is the first and only obesity treatment that activates hormone receptors for both glucose-dependent insulinotropic polypeptides (GIP) and glucagon-like peptide 1 (GLP-1).
“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.”
Per the FDA, approximately 70% of American adults have obesity or overweight, defined as a body mass index of 30 kg/m2 and 27 kg/m2, respectively. Many of these adults are also living with a weight-related condition, such as hypertension, type 2 diabetes, or dyslipidemia. Losing just 5% to 10% of body weight is associated with a reduced risk of cardiovascular disease in this patient population.
Zepbound works by activating receptors of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) to reduce both appetite and food intake. It is administered via injection under the skin once per week; the dosage must be increased over a period of 4 to 20 weeks to achieve the target dose of either 5 mg, 10 mg, or 15 mg once weekly.
Effectiveness for chronic weight management—both weight reduction and maintenance—in combination with a reduced-calorie diet and increased physical activity was established in 2 phase 3, randomized, double-blind, placebo-controlled clinical trials, SURMOUNT-1 (NCT04184622) and SURMOUNT-2 (NCT04657003). 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.
Investigators in the SURMOUNT-1 trial compared 2539 adults with obesity or excess weight and weight-related medical problems not including diabetes vs a placebo group. 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. When analyzing uncontrolled data, investigators found that 1 in 3 patients in the treatment group taking the highest dose lost more than 58 lbs, or 25% of their body weight, compared with 1.5% of body weight lost in the placebo group. The average starting weight of participants was 231 lbs and average body mass index was 38 kg/m2; weight loss at all 3 dose levels was statistically significant.
In SURMOUNT-2, which included adults with type 2 diabetes, average participant body weight was 222 lbs and average body mass index was 36 kg/m2. Participants randomly assigned to receive the 15 mg dose lost an average of 12% of their body weight vs 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.2 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.”
Potential adverse effects of tirzepatide injection include gastrointestinal adverse reactions. The most commonly reported events, noted in ≥5% of trial participants, included nausea, diarrhea, vomiting, constipation, abdominal pain, dyspepsia, injection site reactions, fatigue, hypersensitivity reactions, eructation, hair loss, and gastroesophageal reflux disease. 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.
Manufacturer Eli Lilly anticipates that Zepbound will be available in the United States by the end of 2023 at 6 dose strengths: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg. Anticipated list price 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 individuals who may benefit from the therapy access it.
Tirzepatide is already approved under the brand name Mounjaro, for use—along with diet and exercise—to improve HbA1c in adults with type 2 diabetes.