The FDA approved tirzepatide (Zepbound), the latest injectable for chronic weight management in adults, the agency announced on Wednesday.
The combination glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist is indicated for adults with obesity or overweight with at least one weight-related condition, alongside a reduced-calorie diet and increased physical activity.
Eli Lilly’s first-in-class compound was first approved for type 2 diabetes under the trade name Mounjaro last year and shot to popularity for its off-label use for weight loss. The agent works by activating receptors of the GLP-1 and GIP hormones secreted from the intestine to curb appetite and food intake.
The extremely effective drug will rival GLP-1 receptor agonist semaglutide 2.4 mg (Wegovy), which was approved in 2021. The FDA noted that the safety and effectiveness of tirzepatide co-administered with other medications for weight management have not been established.
“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, in the statement. “In light of increasing rates of both obesity and overweight in the United States, today’s approval addresses an unmet medical need.”
Data from the SURMOUNT-1 and -2 trials supported the approval. In SURMOUNT-1, 15 mg of the once-weekly injectable led to an average 18% loss of body weight compared with placebo in people with overweight (body mass index [BMI] ≥27) or obesity (BMI ≥30) without diabetes. Subsequently, the SURMOUNT-2 trial reported that people with overweight or obesity and type 2 diabetes taking the same dose lost on average 12% of their body weight versus those randomized to placebo.
According to the drug’s label, the recommended starting dosage is 2.5 mg injected subcutaneously once weekly and can be increased to 5 mg once weekly after 4 weeks. The dosage can be uptitrated in 2.5-mg increments after at least 4 weeks on the current dose. The recommended maintenance dosages are 5 mg, 10 mg, or 15 mg once weekly.
As expected with an agent containing GLP-1, gastrointestinal-related side effects were commonly reported during the clinical trials and occurred more frequently during the uptitration phase. The most common side effects that occurred in ≥5% of patients were nausea, diarrhea, vomiting, constipation, abdominal discomfort and pain, injection site reactions, fatigue, hypersensitivity reactions (typically fever and rash), burping, hair loss, and gastroesophageal reflux disease.
Tirzepatide is contraindicated in people with a personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2.
The label also includes warnings on pancreatitis, gallbladder problems, hypoglycemia, acute kidney injury, diabetic retinopathy in patients with type 2 diabetes, and suicidal behavior or thinking. Patients with symptoms of pancreatitis or gallstones should have a discussion with their clinician prior to initiating treatment. Healthcare providers should monitor patients with kidney disease, diabetic retinopathy, and depression or suicidal behaviors or thoughts.
Clinicians should also speak to their patients on insulin or a medication that causes insulin secretion about potentially lowering the dose of these other medicines to reduce the risk of hypoglycemia.
According to Eli Lilly, tirzepatide is expected to be available in the U.S. by the end of the year in six doses at a list price of $1,059.87, which is approximately 20% lower than semaglutide 2.4 mg.