2023 in Review: Tirzepatide for Obesity

Educational Objectives

Summary

2023 in Review: Tirzepatide, Another Drug for Treating Patients with Obesity

On November 8, 2023, the U.S. FDA approved tirzepatide (https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management), the first agonist of both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, for treating obesity in patients without diabetes. For this indication, tirzepatide will be branded as Zepbound. Tirzepatide previously has been approved for treating patients with type 2 diabetes, under the brand name Mounjaro.

Approval of tirzepatide for obesity was based on two large, randomized trials in the New England Journal of Medicine and The Lancet. In a trial published in 2022 (https://doi.org/10.1056/NEJMoa2206038), 2500 adults with obesity but without diabetes were randomized to subcutaneous tirzepatide (5, 10, or 15 mg weekly) or placebo. In the second trial, published in 2023 (https://doi.org/10.1016/S0140-6736(23)01200-X), 900 adults with body-mass index (BMI) ≥27 kg/m² and diabetes (glycosylated hemoglobin, 7%–10%) were randomized to subcutaneous tirzepatide (10 or 15 mg weekly) or placebo. Patients in both trials received lifestyle advice and were followed for 72 weeks, including a 20-week dose escalation period.

On average, patients without diabetes who were taking tirzepatide lost 15% to 22% of their baseline bodyweight, and those with diabetes who were taking tirzepatide lost 13% to 15% of their baseline bodyweight. Patients in both trials who received placebo lost 3% of their baseline bodyweight. Among patients without diabetes in the two higher-dose tirzepatide groups, more than half lost at least 20% of their baseline body weight, compared with only 3% of patients in the placebo group.

Zepbound is indicated for patients with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related complication. Zepbound is administered at a starting dose of 2.5 mg weekly and increased in 2.5-mg increments every 4 weeks to a maximum of 15 mg weekly — a dosing schedule identical to that of Mounjaro. The most common dose-limiting side effects are gastrointestinal.

Tirzepatide is the second weekly GLP-1 agonist approved for treating patients with obesity, joining semaglutide (trade name: Wegovy), which has been in high demand since its approval for this indication in 2021. Tirzepatide led to somewhat more weight loss than semaglutide in comparable trials, perhaps because tirzepatide binds to GIP as well as GLP-1 receptors. Notably, both agents led to greater weight loss in patients without diabetes than those with diabetes. Access to both medications will be limited by cost: List prices, as recently stated by the manufacturers themselves, are US$1349 monthly for Wegovy and $1060 monthly for Zepbound. For insured patients, coverage and copayments obviously will vary depending on the insurance plan. Perhaps competition will lead to lower prices over time.

Bruce Soloway, MD

Readings

Disclosures

Dr. Allan Brett and Dr. Molly Brett reported having no financial conflicts of interest.

Acknowledgements

CME/CE INFO

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