Tirzepatide Outperforms Semaglutide in Weight Loss Trial

Tirzepatide and semaglutide, both medications for obesity treatment, demonstrate similar safety and efficacy but tirzepatide resulted in greater levels of weight loss among patients compared with semaglutide. | Image Credit: ricka_kinamoto - stock.adobe.com

Participants demonstrated a 47% greater relative weight loss on tirzepatide (Zepbound) compared with semaglutide (Wegovy), according to a press release from Eli Lilly and Company, maker of tirzepatide.1

The SURMOUNT-5 (NCT05822830) phase 3b open-label, randomized clinical trial included adults who did not have diabetes but had obesity or were overweight in conjunction with hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease.

“Given the increased interest around obesity medications, we conducted this study to help health care providers and patients make informed decisions about treatment choice,” Leonard C. Glass, MD, FACE, senior vice president of global medical affairs at Lilly Cardiometabolic Health, said in a statement.

There were 751 patients across the US and Puerto Rico randomized to receive either the maximum tolerated dose of 10 mg or 15 mg of tirzepatide or 1.7 mg or 2.4 mg of semaglutide. By week 72, tirzepatide demonstrated more weight loss compared with semaglutide, meeting the primary end point. Additionally, the secondary end point was achieved when 31.6% of patients taking tirzepatide achieved at least 25% body weight loss compared with 16.1% of the patients taking semaglutide.

The FDA approved semaglutide for weight loss in June 2021, making the glucagon-like peptide-1 (GLP-1) receptor agonist the first approval since 2014 targeted toward obesity and weight management.2 Semaglutide is offered as a 2.4-mg once-daily injection under the name Wegovy; the 1-mg injection is sold as Ozempic to treat type 2 diabetes.

Less than a year after semaglutide’s weight loss indication, tirzepatide was approved by the FDA as Mounjaro for adults with type 2 diabetes to improve glycemic control. About a year ago, the FDA also approved tirzepatide under the brand name Zepbound as another diabetes drug to treat chronic weight management combined with weight-related medical conditions.3 Tirzepatide is a glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor administered by injection once a week.

Common adverse events of tirzepatide include nausea, diarrhea, vomiting, constipation, abdominal pain, indigestion, injection site reactions, fatigue, allergic reactions, belching, hair loss, and heartburn.1 Semaglutide has similar adverse events but also includes headache, vitreous hemorrhage in patients with diabetic retinopathy, anxiety, dizziness, and erythema at the injection site.4

Prices for tirzepatide vary based on the type of insurance the patient has. Without insurance, a 28-day supply of tirzepatide is listed for $1060, or $13,800 a year.5 Single-use pens were introduced recently for about half of the list price with a 4-week supply costing $399 for 2.5-mg doses and $549 for 5-mg doses.

Patients who are insured by Medicaid have different list prices based on the state, and Medicare Part D plans do not cover weight-loss medications. The Biden administration has proposed revisions to Medicare and Medicaid regulations to cover obesity treatments.6 These changes in policies would take effect among existing programs in 2026, allowing greater accessibility to patients who do not have this form of insurance coverage.

The new proposal suggests plan coverage across antiobesity medications while addressing long-term weight management to prevent further complications, comorbidities, and conditions. CMS estimates 3.4 million patients who use Medicare and 4 million who use Medicaid could qualify for obesity medications if the Trump administration supports the policy proposal.

Last year, the American Medical Association (AMA) called on insurance companies to broaden coverage for evidence-based treatments of obesity without exclusions.7 The AMA acknowledges obesity as a disease that can lead to severe health complications, especially when left untreated. It emphasized the urgency of resolving these issues by reducing the costs of medications, which create a substantial barrier in access for patients who do not have health plan coverage for obesity drugs.

“Zepbound [tirzepatide] is in a class of its own as the only FDA-approved dual GIP and GLP-1 receptor agonist obesity medication, and it’s changing how millions of people manage this chronic disease,” stated Glass.

References

1. Lilly’s Zepbound (tirzepatide) superior to Wegovy (semaglutide) in head-to-head trial showing an average weight loss of 20.2% vs 13.7%. News release. Lilly; December 4, 2024. Accessed December 4, 2024. https://investor.lilly.com/news-releases/news-release-details/lillys-zepboundr-tirzepatide-superior-wegovyr-semaglutide-head
2. Inserro A. FDA clears semaglutide for weight loss when used with diet, exercise. AJMC®. June 4, 2021. Accessed December 4, 2024. https://www.ajmc.com/view/fda-clears-semaglutide-for-weight-loss-when-used-with-diet-exercise
3. Joszt L. FDA approves diabetes drug tirzepatide for chronic weight management. AJMC. November 8, 2023. Accessed December 4, 2024. https://www.ajmc.com/view/fda-approves-diabetes-drug-tirzepatide-for-chronic-weight-management
4. Kommu S, Whitfield P. Semaglutide. In: StatPearls. February 11, 2024. Accessed December 4, 2024. https://www.ncbi.nlm.nih.gov/books/NBK603723/
5. Holmes TE. Zepbound (Tirzepatide) for weight loss: learn about the cost. GoodRx. September 20, 2024. Accessed December 4, 2024. https://www.goodrx.com/zepbound/weight-loss-tirzepatide-cost
6. Munz K. New proposal aims to expand Medicaid and Medicare coverage for obesity drugs. AJMC. November 26, 2024. Accessed December 5, 2024. https://www.ajmc.com/view/new-proposal-aims-to-expand-medicaid-and-medicare-coverage-for-obesity-drugs
7. AMA urges insurance companies parity for emerging obesity treatment options. Press release. AMA; November 14, 2023. Accessed December 5, 2024. https://www.ama-assn.org/press-center/press-releases/ama-urges-insurance-coverage-parity-emerging-obesity-treatment-options