Zepbound Surpasses Wegovy in Head-to-Head Weight Loss Trial

A recent clinical trial has demonstrated that Eli Lilly's innovative obesity medication, Zepbound (tirzepatide), leads to significantly greater weight loss compared to Novo Nordisk's Wegovy (semaglutide). The study, published in the New England Journal of Medicine, involved 751 overweight and obese participants across the United States who had additional weight-related health issues but did not have diabetes. Participants received weekly injections of either Zepbound or Wegovy over a period of 72 weeks.

Results revealed that those treated with Zepbound lost an average of nearly 50 pounds, equating to about 20% of their body weight. In contrast, Wegovy users lost approximately 33 pounds or about 14% of their initial weight. The reduction in waist circumference was also notable, with Zepbound users experiencing an average decrease of 7 inches, compared to approximately 5 inches in the Wegovy group.

Both medications work by mimicking hormones that regulate appetite and promote feelings of fullness, but Zepbound uniquely targets two hormones—GLP-1 and GIP—whereas Wegovy targets only GLP-1. This dual targeting is believed to enhance weight loss efficacy, as noted by the study's lead researcher, Dr. Louis Aronne of Weill Cornell Medicine.

The study also found that around 32% of Zepbound users achieved a weight loss of at least 25%, double the rate observed in Wegovy users. Additionally, both drugs contributed to health improvements such as lower blood pressure, blood sugar, and lipid levels. Common side effects included mild to moderate gastrointestinal issues like nausea and diarrhea, with a small percentage of participants discontinuing due to side effects.

The popularity of these medications is reflected in their substantial sales, with Zepbound earning $4.9 billion globally in 2024 and Wegovy nearly $8.8 billion. Both drugs are now more accessible after being removed from the FDA's shortage list, and programs are underway to reduce their monthly cost to $500 or less. However, recent decisions by CVS Health have favored Wegovy as the preferred drug on its formulary from July 1, 2025, potentially influencing prescriptions.

Experts emphasize the importance of utilizing multiple treatment options to meet the growing demand for effective obesity management, noting that Wegovy also offers additional benefits such as reducing cardiovascular risk.

Source: https://medicalxpress.com/news/2025-05-zepbound-outperforms-wegovy-weight-loss.html