The obesity treatment drug 'Zepbound' (ingredient name tirzepatide) from the U.S. pharmaceutical company Eli Lilly has been found to have a greater weight loss effect than the 'Wegovy' (semaglutide) from Denmark's Novo Nordisk.
Researchers from Weill Cornell Medicine noted that "patients administered Zepbound experienced an average weight reduction of 20.2%, while those given Wegovy showed a reduction of 13.7%,” publishing their findings in the international journal 'New England Journal of Medicine' on Nov. 11 (local time). This study involved Texas A&M University, the University of California, NewYork-Presbyterian Hospital, Trinity College Dublin, and Lilly.
The researchers evaluated the weight loss efficacy and safety of Zepbound and Wegovy by administering maximum doses to 751 patients who were obese but did not have type 2 diabetes, comparing the results at the 72-week mark.
At the 72-week mark, the average weight loss rate for the Zepbound group (10 mg·15 mg) was 20.2%, showing a 47% improvement over the 13.7% observed in the Wegovy group (1.7 mg·2.4 mg). Patients receiving Zepbound lost an average of 22.8 kg, while those in the Wegovy group lost 15.0 kg.
The group administered Zepbound showed a higher likelihood of reaching their weight loss goals compared to those given Wegovy. The achievement rate for over 15% weight loss in the Zepbound group was 64.6%, whereas it was 40.1% in the Wegovy group. A comparison of waist circumference measurements revealed that Zepbound reduced it by an additional 5.4 cm.
The fact that Zepbound has a higher weight loss effect than Wegovy has been confirmed in previous studies. In December last year, Lilly noted that in a comparison involving patients with obesity in the U.S. and Puerto Rico, Zepbound had a weight loss effect 47% greater than that of Wegovy. In that study, the Zepbound group saw an average weight reduction of 20.2% after 72 weeks, while the Wegovy group saw a reduction of 13.7% over the same period.
Both Zepbound and Wegovy were originally developed as diabetes treatments, but their weight loss effects were recognized as side effects, leading to their new formulation as once-a-week obesity treatment injections. Both are glucagon-like peptide (GLP)-1 analogs that contribute to weight loss by engaging in insulin production and appetite regulation.
However, there is a distinction. While Wegovy only activates GLP-1 hormone receptors, Zepbound mimics both GLP-1 and gastric inhibitory peptide (GIP) simultaneously. GIP helps to reduce hunger as well as lower blood sugar levels, break down fat cells, and alleviate nausea.
Professor Louis Aronne from Weill Cornell Medicine, who led the study, said, "The direct comparison results between Zepbound and Wegovy demonstrate the improved weight loss effect of Zepbound" and indicated that "such results may be influenced by the differentiation in the mechanisms of weight loss action."
Currently, Dr. Aronne's research team is conducting clinical trials to determine whether GLP-1 obesity medications reduce the risk of cardiovascular diseases, including heart attacks and strokes. They have also begun clinical trials on next-generation obesity drugs, including Lilly's retatrutide, which mimics three hormones known as 'triple G' (GLP-1·GIP·glucagon).
References
New England Journal of Medicine (2025), DOI: https://doi.org/10.1056/NEJMoa2416394