The news release from Eli Lilly and Company, titled “Lilly’s Zepbound® (tirzepatide) superior to Wegovy® (semaglutide) in head-to-head trial, highlights the critical comparison of Zepbound vs Wegovy in treating obesity. Zepbound has shown superior efficacy, making it a compelling option for managing weight in adults.

The SURMOUNT-5 trial involved adults living with obesity or overweight with at least one weight-related medical condition but without diabetes. Zepbound outperformed Wegovy on both the primary endpoint and five key secondary endpoints at 72 weeks. The trial demonstrated that Zepbound was superior to Wegovy in terms of weight loss. Participants using Zepbound achieved an average weight loss of 20.2%, compared to 13.7% for those taking Wegovy. In terms of absolute weight loss, those on Zepbound lost 50.3 lbs (22.8 kg), while participants on Wegovy lost 33.1 lbs (15.0 kg). A key secondary endpoint showed that 31.6% of people taking Zepbound achieved at least 25% body weight loss, compared to just 16.1% of those taking Wegovy.

Mechanism of Action – Zepbound vs Wegovy

Tirzepatide, the active ingredient in Zepbound, is a dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist. In contrast, semaglutide is a mono GLP-1 receptor agonist.

Safety Profile

The overall safety profile of Zepbound in the SURMOUNT-5 trial was similar to previous studies. The most commonly reported adverse events were gastrointestinal-related and generally mild to moderate in severity.

Regulatory and Market Status

Tirzepatide is commercialized as Zepbound for adults with obesity or overweight and weight-related medical problems in some global markets outside the U.S. It received U.S. FDA approval on November 8, 2023, for this indication and is also marketed as Mounjaro for adults with type 2 diabetes.

Ongoing and Future Zepbound Studies

Ongoing studies of tirzepatide focus on its effects in four disease areas. These areas are chronic kidney disease (CKD), morbidity/mortality in obesity (MMO), moderate-to-severe obstructive sleep apnea (OSA), and heart failure with preserved ejection fraction (HFpEF). The data reinforces the efficacy and safety of Zepbound vs Wegovy in managing obesity. Zepbound is a significant treatment option for adults with obesity or those who are overweight and facing related medical challenges.