Eli Lilly's Zepbound (tirzepatide) has demonstrated superior weight loss results compared to Novo Nordisk's Wegovy (semaglutide) in the first head-to-head clinical trial, potentially reshaping the obesity treatment landscape. The Phase 3b SURMOUNT-5 trial revealed that Zepbound led to an average weight loss of 20.2% of body weight, while Wegovy resulted in a 13.7% reduction over 72 weeks. This translates to a 47% greater relative weight loss for individuals treated with Zepbound.
The trial, which involved 751 adults across the U.S. and Puerto Rico, focused on participants who were either overweight or obese and had at least one comorbidity such as hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease, but excluded those with type 2 diabetes. Participants were randomized to receive either Zepbound or Wegovy, allowing for a direct comparison of the two drugs' efficacy and safety.
Key Findings from the SURMOUNT-5 Trial
The data indicated that patients on Zepbound experienced an average weight loss of 22.8 kg (50.3 pounds), compared to 15 kg (33.1 pounds) for those on Wegovy. Furthermore, a significant 31.6% of participants in the Zepbound group achieved at least 25% body weight loss, compared to only 16.1% in the Wegovy group. These results suggest a potentially greater impact on weight reduction for patients using Zepbound.
"Given the increased interest around obesity medications, we conducted this study to help health care providers and patients make informed decisions about treatment choice," said Leonard Glass, M.D., senior vice president of global medical affairs at Lilly Cardiometabolic Health. He further noted that the findings showed the superior weight loss of Zepbound, which helped patients achieve 47% more relative weight loss compared to Wegovy.
Mechanism of Action and Clinical Implications
Zepbound's active ingredient, tirzepatide, is a dual GIP and GLP-1 receptor agonist, while Wegovy's active ingredient, semaglutide, is a GLP-1 receptor agonist. This difference in mechanism may contribute to the observed differences in weight loss. Tirzepatide imitates both GLP-1 and GIP, which is believed to improve how the body breaks down sugar and fat, potentially leading to enhanced weight reduction.
Safety and Tolerability
Eli Lilly reported that the most commonly reported side effects for both Zepbound and Wegovy were gastrointestinal-related and generally mild to moderate in severity. These side effects are consistent with those observed in previous trials of both medications. However, a detailed comparison of the tolerability profiles of the two drugs was not disclosed in the initial press release, and analysts are awaiting further data on this aspect.
Market Impact and Future Directions
The results from the SURMOUNT-5 trial are expected to bolster Zepbound's market position in the competitive obesity treatment market. With the obesity market projected to reach $100 billion by 2030, both Eli Lilly and Novo Nordisk are vying for market share. The superior weight loss demonstrated by Zepbound could influence treatment decisions and potentially establish the drug as a new standard for obesity medications.
While Zepbound has shown promising results in weight loss, experts emphasize that treatment decisions should consider individual patient factors, including health outcomes beyond weight loss, cost, availability, and insurance coverage. Further research is also needed to explore the long-term effects of these medications and their impact on overall health outcomes.
