In a new clinical study, Tirzepatide, a new dual agonist, comes out on top addressing two hormone pathways. It far exceeds Semaglutide, a GLP-1 agonist, in its ability to induce weight loss in individuals fighting obesity. The study was first presented at the European Congress on Obesity 2025 in Spain and published in The New England Journal of Medicine. It was huge, with 751 participants, who had fought the battle of the bulge for an average of 16 years. All had tried unsuccessfully to lose weight with diet alone first.
Participants taking Tirzepatide lost an average of 20% of their body weight. People on Semaglutide had a weight loss of about 14%. Participants on Tirzepatide lost 35% of their weight on average. The Bucner participants experienced an unprecedented cut in waist size—with an average 7-inch decrease—compared to an average 5-inch reduction for those on Semaglutide.
Features of the study’s design were especially remarkable in that it was the first-ever head-to-head trial comparing these two medications directly. Tirzepatide was given to half of the participants, and Semaglutide to the other half. This design allowed researchers to easily compare the two treatment choices side-by-side.
Importantly, 32% of patients treated with Tirzepatide reached a minimum weight loss of 25% or greater. In comparison, just 16% of Semaglutide users achieved that level of weight loss. These findings highlight the meaningfulness and impact that Tirzepatide treatment could provide for patients with severe and complex obesity.
Tirzepatide operates on two hormone pathways: GLP-1 and GIP. The combined effect of these two actions enhances weight loss and appetite suppression benefits to a major extent. Partially achieves this by boosting the hunger-suppressing effects of GLP-1 and targeting other mechanisms through GIP. Meanwhile, Semaglutide only gives the GLP-1 pathway a boost.
Those who work in the policy field understand what might be at stake with these findings. Dr. David Horner noted, “One is not in doubt that tirzepatide has a greater weight loss benefit from the data. We’re comparing a very good drug with a very good drug.” This sentiment illustrates the increasing recognition that new and varied mechanisms can improve obesity treatment success.
Dr. Louis J. Aronne emphasized the broader implications of weight loss on metabolic health. “In general, the more weight someone loses, then the better the metabolic parameters will be.” He equally noted that recent developments in new obesity medicines could potentially address former barriers. “We’ve learnt over the past 20 years or so that you can overcome the plateau effect with obesity drugs if you can add in drugs with mechanisms that are completely different.”
This is because the study’s participants had already tried a dozen different diets and weight-loss methods without much success. With this new research, it’s never been more possible to help those who have fought a long battle against obesity find a better solution.
Pharma companies vast sums are focusing on finding new breakthroughs for obesity. Today, nearly 150 drugs are in clinical trial to address this urgent epidemic. Findings from this study could lay the foundation for continued advancements in targeted, effective therapies.
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