Eli Lilly and Company has announced results from a new analysis showing that Zepbound (tirzepatide) 10 mg and 15 mg, a dual GIP and GLP-1 receptor agonist, delivered greater weight loss than Wegovy HD (semaglutide injection 7.2 mg) in adults with obesity.

The findings come from an indirect treatment comparison of Zepbound and Wegovy HD, drawing on data from the SURMOUNT-1 and STEP UP trials. These results, presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy, add to the growing body of evidence comparing Zepbound and Wegovy, including SURMOUNT-5, a randomised controlled phase 3b trial in which Zepbound 10 mg and 15 mg demonstrated superior weight loss compared with Wegovy 1.7 mg and 2.4 mg.

John Wilding, DM, Professor of Medicine, University of Liverpool, said, "For people living with obesity, the choice of treatment matters, and clinicians increasingly want evidence on how the available options compare. Tirzepatide 10 mg and 15 mg and semaglutide 1.7 mg and 2.4 mg were compared directly in SURMOUNT-5, where tirzepatide helped people with obesity lose more weight. In the absence of a head-to-head trial comparing tirzepatide 15 mg against semaglutide 7.2 mg, this indirect comparison offers useful evidence for physicians as they make treatment decisions."

In the indirect treatment comparison, which was covariate-adjusted for gender, age, baseline weight and baseline A1C, Zepbound 10 mg and 15 mg were associated with greater reductions in body weight than Wegovy HD at 72 weeks using the treatment-regimen estimand. Participants taking Zepbound 15 mg lost 4.5 percent more of their body weight (95.0 percent CrI: -6.3, -2.8) on average, and those taking 10 mg lost 3.2 percent more of their body weight (95.0 percent CrI: -5.0, -1.4). 

Using the efficacy estimand, Zepbound 15 mg and 10 mg were associated with 1.8 percent (95.0 percent CrI: -3.8, 0.1) and 0.7 percent (95.0 percent CrI: -2.6, 1.3) greater mean weight reduction than Wegovy HD, respectively, though these differences did not reach statistical significance.

Thomas Seck, MD, Senior Vice President—Product Development, Lilly Cardiometabolic Health, said, "People with obesity have more treatment options than ever before, and their healthcare providers deserve as much information as possible to help guide their decisions. In a head-to-head phase 3 clinical trial, Zepbound 10 mg and 15 mg delivered greater weight loss than Wegovy 1.7 mg and 2.4 mg, and a new indirect treatment comparison suggests the same doses of Zepbound may outperform Wegovy HD, as well. Together, these results offer physicians more information as they choose a treatment path."

In addition to achieving greater weight loss, participants taking Zepbound 15 mg were 4 times more likely to achieve 20 percent or greater body weight reduction compared with Wegovy HD using the efficacy estimand (odds ratio 4.15; 95.0 percent CrI: 1.02, 15.64), and over 3 times more likely using the treatment-regimen estimand (odds ratio 3.54; 95.0 percent CrI: 1.05, 11.05). While not statistically significant, participants taking Zepbound 10 mg had more than 2 times the odds of achieving at least 20 percent body-weight reduction compared with Wegovy HD using the efficacy (odds ratio 2.8; 95.0 percent CrI: 0.7, 10.8) and treatment-regimen estimands (odds ratio 2.46; 95.0 percent CrI: 0.7, 7.8).

Zepbound 10 mg and 15 mg showed comparable rates of treatment discontinuation due to adverse events versus Wegovy HD across both estimands.