Zepbound associated with more weight loss than Wegovy HD in a new indirect treatment comparison – Eli Lilly
Eli Lilly and Company 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 randomized 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.
“For people living with obesity, the choice of treatment matters, and clinicians increasingly want evidence on how the available options compare,” said John Wilding, DM, professor of medicine at the University of Liverpool. “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% more of their body weight (95.0% CrI: -6.3, -2.8) on average, and those taking 10 mg lost 3.2% more of their body weight (95.0% CrI: -5.0, -1.4). Using the efficacy estimand, Zepbound 15 mg and 10 mg were associated with 1.8% (95.0% CrI: -3.8, 0.1) and 0.7% (95.0% CrI: -2.6, 1.3) greater mean weight reduction than Wegovy HD, respectively, though these differences did not reach statistical significance.
“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,” said Thomas Seck, M.D., senior vice president of product development, Lilly Cardiometabolic Health. “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 four times more likely to achieve 20% or greater body weight reduction compared with Wegovy HD using the efficacy estimand (odds ratio 4.15; 95.0% CrI: 1.02, 15.64), and more than three times more likely using the treatment-regimen estimand (odds ratio 3.54; 95.0% CrI: 1.05, 11.05). While not statistically significant, participants taking Zepbound 10 mg had more than two times the odds of achieving at least 20% body-weight reduction compared with Wegovy HD using the efficacy (odds ratio 2.8; 95.0% CrI: 0.7, 10.8) and treatment-regimen estimands (odds ratio 2.46; 95.0% 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.
About SURMOUNT-1 and the SURMOUNT clinical trial program
SURMOUNT-1 (NCT04184622) is a multi-center, randomized, double-blind, parallel, placebo-controlled trial comparing the efficacy and safety of tirzepatide 5 mg, 10 mg and 15 mg to placebo as an adjunct to a reduced-calorie diet and increased physical activity in adults without type 2 diabetes who have obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease. The trial randomized 2,539 participants across the U.S., Argentina, Brazil, China, India, Japan, Mexico, Russia and Taiwan in a 1:1:1:1 ratio to receive either tirzepatide 5 mg, 10 mg or 15 mg or placebo. The co-primary objectives of the study were to demonstrate that tirzepatide 10 mg and/or 15 mg is superior in percentage of body weight reductions from baseline and percentage of participants achieving ≥5% body weight reduction at 72 weeks compared to placebo. The SURMOUNT phase 3 global clinical development program for tirzepatide in chronic weight management began in late 2019 and has enrolled more than 5,000 people with obesity or overweight across six registration studies, four of which are global studies.
About SURMOUNT-5
SURMOUNT-5 (NCT05822830) was a 72-week, multi-center, randomized, open-label, Phase 3b trial evaluating the efficacy and safety of Zepbound (tirzepatide) compared with Wegovy (semaglutide) in adults with obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea (OSA) or cardiovascular disease, who did not have diabetes. Participants in both treatment groups received counseling on a reduced-calorie diet and increased physical activity. The trial randomized 751 participants across the U.S. and Puerto Rico in a 1:1 ratio to receive maximum tolerated dose of Zepbound (10 mg or 15 mg) or Wegovy (1.7 mg or 2.4 mg). With tirzepatide, 89.3% received at least one dose of the 15 mg dose and with semaglutide 92.8% received at least one dose of the 2.4 mg dose. The primary objective of the study was to demonstrate Zepbound’s superiority in percent change from baseline in body weight at 72 weeks compared to Wegovy. For the primary endpoint, participants treated with Zepbound achieved an average weight reduction of 20.2% compared to 13.7% with Wegovy at 72 weeks using the treatment-regimen estimand, a 47% greater relative weight loss. Participants using Zepbound lost an average of 50.3 lbs (22.8 kg) and participants on Wegovy lost an average of 33.1 lbs (15.0 kg).
