Eli Lilly has said its weight-loss drug Zepbound was associated with greater weight reduction than higher-dose Wegovy HD in a new indirect comparison of clinical-trial data.

 

The analysis found that people taking Zepbound (tirzepatide) 15 mg lost an average of 4.5% more body weight than those taking Wegovy HD (semaglutide 7.2 mg) after 72 weeks under the study’s treatment-regimen analysis. Zepbound 10 mg was associated with 3.2% greater weight loss.

 

"For people living with obesity, the choice of treatment matters, and clinicians increasingly want evidence on how the available options compare," said John Wilding, 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."

 

The analysis was adjusted for gender, age, baseline weight and baseline A1C. Lilly said the treatment-regimen analysis showed greater weight reduction with both Zepbound doses at 72 weeks.

 

However, the results differed under the study's efficacy estimand, which looks at efficacy before treatment discontinuation. Under that analysis, Zepbound 15 mg was associated with 1.8% greater mean weight reduction and Zepbound 10 mg with 0.7% greater reduction than Wegovy HD — differences that did not reach statistical significance.

 

The analysis also found that people taking Zepbound 15 mg had higher odds of achieving at least a 20% reduction in body weight. The odds ratio was 4.15 under the efficacy estimand and 3.54 under the treatment-regimen estimand.

 

For Zepbound 10 mg, the analysis showed more than twice the odds of achieving at least 20% weight loss, although those differences were not statistically significant.

 

"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, 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."

 

The new analysis is not a head-to-head clinical trial of Zepbound 15 mg versus Wegovy HD. Instead, it uses statistical methods to compare results from separate trials, meaning the findings should be interpreted in that context.

 

The companies' drugs have previously been compared directly in Lilly's 72-week SURMOUNT-5 trial. In that study, which enrolled 751 adults with obesity or overweight and certain weight-related conditions but without diabetes, participants receiving Zepbound achieved an average weight reduction of 20.2%, compared with 13.7% among those receiving Wegovy, using the treatment-regimen analysis.

 

That represented a 47% greater relative weight loss, according to Lilly. Participants taking Zepbound lost an average of 50.3 pounds (22.8 kg), compared with 33.1 pounds (15.0 kg) for those taking Wegovy.

 

The new analysis reported comparable rates of treatment discontinuation due to adverse events between Zepbound and Wegovy HD across the two statistical approaches.

 

Zepbound is a prescription medicine containing tirzepatide, a dual GIP and GLP-1 receptor agonist. Lilly says it is approved for adults with obesity, or some adults who are overweight and have weight-related medical problems, to help lose weight and keep it off. It is also FDA-approved for adults with moderate-to-severe obstructive sleep apnea and obesity.