More patients on Eli Lilly’s tirzepatide lost over 5% of their lean mass versus those on Novo Nordisk’s semaglutide, according to a study that has yet to be peer reviewed.
Novo Nordisk’s GLP-1 drug semaglutide appears to carry better body composition effects than Eli Lilly’s tirzepatide, giving the Danish pharma a much-needed advantage over its chief competitor.
These findings come from an observational study posted Monday on the preprint server medRxiv. Preprints present “new medical research that has yet to be evaluated and so should not be used to guide clinical practice,” the site itself cautions.
In the study, researchers looked at the records of nearly 8,000 patients with available body composition assessments before and after starting GLP-1 treatment. They then categorized participants based on their patterns of weight loss.
The first cohort, composed of patients who lost more than 20% of their total body weight and over 5% of their lean body mass, was called a “depletive GLP-1 metabotype.” The second group, dubbed “prime GLP-1 metabotype,” included those who lost more than 10% of their total weight but less than 5% of their lean mass.
During the first year of treatment, 10.3% of patients on tirzepatide fell under the depletive GLP-1 metabotype, compared with only 6.7% of patients taking semaglutide. The difference was statistically significant in favor of Novo’s drug. Meanwhile, 12.3% of patients on semaglutide fit the prime GLP-1 metabotype, versus 11.8% of those on tirzepatide. The difference in this second comparison was not significant.
The preprint also found that a higher GLP-1 dose and longer exposure correlated with greater decline in lean body mass across both semaglutide and tirzepatide groups.
“Greater weight-loss efficacy did not necessarily translate into more favorable body-composition outcomes,” the researchers wrote.
The findings are in line with previous results showing greater weight loss for patients on tirzepatide than on semaglutide. If the findings of greater lean mass preservation with Novo’s drug are borne out in controlled and head-to-head studies, they could serve as a key advantage over its primary competitor that could help the Danish company claw back some market share. Despite being years ahead to the market, Novo’s semaglutide franchise has fallen behind Lilly’ tirzepatide products, something that analysts have chalked up to Lilly’s stronger commercial execution.
The rivalry between Novo and Lilly has recently been renewed after the FDA signed off on the Indiana pharma’s weight loss pill Foundayo, setting it up for a direct face-off against Novo’s oral Wegovy.
Ahead of its launch, however, Foundayo already faced complications, with the FDA in its approval letter noting “unexpected” and “serious” cardiovascular and liver safety risks. The drug may already have assuaged some of these concerns, however, with Phase 3 data shared Thursday showing marked reductions in major adverse cardiovascular events with no drug-induced liver injuries compared to insulin.
