Novo Nordisk's GLP-1 drug semaglutide may offer better preservation of lean body mass compared to Eli Lilly's tirzepatide, according to an observational study posted on the preprint server medRxiv on April 17. The study analyzed records from nearly 8,000 patients who had undergone body composition assessments before and after starting GLP-1 treatment.
The topic is significant as both drugs are major players in the growing weight-loss market, with competition intensifying between Novo Nordisk and Eli Lilly. Body composition effects are important for patient health beyond simple weight loss.
Researchers categorized patients into two groups: a “depletive GLP-1 metabotype,” which included those losing more than 20% of total body weight and over 5% of lean mass, and a “prime GLP-1 metabotype,” defined by more than 10% total weight loss but less than 5% lean mass loss. During the first year of treatment, a higher percentage of tirzepatide users (10.3%) fell into the depletive group compared to semaglutide users (6.7%), a statistically significant difference favoring Novo Nordisk’s drug. For the prime metabotype group, results were similar between both drugs.
The preprint also reported that higher doses and longer exposure to either medication led to greater declines in lean body mass overall. The researchers wrote: “Greater weight-loss efficacy did not necessarily translate into more favorable body-composition outcomes.”
Analysts from Leerink Partners commented that they were underwhelmed by these findings, writing that the "retrospective study fails to state the obvious"—that changes in muscle mass reflect overall changes in body weight.
Despite being earlier to market with its semaglutide franchise, Novo Nordisk has recently fallen behind Eli Lilly’s tirzepatide products due largely to what analysts describe as stronger commercial execution by Lilly. However, if further studies confirm that semaglutide preserves lean muscle better than tirzepatide, this could become an advantage for Novo Nordisk as competition continues.
