In addition to eliciting greater weight loss than Novo Nordisk’s Wegovy, Eli Lilly’s Zepbound does not come at the expense of safety, according to newly released comprehensive tolerability data—findings that Leerink analysts say confirm the GLP-1 drug’s edge in the closely watched market race.
Eli Lilly maintained the upper hand in the closely watched obesity face-off, announcing on Sunday full data from a trial showing that patients on Zepbound lost more weight than those on Novo Nordisk’s Wegovy while matching its safety.
Pointing to what they called Zepbound’s “comparable tolerability” to Wegovy, these latest data “confirm tirzepatide’s superior benefit-risk ratio,” analysts at Leerink Partners wrote in a note to investors on Monday.
Sunday’s readout comes from the Phase IIIb SURMOUNT-5 study, an open-label trial that pit Zepbound directly against Wegovy, enrolling more than 750 overweight and obese patients with at least one weight-related comorbidity but who didn’t have diabetes.
At 72 weeks, patients on Zepbound lost 20.2% of their body weight on average, as compared with 13.7% in those on Wegovy, a 47% relative weight loss advantage for Zepbound over Wegovy. Zepbound was likewise superior to Wegovy in terms of key secondary endpoints, such as the percentage of treated patients losing at least a quarter of their weight.
Lilly shared similar data in December 2024, when it released a topline readout from SURMOUNT-5. At the time, however, Lilly did not present tolerability data—the pharma only revealed that Zepbound’s adverse event profile “was similar” to what had previously been reported in the SURMOUNT program.
Compete data from SURMOUNT-5, published Sunday in the New England Journal of Medicine, provide a comprehensive safety comparison between the two drugs—and found that despite hitting greater weight-loss, Zepbound does not carry a higher burden of toxicities. Side effects were nausea, constipation, vomiting and diarrhea.
Serious adverse events occurred in 4.8% of Zepbound-treated patients versus 3.5% in those on Wegovy. Six patients in each treatment group dropped out of the study due to side effects. SURMOUNT-5 did not detect any treatment-related deaths.
Lilly will transition patients who complete SURMOUNT-5 into the Phase IIIb extension ATTAIN-MAINTAIN study, which will test the efficacy of switching patients to the oral obesity drug orforglipron, Lilly’s next generation GLP-1 drug, to help them maintain their weight-loss. The study’s primary completion date is in January 2026.
Last month, Lilly released Phase III data for orforglipron, touting a 7.9% reduction in body weight over 40 weeks of follow-up, as opposed to 1.6% in placebo. Analysts lauded these results at the time, with BMO Capital Markets analysts calling it “injectable like.”
Sunday’s SURMOUNT-5 readout is just the latest development in what has been a tight competition between Lilly and Novo as they jockey for leadership in the lucrative obesity space. Earlier this month, CVS Caremark, one of the biggest pharmacy benefit managers in the U.S., chose Wegovy over Zepbound as its “preferred GLP-1 medicine,” effective July 1.
While this move could give Wegovy a boost in the market, Lilly appears unfazed. During the company’s Q1 earnings call, CEO David Ricks told investors that pharma was “not surprised” by CVS’ choice and instead remains confident in its commercial execution. “If we look at what’s happening in the market, we’re pretty deep into a replacement cycle, particularly on obesity,” Ricks said.
