In Milan this week, Novo and Eli Lilly took the stage at the European Association for the Study of Diabetes 2026 meeting with dueling datasets on oral and injectable GLP-1s.
Among the mix of real-world evidence and indirect comparisons, Novo vouched for Ozempic’s edge at lowering the risk of serious cardiovascular events when compared to patients who switched to Lilly’s diabetes rival Mounjaro, harkening to a familiar perk of its semaglutide franchise.
And Lilly, for its part, parried with a new comparison—though not a strict head-to-head—touting its oral GLP-1 Foundayo’s superior weight loss and blood sugar level reduction versus Novo’s Wegovy pill, also in Type 2 diabetes, alongside another indirect assessment that tied its obesity injectable Zepbound to higher weight loss than Novo’s high-dose format of Wegovy.
The highly lucrative GLP-1 market shows no signs of letting up, with Novo and Lilly continuing to dominate as a wave of potential incretin challengers work through rival pipelines and the companies’ own. Novo has been fighting to regain market share from Lilly in the key U.S. market, although the launches of oral GLP-1s for weight loss earlier this year—starting with Novo’s Wegovy pill in January—have helped begin to tip the scales slightly back in the Danish drugmaker’s favor.
All the while, Novo and Lilly have continued to round out the evidence on their approved metabolic franchises, highlighting advantages not just across magnitude of weight loss, but also more holistic health benefits along the lines of semaglutide’s heart-helping potential.
On that front, Novo used the EASD annual meeting in Madrid Tuesday to trumpet a real-world analysis, which linked Type 2 diabetes patients on 1 mg of Ozempic who then moved up to the 2-mg format to a 6% lower risk of major adverse cardiovascular events (MACE) than those who instead switched to Lilly’s 15-mg Mounjaro.
The 6% risk reduction for MACE—which included all-cause death, heart attack and stroke—was statistically significant, Novo said in a Sept. 29 release.
While patients with Type 2 diabetes often need to switch treatments or adjust doses to get to glycemic control, “cardiovascular risk should also remain an important consideration,” Michael Radin, M.D., Novo’s executive medical director, said in a statement.
The analysis, dubbed Compete Switch CV, looked at 636,525 adults with Type 2 diabetes who began on 1-mg Ozempic. At the start of the retrospective, 67.2% of patients had stuck with that 1-mg dose, while another 29.2% escalated to Ozempic 2 mg and a final 3.6% had switched to Lilly’s Mounjaro within a year of their first prescription fill.
At 720 days, 57.4% of patients were on the 1-mg Ozempic dose, reflecting what Novo called “continued treatment intensification over time.” Over that span, 36.9% of patients had upped their Ozempic dose to 2 mg and 5.7% switched to Lilly’s medicine.
Also homing in on diabetes, Lilly rolled out new data at EASD on the 17.2-mg dose of its GLP-1 pill Foundayo (orforglipron), arguing via an indirect comparison that the drug was tied to “significantly greater weight loss and better blood sugar control” than Novo’s Wegovy pill at 25 mg.
Foundayo, which was approved in obesity in April, has not yet received FDA clearance in Type 2 diabetes, though Lilly has said it’s pursuing an expansion into that indication. Novo’s Wegovy pill is specifically cleared for chronic weight management, too, but the company also touts an oral diabetes counterpart in the Ozempic pill—a slight reformulation of the product Rybelsus, which Novo ushered into a soft retirement earlier this year.
Taking a closer look at Lilly’s indirect comparison between its Achieve-3 study and Novo’s Pioneer Plus trial, patients on Foundayo lost 1.5% more of their body weight on average compared to the Wegovy pill cohort, while Foundayo also reduced A1C by 0.3% more than oral semaglutide.
Analyses that relied on different methods produced “consistent results,” per Lilly. Foundayo 17.2 mg was linked to 1.5% to 2.4% greater weight loss and 0.3% to 0.6% greater A1C reduction versus oral semaglutide 25 mg on the whole.
The oral semaglutide dose Lilly used in its comparison corresponds to the Wegovy pill’s maintenance dose in obesity.
“Head-to-head trials ultimately provide the best comparison of two medicines, but when we don't yet have those data, then other approaches can provide informative data points,” Rachel Batterham, Ph.D., SVP of medical innovation and external engagement at Lilly cardiometabolic health, said in a statement.
“These results,” she added, “paired with simple administration free of fasting or water restrictions, are what make Foundayo a potentially foundational therapy for adults managing type 2 diabetes around the world.”
Aside from obesity and Type 2 diabetes, Lilly is also assessing the potential of its GLP-1 pill in obstructive sleep apnea, osteoarthritis knee pain, hypertension, peripheral artery disease and stress urinary incontinence.
Rounding out the datasets from Lilly was another indirect treatment comparison tying 10- and 15-mg Zepbound to greater weight loss than Wegovy HD (a 7.2-mg dose of the semaglutide injection) in adults with obesity.
Specifically, patients who took Zepbound lost 4.5% more of their body weight on average at 72 weeks than those on Wegovy HD, with the results working out to a 3.2% average weight-loss edge for Lilly on the 10-mg Zepbound dose.
Using the efficacy estimand, however—which represents efficacy prior to discontinuation of study drug—Zepbound 15- and 10-mg were tied to 1.8% and 0.7% greater mean weight reduction than Wegovy HD, respectively. Those results weren’t statistically significant, Lilly said.
The new data could help in doctors’ decision making since there isn’t currently a head-to-head trial comparing these specific doses of Zepbound and Wegovy, John Wilding, professor of medicine at the University of Liverpool, said in Lilly’s release.
“For people living with obesity, the choice of treatment matters, and clinicians increasingly want evidence on how the available options compare,” he added.
Apart from the core weight loss results, Lilly also linked 15-mg Zepbound to a fourfold increased likelihood of patients achieving 20% or greater body weight reduction versus Wegovy HD on the efficacy estimand and three-times more likely using the treatment-regimen estimand, which accounts for results regardless of whether a participant stopped therapy.
“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,” said Thomas Seck, SVP of product development for Lilly cardiometabolic health, in a statement.
He was referring to Lilly’s Surmount-5 study, which directly pitted Zepbound against Wegovy and read out in tirzepatide’s favor in late 2024.
In that trial, Lilly linked its medicine to a 47% greater relative weight loss than Wegovy at 72 weeks on the treatment-regimen estimand. Participants on Zepbound lost an average of 50.3 pounds over that span, compared to 33.1 pounds in the Wegovy cohort.
Though the results shared this week don’t seem to significantly move the needle for companies’ franchise, the two companies’ efforts to reinforce their GLP-1s’ unique benefits affirm the continued competition in the metabolic health space.
Meanwhile, finding unique features to pin one’s GLP-1 pitch on has become increasingly important both for developers hoping to catch the next wave of obesity treatments and for Novo’s and Lilly’s marketed products, which have found themselves playing in an increasingly consumer-like market that is largely unique to branded, prescription medicines.