At this year’s meeting of the European Association for the Study of Diabetes (EASD) in Vienna, Eli Lilly sought to bolster the case for its oral GLP-1 orforglipron, showcasing more of the drug's benefits for patients with obesity and providing evidence that its medicine can go toe-to-toe with a rival from Novo Nordisk in diabetes.
To the first point, Lilly has dropped detailed results on its phase 3 Attain-1 study of orforglipron in adults with obesity and certain individuals who are overweight, adding color to the top-line data it reported in early August. With a complete data set in hand, Lilly is now advancing the drug toward global regulatory submissions and said in a press release that it expects obesity approvals for the candidate could start rolling in “as early as next year.”
Separately, Lilly has disclosed data from its Achieve-3 study, which pitted orforglipron against an oral version of semaglutide—the molecule behind Novo’s GLP-1s Ozempic, Reybelsus and Wegovy—in patients with Type 2 diabetes whose disease isn’t adequately controlled by metformin.
Detailed obesity readout
On the obesity front, Lilly reported last month that orforglipron helped patients lose an average of 27.3 pounds, or 12.4%, of their body weight at 72 weeks. While that performance allowed the Attain-1 study to meet its goal, it was below what some analysts had hoped for, despite Lilly’s science chief stating on a conference call that “[t]his is as good as it gets for GLP-1 monotherapy” in a once-a-day pill.
The study enrolled adults with obesity or who are overweight with a weight-related medical problem and without diabetes.
Lilly elaborated on the study results Tuesday, noting that orforglipron at its highest, 36-mg dose helped 18.4% of patients lose at least 20% of their body weight compared to just 2.8% of patients in the trial’s control arm. Patients on the 36-mg dose of Lilly’s drug reduced their waist circumference by an average of 4 inches from a baseline of 44.25 inches, compared to a 1.2-inch reduction in the placebo group.
The data issued Tuesday also offer further detail on orforglipron’s potential to tackle known markers of cardiovascular risk like non-HDL cholesterol, triglycerides and systolic blood pressure, too.
Patients on the highest orforglipron dose experienced an average 7.7% drop in non-HDL cholesterol levels, a 20.2% average reduction in triglyceride levels and a 6.3-mm Hg average drop in systolic blood pressure, compared to 1.9%, 3.8% and 1.4-mm Hg reductions among patients on placebo, respectively.
“People living with obesity have broad and varied needs—whether it’s improving weight, A1C, lipids, blood pressure, or other health markers that primary care physicians routinely address with their patients,” Kenneth Custer, Ph.D., executive vice president and president of Lilly cardiometabolic health, said in a statement.
While the first slate of approved GLP-1s for obesity are formatted as injections, a pill like orforglipron could be easier to produce en masse and would place less of a burden on patients, Custer added.
“As a convenient, once-daily pill that can be scaled globally, orforglipron could be ideally suited for early adoption in primary care—where proactive intervention has the potential to lead to meaningful, long-term health improvements,” he said.
As competition in obesity starts to head for the oral arena, Lilly will likely enter the market with orforglipron second behind Novo Nordisk.
Back in May, Novo submitted an oral version of its semaglutide med Wegovy for FDA approval, with a regulatory decision now expected sometime in 2025’s fourth quarter. Oral Wegovy has been shown to help patients achieve average weight loss of 16.6%, above the 12.4% reduction charted by orforglipron. That said, cross-trial comparisons are an imperfect snapshot of how the drugs performed in their respective studies and don't account for differences in trial populations, among other factors.
Aside from Novo and Lilly, other developers like Viking Therapeutics are also trying their hands at oral obesity assets, albeit with mixed results.
Diabetes head-to-head result
Meanwhile, not content to let orforglipron play in obesity alone, Lilly on Wednesday served up semaglutide-topping results from a head-to-head trial of its oral asset in patients with Type 2 diabetes who aren’t able to control their disease with metformin.
Overall, the head-to-head study, dubbed Achieve-3, met its primary endpoint and all key secondary objectives, with orforglipron besting semaglutide on improvements in blood sugar and weight, Lilly said in a release.
Specifically, at the trial’s one-year mark, orforglipron at 12-mg and 36-mg doses helped lower patients’ A1C by an average of 1.9% and 2.2%, respectively, versus 1.1% and 1.4% reductions observed in patients taking 7-mg and 14-mg doses of semaglutide.
The 7- and 14-mg semaglutide doses included in Lilly’s trial match those of Novo’s Rybelsus, an oral version of the GLP-1 semaglutide that is approved as a first-line treatment option in Type 2 diabetes. Novo’s oral Wegovy filing for obesity is separate from Rybelsus, which first won FDA sign-off in 2019 before scoring a label expansion in 2023.
Further, 37.1% of patients on the highest orforglipron dose achieved an A1C of less than 5.7%, compared to just 12.5% of patients on the highest dose of semaglutide, Lilly noted. Lilly’s drug also bested Novo’s at helping diabetes patients lose weight.
“In this type 2 diabetes trial, orforglipron, even at the lower dose, outperformed both doses of oral semaglutide in reducing A1C,” Lilly’s Custer said in the Achieve-3 release. “At the highest dose, orforglipron helped nearly three times as many participants reach near-normal blood sugar versus the highest dose of oral semaglutide.”
Lilly is first angling for an orforglipron approval in obesity before setting its sights on diabetes.
The company said Wednesday that it plans to present detailed results from Achieve-3 at an upcoming medical meeting, with the expectation that it will submit the pill for approval in Type 2 diabetes sometime next year.