Eli Lilly's experimental weight-loss pill, orforglipron, achieved up to 12.4% weight loss at the highest dose in its first pivotal Phase 3 trial—but the results came in below investor expectations. Although the 72-week trial met both primary and key secondary endpoints, the data lag behind injectable competitors such as Lilly’s Zepbound (20.2%) and Novo Nordisk’s Wegovy (17.5%–20.7%).
Importantly, orforglipron’s results also fall short of oral semaglutide 25 mg, which showed a 13.6% weight reduction at 64 weeks in a separate Phase 3 study. That dose is currently under FDA review, with potential approval expected in the fourth quarter of this year. The market had anticipated orforglipron would outperform existing oral options, but those expectations have now been tempered.
Despite the edge in efficacy, oral semaglutide comes with strict administration requirements—it must be taken on an empty stomach with no more than 4 ounces of water, followed by a wait of at least 30 minutes before eating or drinking anything else. Orforglipron has no such restrictions, offering a potentially more convenient, once-daily oral option that may improve adherence and long-term persistence. This difference could become a key factor in patient preference and real-world use, even if semaglutide retains an advantage on weight loss outcomes.
Following the data release, Lilly shares fell nearly 8% in premarket trading. In contrast, Novo Nordisk surged as much as 14%, reflecting renewed confidence in its obesity franchise.
Lilly plans to submit orforglipron for global regulatory approval by year-end and is investing in manufacturing capacity to meet expected demand. Full trial results will be presented next month at the European Association for the Study of Diabetes (EASD) annual meeting.
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