Participants in a Phase III trial who switched to Eli Lilly’s orforglipron after 72 weeks of treatment with Wegovy or Zepbound largely maintained their weight loss for up to a year.
Maintenance treatment with Eli Lilly’s experimental oral obesity medicine orforglipron helped patients sustain the weight they lost from an initial round of GLP-1 therapy after a year.
These findings come from the Phase III ATTAIN-MAINTAIN trial, which enrolled participants who had undergone 72 weeks of initial treatment with either Novo Nordisk’s Wegovy or Lilly’s Zepbound. After re-randomizing, these individuals were then transitioned to daily oral orforglipron or placebo and followed for 52 more weeks.
At the time of their switch to orforglipron, patients moving from Wegovy had an average weight of 95 kg (209.4 lbs), which increased only slightly to 95.9 kg (211.4 lbs) at the 1-year follow-up, according to Lilly’s Thursday news release. Meanwhile, participants switching from Zepbound weighed an average of 90.9 kg (200.4 lbs) at the start of their oral maintenance regimen, increasing to 95.9 kg after 52 weeks (211.4 lbs).
In a Thursday morning to investors, Truist analysts wrote that the study’s results were “in-line with our expectations that orforglipron is able to maintain significant weight loss for patients over an extended period given prior use of Wegovy or Zepbound.
“We think the data support use of orforglipron as a maintenance therapy that will appeal to many individuals who prefer a convenient oral daily pill to achieve their ongoing weight loss goals,” the analysts added.
The data could also hurt Novo’s prospects in the obesity space, according to analysts at BMO Capital Markets. “All in, today’s data is supportive of increased orforglipron uptake, setting Lilly up for continued future growth at Novo’s expense,” they wrote in a note to investors Thursday morning.
Orforglipron is Lilly’s horse in the increasingly competitive oral obesity race, where it is primarily going against a pill version of Wegovy. Novo is poised to narrowly win the race to market—its new drug application was accepted in May, and BMO analysts in their Thursday note said they expect a decision by the end of 2025.
Lilly, meanwhile, confirmed in its Thursday release that it has filed an application with the FDA and, according to analysts at William Blair, has an action date in March 2026. Last month, the FDA granted orforglipron its Commissioner’s National Priority Voucher, which could cut down the review time to 1–2 months, from the standard 10–12 months.
With this ticket, some analysts anticipate orforglipron could be approved before the end of the year.
Regardless of which pill crosses the regulatory finish line first, orforglipron has already established itself in the clinic. This year alone, the drug has already delivered a series of late-stage victories. In August in the Phase III ATTAIN-2 study, for instance, orforglipron achieved 10.5% weight loss at 72 weeks versus 2.2% in placebo.
Then, in September, orforglipron emerged as the winner in a head-to-head study against an oral version of Novo’s Wegovy. But this time, instead of focusing on weight-loss, the Phase III ACHIEVE-3 trial enrolled patients with type 2 diabetes and looked primarily at the drugs’ effect on blood sugar levels. Orforglipron cut A1C by 1.9% on average, versus 1.7% in the semaglutide group. The study also looked at body weight as a secondary endpoint, showing stronger weight-loss with orforglipron.
A month later, orforglipron again came out on top when compared against AstraZeneca’s diabetes drug Farxiga.
