Lilly ends two of three mid-stage trials of its second oral GLP-1

Eli Lilly has ended two of three phase 2 trials testing naperiglipron, an experimental oral GLP-1 pill, while keeping its lead oral drug orforglipron on track for a regulatory filing this year ^[1][2]. The company narrowed its oral pipeline to focus on orforglipron as that drug moves closer to a possible FDA decision ^[1].

The two discontinued studies were both listed as stopped for "strategic business reasons" on federal trial registries ^[1][2]. One trial had planned to enroll 150 people with overweight or obesity and type 2 diabetes, but only one patient signed up ^[2]. The other aimed to enroll 220 adults ages 55 to 80 with a body mass index between 22 and 25, and it also enrolled just one patient ^[2]. Both studies had started over the summer and were originally set to run about a year ^[1].

A third phase 2 study of naperiglipron is still recruiting. It aims to enroll 275 people with overweight or obesity, giving them the pill or a placebo once a day, with a primary completion date of April 2026 ^[1][2]. Lilly says results from this remaining trial "will inform the next steps for this program" ^[1][2]. The company declined to give more detail beyond the "strategic business reasons" cited in the trial records ^[1].

Naperiglipron shares a chemical design, or scaffold, with two other oral obesity drugs that Pfizer dropped after safety problems: danuglipron and lotiglipron ^[2]. Analysts at BMO Capital Markets noted in June that this shared history raises questions about whether Lilly can avoid the same pitfalls, though they also said naperiglipron could help diversify Lilly's oral obesity lineup if it succeeds ^[2].

The trial cuts come as Lilly reports new data on orforglipron, its more advanced oral GLP-1 pill. In the phase 3 ATTAIN-1 trial, the highest dose of orforglipron produced an average weight loss of 12.4%, or about 27.3 pounds, in people with obesity or overweight who did not have diabetes ^[1][2]. That fell short of some investors' expectations, and Lilly's stock dropped 13% the day the data came out ^[1]. A separate phase 3 trial called ATTAIN-2, in patients with type 2 diabetes, showed a 10.5% average weight reduction along with lower blood sugar and improved cardiometabolic risk factors at 72 weeks ^[1][2]. Truist Securities analysts called those results "in-line" with expectations but said they leave "room for competition" ^[2].

For comparison, Novo Nordisk's injectable drug CagriSema has shown 15.7% weight loss in trials, a benchmark that has shaped how investors judge Lilly's oral results ^[1]. Lilly's chief scientific officer, Daniel Skovronsky, defended orforglipron's data as "as good as it gets for GLP-1 monotherapy" in the once-daily pill category ^[1].

Why it matters for patients

For people hoping for a pill alternative to injectable GLP-1 drugs, orforglipron remains the company's most advanced option, and it is still on track for a regulatory filing this year ^[1][2]. The narrowing of the naperiglipron program does not change availability of any approved drug today; naperiglipron was still in mid-stage testing and was not close to being sold. Patients should know that early trial data on new oral GLP-1 drugs can shift, and that a drug's design similarity to previously discontinued drugs, as analysts flagged for naperiglipron, is a factor companies and regulators watch closely for safety signals ^[2]. The weight-loss numbers reported so far for orforglipron, 12.4% and 10.5% in two different patient groups, are lower than the 15.7% seen with Novo Nordisk's CagriSema in trials, which may matter to people comparing potential future options ^[1].

What happens next

The remaining naperiglipron phase 2 trial has a primary completion date of April 2026 and will determine whether Lilly continues developing the drug ^[1][2]. Lilly has said it plans a regulatory filing for orforglipron this year, following the ATTAIN-1 and ATTAIN-2 phase 3 results ^[1][2].