Eli Lilly’s Experimental Pill Could Help You Ditch GLP-1 Obesity Shots, Trial Finds

Good news for people on GLP-1 therapy who hate needles: Trial data out this week shows that an experimental pill developed by Eli Lilly could offer an intriguing off-ramp.

On Thursday morning, Eli Lilly presented the results of its latest phase III trial of the drug, named orforglipron. People taking the once-daily pill were largely able to keep off the weight they originally lost taking a different GLP-1 injectable. The company is already seeking the FDA’s approval of orforglipron, which could occur by early next year.

A different take on obesity treatment

GLP-1 drugs like semaglutide (the active ingredient of Ozempic and Wegovy) and tirzepatide (Zepbound and Mounjaro) have revolutionized obesity treatment in recent years. But both have their potential drawbacks. For many, that can include the need for a weekly subcutaneous injection.

There is one GLP-1 treatment currently available in pill form, Novo Nordisk’s semaglutide-based drug Rybelsus, but it’s only approved for type 2 diabetes. Eli Lilly is banking on its experimental pill to entice potential users; not only does orforglipron do away with needles, it can also be taken without any restrictions, unlike Rybelsus (the latter is supposed to be taken in the morning, at least 30 minutes before eating or drinking).

Earlier this August, the company presented the results from its first phase III trials of orforglipron that tested it as a front-line obesity treatment. The drug performed significantly better than a placebo, with people on the highest dose losing around 10% of their baseline body weight on average. These results, while successful, weren’t quite as impressive as many had hoped. For some context, the most potent injectable drugs in development today have helped people achieve up to 28% weight loss.

The company’s latest findings, however, might point to another promising avenue for orforglipron—as a treatment for maintaining the weight lost with other drugs.

The maintenance pill

The ATTAIN-MAINTAIN trial involved participants from the company’s earlier SURMOUNT-5 study, which directly compared semaglutide and tirzepatide. At the end of the original 72-week study, people on the highest dose of either medication were randomized into two arms: the treatment group taking a once-daily dose of orforglipron and a placebo control group.

All in all, the placebo group fared far worse than those on orforglipron. At 24 weeks (the last point before people taking a placebo were eligible to switch to orforglipron), people taking a placebo had roughly gained 20 pounds back on average, no matter which drug they were taking originally. But those taking orforglipron experienced much less weight regain.

On average, people taking semaglutide lost around 40 pounds before starting orforglipron and only gained an average two pounds back one year later. People on tirzepatide lost about 50 pounds originally and gained an average ten pounds back after switching to orforglipron. The experimental drug also appeared to be safe and tolerable, with adverse events similar to other GLP-1 drugs (mostly gastrointestinal and mostly mild to moderate in severity).

The future of orforglipron

Given the unambiguous results of this and other late-stage trials, orforglipron should have an easy path to regulatory approval. The FDA is expected to issue its decision by no later than March 2026.

It’s likely there will be several populations who can benefit from the drug once approved. Some people might be okay with its relatively modest weight loss effects in exchange for the convenience of a pill. Yet others might switch to orforglipron once they’ve lost weight with a more powerful GLP-1 drug.

“If approved for the treatment of obesity, orforglipron could provide a convenient alternative for the millions of individuals living with obesity around the globe to continue their long-term health journey,†said Kenneth Custer, executive vice president at Eli Lilly and president of Lilly Cardiometabolic Health, in a statement from the company.

Orforglipron is only one of several next-generation GLP-1 drugs that are expected to reach the public in the near future. Of course, these meds aren’t cheap, so hopefully these new drugs and all this competition will result in some lower prices.