A daily oral GLP-1 pill, known as orforglipron and developed by Eli Lilly, has shown it can help people with obesity achieve approximately 12% body weight loss, according to preliminary data released today.
This medication could be a favorable alternative to injectable GLP-1 drugs since it may be easier to manufacture and distribute.
“Orforglipron could facilitate early intervention and long-term disease management while offering a convenient option over injectables,” remarked Kenneth Custer, PhD, executive vice president at Lilly Cardiometabolic Health.
However, Eli Lilly's results today suggest that orforglipron produces considerably less weight loss compared to drugs like Wegovy and Zepbound, which can result in 15% to 25% body weight reduction.
Wajahat Mehal, MD and director of the Weight Loss Program at Yale School of Medicine, commented: “The results for orforglipron appear quite weak in comparison. Instead of asking why someone would use this drug, the real question becomes why they wouldn't opt for a more effective alternative instead.”
Orforglipron is designed as a tablet taken once daily and works by activating GLP-1 hormones in the gut, similar to injectables. It helps manage body functions such as hunger, appetite, and insulin secretion.
If approved by regulatory authorities, orforglipron would be the first oral GLP-1 drug that doesn't have restrictions on eating or drinking beforehand—unlike Novo Nordisk’s current oral option, Rybelsus, which must be taken on an empty stomach and followed by a 30-minute wait before consuming anything.
Today’s results come from one of two phase 3 trials testing orforglipron in non-diabetic individuals. The Attain-1 study, lasting 72 weeks and involving over 3,000 participants with obesity or weight-related medical issues, found that the highest tablet dose (36 milligrams) led to an average body weight loss of 12.4%.
Although these results are an average outcome, indicating not all participants reached this mark even at maximum dosage.
At lower doses—12 and 6 milligrams—the average weight loss was 9.3% and 7.8%, respectively, comparable to older GLP-1 medications like Contrave.
Eli Lilly also reported improvements in cardiovascular risk markers such as non-HDL cholesterol, triglycerides, and systolic blood pressure across various dosages.
The company plans to present full results at a conference later this month and intends to file for FDA approval by the end of the year.
In a prior study involving diabetics, Lilly found that participants on the highest dose of orforglipron lost 8% body weight after 40 weeks. Generally, individuals without diabetes tend to see greater weight loss benefits from GLP-1 drugs than those with diabetes.
The press release noted that orforglipron’s safety profile is similar to injectable GLP-1 drugs like Zepbound and Mounjaro, with most side effects being mild gastrointestinal issues.
Custer previously mentioned oral options could be important for the approximately 75% of patients who prefer avoiding needles.
Mehal suggested that despite modest weight loss results and potential side effects like vomiting (experienced by a quarter of participants), some might still view it as an alternative, particularly if combined with existing injectable treatments or as a cheaper maintenance option post-substantial weight loss.
The company is also testing orforglipron's effectiveness as a maintenance drug in the ongoing Surmount-5 study.