GLP-1 receptor agonists are now well established as weight-loss treatments, but until recently, they have been available exclusively as injections. 

Lilly, headquartered in Indianapolis, announced that the oral GLP-1 receptor agonist orforglipron reduced the average body weight by 12.4% in a phase 3 trial.

The effect was comparable to that seen with injectable semaglutide, and German experts remain cautious about the findings.

“The results show that the oral GLP-1 receptor agonist orforglipron leads to a more than 10% reduction in body weight compared to placebo. This reduction is only slightly lower than that achieved with semaglutide, which must be injected weekly. There are also no significant differences in side effects,” said Stephan Martin, MD, chief physician for diabetology and director of the West German Diabetes and Health Center, Düsseldorf, Germany, in a statement to the Science Media Center, Germany.

Trial Design

The ATTAIN-1 trial enrolled 3127 adults with obesity (BMI ≥ 30) or overweight (BMI ≥ 27) with at least one weight-related comorbidity. 

Participants were randomly assigned to receive orforglipron at doses of 6 mg, 12 mg, or 36 mg, or to a placebo. All groups received counselling on healthy eating and regular physical activity.

Weight Reduction

At 72 weeks, patients receiving 36 mg of orforglipron lost an average of 12.4% of body weight (-12.4 kg) compared with 0.9% (-1 kg) with placebo. In the highest-dose group, 59.6% lost at least 10%, and 39.6% lost at least 15%.