Eli Lilly's oral GLP-1 receptor agonist, orforglipron, has demonstrated significant weight loss in a phase 3 trial, reducing average body weight by 12.4%, which is comparable to injectable semaglutide.

The ATTAIN-1 trial involved over 3,100 overweight or obese adults, with doses of 6 mg, 12 mg, and 36 mg of orforglipron, showing that the highest dose led to over 59% of participants losing at least 10% of their body weight.

Eli Lilly plans to submit orforglipron for regulatory approval worldwide by the end of 2025, with detailed results to be presented at the European Association for the Study of Diabetes meeting in September.

The weight loss achieved with orforglipron also resulted in improvements in cardiovascular risk markers, including lowered cholesterol, triglycerides, blood pressure, and a 47.7% reduction in high-sensitivity C-reactive protein levels.

Adverse effects were mainly gastrointestinal, such as nausea, vomiting, diarrhea, and constipation, with discontinuation rates increasing at higher doses, reaching 24.4% in the 36 mg group.

While experts, including Dr. Stefan Kabisch, acknowledged the findings as noteworthy, they considered them similar to existing injectable therapies, and warned that discontinuation could lead to weight regain and muscle loss.

The potential cost and accessibility of the oral medication, along with logistical challenges like counseling support, will play a crucial role in its adoption.

There are concerns about the misuse of the pill by individuals with only slightly elevated BMI and a possible shift from nutritional therapies to symptom management.