A new oral weight loss medication, orforglipron, has shown promising results in phase 3 trials, potentially offering a more convenient alternative to injectable GLP-1 medications like Ozempic and Wegovy. The Eli Lilly drug demonstrated ‘meaningful weight loss’ and various cardiometabolic improvements in adults with weight-related medical conditions but no diabetes.
The phase 3 ATTAIN-1 trial, published in the New England Journal of Medicine, involved 1,127 participants who were treated for 72 weeks with three different doses of orforglipron (6 mg, 12 mg, and 36 mg). Results indicated that participants who received the highest dose lost an average of 27.3 pounds, with nearly 60% losing 10% of their body weight and 39.6% losing at least 15%. Additionally, up to 91% of participants with pre-diabetes achieved nearly normal blood sugar levels compared to 42% in the placebo group, according to the study.
Orforglipron also demonstrated improvements in cardiovascular risk factors associated with obesity, including non-HDL cholesterol, systolic blood pressure, and triglycerides. The drug’s safety profile is similar to existing GLP-1 medications, with the most common side effects being gastrointestinal issues like nausea, constipation, and diarrhea at mild to moderate severity.
Dr. Sean Wharton, the lead study author and director at Wharton Medical Clinic, highlighted the importance of having effective and easy-to-integrate weight loss treatments in daily life. He stated that the trial results reinforce orforglipron’s potential as a first-line treatment in primary care and its ability to support meaningful public health improvements.
Lilly is moving forward with plans to seek FDA approval for orforglipron as an obesity medication, with potential approval by 2026. The company also aims to apply for approval for its use in treating type 2 diabetes in the same year. Analysts have speculated that the drug may be fast-tracked under a one- to two-month review process launched by the FDA, citing the rising costs of injectable weight-loss drugs and the Trump administration’s focus on expanding U.S. manufacturing.
While medical experts like Sue Decotiis, a weight loss doctor in New York, view orforglipron as a useful addition to weight loss options, she also emphasized that its results may not surpass those of injectable medications such as Ozempic and Mounjaro. She noted that orforglipron’s oral administration may improve compliance but raised concerns about its safety profile due to its non-peptide nature, which could lead to unknown long-term consequences.
This development has sparked discussions about the future of weight loss treatments, with expectations for more oral options to emerge. As Eli Lilly continues to push for approval and potential use in diabetes treatment, the pharmaceutical industry remains focused on improving patient outcomes and accessibility to effective weight management solutions.