Oral GLP-1 weight-loss pill shows promise as potential replacement for Ozempic and Wegovy

An oral GLP-1 weight‑loss drug, orforglipron, showed meaningful weight loss and cardiometabolic improvements in a phase 3 trial, raising the possibility it could replace injectable therapies such as Ozempic and Wegovy for some patients. The ATTAIN-1 study evaluated 1,127 adults with weight-related conditions who did not have diabetes over 72 weeks, testing three doses: 6 mg, 12 mg and 36 mg. At the end of treatment, participants at the highest dose lost an average 27.3 pounds. About 60% lost at least 10% of body weight and 39.6% achieved at least 15% weight loss.

Among participants with pre-diabetes at baseline, up to 91% achieved near-normal blood sugar levels compared with 42% on placebo. Orforglipron also produced clinically meaningful improvements in cardiovascular risk factors associated with obesity, including non-HDL cholesterol, systolic blood pressure and triglycerides. The most common adverse events were gastrointestinal and generally mild to moderate, such as nausea, constipation, diarrhea and vomiting. In the long-term extension, those on the highest dose lost an average of 27.7 pounds after more than a year of use.

The trial was led by Sean Wharton, M.D., director at Wharton Medical Clinic, who noted obesity is a complex, global health challenge that requires treatment options that are effective and easy to integrate into everyday life. In this phase 3 study, orforglipron demonstrated strong efficacy results and safety consistent with the GLP-1 class, reinforcing its potential as a first-line treatment in primary care and the potential to reduce cardiovascular risk markers.

Lilly said it plans to pursue regulatory approval for orforglipron as an obesity drug and could seek a verdict as early as 2026. The company also expects to file for approval to use the drug to treat type 2 diabetes in the same year. Reuters reported that the FDA could fast-track the review with a one- to two-month process, a trajectory analysts linked to cost pressures from injectable weight-loss drugs and Lilly's expanding U.S. manufacturing.

Industry and clinical experts offered cautious optimism. In interviews, physicians noted that a pill form could improve patient adherence and reduce costs, but acknowledged that injectable GLP-1 medications often show stronger weight-loss results. Dr. Sue Decotiis, a medical weight-loss specialist, called orforglipron a positive addition to treatment options but cautioned that results may not match injectable therapies. She noted that it is not a peptide, which has a favorable safety profile and metabolizes easily, and warned there could be unknown long-term effects. She also predicted more oral weight-loss drugs in development and hoped some would be in the peptide category.

Overall, orforglipron adds to a growing field of GLP-1–based weight-loss therapies explored by major pharma companies. The NEJM publication underscores the potential for oral options to broaden access and simplify treatment, though questions about long-term safety and real-world effectiveness remain as Lilly proceeds with regulatory submissions.