What to Know About Orforglipron, the Emerging Oral GLP-1
As a clinical phrmacist, you will get questions about orforglipron (Foundayo), the second ORAL GLP-1 receptor agonist approved for adults with overweight or obesity. It’s another DAILY option, like oral semaglutide (Wegovy). But orforglipron can be taken with or without food. Oral semaglutide must be taken with a max of 4 oz of water at least 30 minutes before the first food, other beverage, or oral medications of the day.
That’s because orforglipron is a nonpeptide, small molecule drug, other GLP-1s are peptides that can be broken down by stomach acid. Studies report that taking one orforglipron 36 mg capsule daily for 72 weeks leads to about 9% more weight loss than placebo. But only orforglipron tablets are approved and available. Unpublished data show that the 36 mg capsules and the 17.2 mg tablets are equivalent, providing comparable blood levels.
Weight loss with orforglipron seems in the same ballpark as oral semaglutide 25 mg/day, which leads to about 11% more weight loss than placebo. But these 2 medications haven’t been directly compared for weight loss. Orforglipron is not approved for type 2 diabetes yet, but one 36 mg capsule (or 17.2 mg tablet) daily lowers A1c by about 1% more than placebo and about 0.4% more than oral semaglutide 14 mg daily.
Tell patients starting orforglipron to follow the titration to limit GI side effects (e.g., nausea, diarrhea, abdominal pain). Orforglipron tablets are available in 6 strengths starting at 0.8 mg daily with monthly titration up to the max dose of 17.2 mg/day.
Be aware of interactions. For instance, orforglipron 9 mg is the max dose when used with strong CYP3A4 inhibitors (e.g., clarithromycin) and it shouldn’t be used with strong CYP3A4 inducers (e.g., carbamazepine). Plus it carries the same warnings as other GLP-1s, including rare thyroid tumors, pancreatitis, and gallbladder disease.
Expect prior authorization requirements for Orforglipron, an emerging oral GLP-1 therapy projected to cost less than oral Semaglutide. Patients may benefit from manufacturer savings or direct-to-consumer programs. Ongoing research is evaluating Orforglipron for cardiovascular risk reduction, Type 2 Diabetes management, and long-term weight maintenance after injectable GLP-1 therapy.
References
- Wharton S, Blevins T, Connery L, et al. Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. N Engl J Med. 2023;389(10):877-888.
- Wharton S, Aronne LJ, Stefanski A, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. N Engl J Med. 2025;393(18):1796-1806.
- Rosenstock J, Hsia S, Nevarez Ruiz L, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes. N Engl J Med. 2025;393(11):1065-1076.
