Is Orforglipron the first GLP-1 weight loss pill?

Yes, if Eli Lilly’s orforglipron is eventually approved by the FDA, it will be the first oral GLP-1 drug specifically indicated for weight loss. Novo Nordisk has an oral GLP-1 drug, Rybelsus (semaglutide) on the market, but it is only approved for type 2 diabetes.

While Rybelsus is sometimes used off-label for weight loss, it produces about half the weight loss of orforglipron, on average. Orforglipron also comes with no water or food or restrictions, while people must take Rybelsus 30 minutes before eating or drinking and must limit their consumption of certain foods. One Phase 2 trial that included obese adults with at least one weight-related comorbidity (not including type 2 diabetes) saw participants lose an average of 14.7% of their body weight at 36 weeks. This is similar to injectable GLP-1s like Wegovy (semaglutide).

The results of the first Phase 3 trial with orforglipron also showed promising results in obese people with type 2 diabetes. At 40 weeks, orforglipron lowered A1C levels by an average of 1.3% to 1.6% from a baseline of 8.0%. And more than 65% of those taking orforglipron reached an A1C level that was less than or equal to 6.5%, which is below the American Diabetes Association’s (ADA) defined threshold for diabetes. Orforglipron also led to an average weight loss of 16.0 lbs (7.9%) at the highest dose, which is 36 mg. It is thought that this weight loss had not plateaued so participants might lose even more weight if it is taken for longer.
Orforglipron was generally well-tolerated with the most common adverse events being GI-related and mild to moderate. Given it is a GLP-1, this was to be expected. The most common side effects of orforglipron reported were diarrhea, nausea, indigestion, constipation, and vomiting.

Several other Phase 3 trials are currently underway. Lilly expects to seek approval for weight management by the end of this year, with the submission for the treatment of type 2 diabetes anticipated in 2026.

Source

• Lilly’s oral GLP-1, orforglipron, demonstrated statistically significant efficacy results and a safety profile consistent with injectable GLP-1 medicines in successful Phase 3 trial. Eli Lilly. Accessed June 9, 2025.