What are the pros and cons of taking Orforglipron?

Orforglipron is an investigational oral GLP-1 medication that is being developed by Eli Lilly as a possible treatment for obesity and type 2 diabetes. Some pros and cons of taking orforglipron based on the available clinical trial data include:

Pros

Orforglipron is taken by mouth once daily as a pill, without regards to food and water intake. This eliminates the need for injections, making it a more convenient option for many people. Injectables have to be stored in the refrigerator, so transportation of the medication is also easier.

Clinical trials have shown that orforglipron can lead to signifcant weight loss, with participants losing up to 14.7% of their body weight over 36 weeks. These people were obese and had at least one weight-related comorbidity other than type 2 diabetes. Participants on higher doses in a different Phase 3 trial lost an average of 16 pounds or 7.9% of their body weight. These people were obese and had type 2 diabetes.

Orforglipron has been shown to be effective in lowering A1C levels (a measure of blood sugar control), with reductions that are similar to or better than other GLP-1 medications. In one clinical study, over 65% of people on the highest dose of orforglipron reached an A1C of 6.5% or less.

The side effect profile seems to be consistent with other GLP-1 medications, with most being mild to moderate GI issues like nausea, vomiting, indigestion, and constipation.

Cons

Orforglipron is still in clinical trials and has not been approved by the FDA. It is currently in several other Phase 3 trials. Lilly expects to seek approval to treat obesity around the end of this year and in 2026 for type 2 diabetes.
While these initial results are promising, long-term safety and efficacy data is still being collected. So, it is not known what serious side effects that may occur with orforglipron.

Some studies suggest that the GI side effects of orforglipron may be more common when compared to injectable GLP-1 medications.

Sources

Lilly’s phase 2 results published in the New England Journal of Medicine show orforglipron, a once-daily oral nonpeptide GLP-1 receptor agonist, achieved up to 14.7% mean weight reduction at 36 weeks in adults with obesity or overweight. Eli Lilly. Accessed June 9, 2025.
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.