Orforglipron — brand name Foundayo — is an oral, non-peptide, small-molecule GLP-1 receptor agonist developed as a weight loss drug by Eli Lilly and Company. It was discovered by Chugai Pharmaceutical Co., then was licensed to Lilly in 2018.
Orforglipron was approved for medical use in the United States in April 2026. It was approved for use in the UK in August 2026.
Medical uses Orforglipron is indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition.
Adverse effects Safety and dosing trials showed that the incidence of adverse events in orforglipron-treated participants was 62–89%, mostly from gastrointestinal discomfort (44–70% with orforglipron, 18% with placebo); in patients experiencing adverse events, 96% had mild to moderate GI side effects, while approximately 4% had severe nausea or vomiting. The most common side effects of orforglipon noted in clinical trials were vomiting, diarrhea, nausea, upset stomach, and constipation.
Mechanism of action Orforglipron is a small-molecule, partial GLP-1 receptor agonist affecting the activity of cyclic adenosine monophosphate (cAMP); its effects are similar to the actions of glucagon-like peptide-1 (GLP-1) for reducing food intake and lowering blood glucose levels.
Clinical trials The results of Phase I safety and Phase II ascending-dose clinical trials enrolling people with obesity or type 2 diabetes were published in 2023.
The ability of orforglipron to reduce blood sugar levels and body weight was judged favorable compared to dulaglutide.
Phase III ACHIEVE-1 trial
In April 2025, results from a phase III clinical trial involving 559 people with type 2 diabetes who took an oral orforglipron pill or a placebo daily for 40 weeks showed that orforglipron produced a reduction of hemoglobin A1C level by 1.3 to 1.6 percentage points from a starting level of 8%.
More than 65% of participants taking the highest dose of orforglipron achieved a reduction of hemoglobin A1C level by more than or equal to 1.5 percentage points, bringing them into the non-diabetic range as defined by the American Diabetes Association. People taking the highest dose of the pill lost 8% of their weight, or around , on average after 40 weeks. In its press release, Lilly noted that the subjects' weight loss had not yet plateaued at the time the trial concluded, and suggested that this indicated that greater weight reduction would ultimately be achieved with extended therapy.
Side effects were similar to those seen with other GLP-1 agonists, and no significant liver problems were observed.
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