Orforglipron

The United States Food and Drug Administration approved orforglipron as Foundayo, a tablet from Eli Lilly and Company, under new drug application 220934 on April 1, 2026. The approved use is chronic weight management: 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 in adults with overweight who also have at least one weight-related comorbid condition. Type 2 diabetes is not an approved indication for this product, and the label's Limitations of Use state that concomitant use with another GLP-1 receptor agonist is not recommended.^[3][2]

Jurisdiction

United States

Product

Foundayo (orforglipron) tablets, new drug application 220934, Eli Lilly and Company

Indication

Chronic weight management in adults with obesity, or adults with overweight and at least one weight-related comorbid condition; not approved for type 2 diabetes

Record date

2026-09-08 · Approved 2026-04-01

• This is a United States status for one named product. It says nothing about the status of orforglipron in any other jurisdiction, or about any unapproved product sold under this name.
• That an indication is not approved is a statement about the regulatory record, not a finding that the drug does not work for that condition. A separate phase 3 trial in type 2 diabetes is recorded elsewhere in this reference.
• The recorded date is the date through which the status was confirmed still current, and it is capped at the evidence cutoff. It is not the date of either cited document. The currency check behind it, made on 2026-09-09 against the agency's own application record and against the labeling posted at that time, is recorded in the correction checks on the two cited source records rather than restated as a finding here.

Orforglipron is a small-molecule, nonpeptide agonist of the GLP-1 receptor taken by mouth, which distinguishes it from the injected peptide GLP-1 receptor agonists. Laboratory work reported by its developers describes it as a high-affinity, selective ligand of the human GLP-1 receptor with low intrinsic efficacy for effector activation and negligible beta-arrestin recruitment, and reports that low occupancy of the receptor was enough to produce a full biological response in mice carrying the human receptor. The approved United States product is a tablet for oral use.^[1][2]

• The receptor and rodent findings come from an abstract read without its methods or figures, and were reported by the molecule's developers. They describe target engagement in the laboratory, not clinical effects.
• Being a nonpeptide molecule is a chemical fact about this compound. It is not by itself a safety, tolerability or efficacy advantage over peptide agents, and none was established by the sources inspected here.

The approved United States label carries a boxed warning about the risk of thyroid C-cell tumors. It states that rodent thyroid C-cell tumors have been observed with products that have GLP-1 receptor agonist activity and are pharmacologically active in rats and mice, that orforglipron is not pharmacologically active in rats or mice and did not produce tumors in rodents, and that because orforglipron is active at the human GLP-1 receptor the human relevance of those rodent findings has not been determined. The product is contraindicated in people with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia syndrome type 2, and in people with known serious hypersensitivity to orforglipron or to any of the excipients in the product. The label's warnings and precautions cover acute pancreatitis, severe gastrointestinal reactions, acute kidney injury from volume depletion, hypoglycemia, serious hypersensitivity reactions, diabetic retinopathy complications in people with type 2 diabetes, acute gallbladder disease, and pulmonary aspiration during general anesthesia and deep sedation. On hypoglycemia the label states that the product lowers blood glucose and can cause hypoglycemia, that hypoglycemia has also been associated with it in adults without type 2 diabetes, and that combining it with insulin or an insulin secretagogue may increase the risk, including severe hypoglycemia. The most common adverse reactions, reported in at least 5% of treated patients, are nausea, constipation, diarrhea, vomiting, dyspepsia, abdominal pain, headache, abdominal distension, fatigue, eructation, gastroesophageal reflux disease, flatulence and hair loss. The label also states that weight loss offers no benefit during pregnancy and may cause fetal harm.^[2]

• A label lists warnings and reactions that the agency requires to be communicated. It does not give the frequency of each warned-about event, and the listed warnings are not evidence that each event was caused by the drug in any individual.
• The boxed warning is a class-based caution: the label itself states that orforglipron did not produce tumors in rodents and that the human relevance of the rodent finding is undetermined. It is neither evidence that the drug causes thyroid tumors in people nor evidence that it does not.
• The adverse-reaction list is drawn from the label's placebo-controlled trial pool. Rates for individual reactions were not extracted here, and postmarketing reports carry no denominator.
• This describes the approved product. It is not a safety statement about any unapproved or compounded material sold under the same name.

Gastrointestinal effects were the most common adverse events in both phase 3 trials, and were described as mostly mild to moderate. In the 72-week obesity trial, adverse events led to treatment discontinuation in 5.3% to 10.3% of participants across the orforglipron groups, compared with 2.7% of those receiving placebo. In the 40-week type 2 diabetes trial, permanent discontinuation because of adverse events occurred in 4.4% to 7.8% of participants receiving orforglipron and in 1.4% of those receiving placebo, and most gastrointestinal events occurred during dose escalation. Independently of these trials, the approval letter records two separate agency actions about possible drug-induced liver injury. One is an obligation: a required postmarketing trial under which the sponsor must complete an ongoing active-controlled trial and submit an assessment of potential drug-induced liver injury alongside adjudicated major adverse cardiovascular events. The other is a request rather than a requirement, that for five years after approval the sponsor report and analyse cases of possible drug-induced liver injury through expedited and periodic safety reporting.^[4][5][3]

• Two of the three sources were inspected as abstracts, so the adverse-event tables and their denominators were not read. Discontinuation percentages are reported as ranges across dose groups without per-group counts.
• A required postmarketing trial and a requested pharmacovigilance programme are both instructions to collect and analyse data. Neither is a finding that the drug causes liver injury, and no such finding was inspected.
• Trial adverse-event reporting describes what happened to participants under trial conditions. It does not establish causation for any individual event or an incidence rate outside those trials.

In ATTAIN-1, a phase 3 trial in which 3,127 adults with obesity and without diabetes were randomized to one of three daily doses of orforglipron or placebo for 72 weeks, the mean change in body weight from baseline to week 72 was -7.5% (95% confidence interval -8.2 to -6.8), -8.4% (-9.1 to -7.7) and -11.2% (-12.0 to -10.4) across the three orforglipron groups, compared with -2.1% (-2.8 to -1.4) with placebo. In the highest-dose group, 54.6% of patients lost at least 10% of body weight, 36.0% lost at least 15% and 18.4% lost at least 20%, compared with 12.9%, 5.9% and 2.8% respectively with placebo. The abstract also reports improvement in waist circumference, systolic blood pressure, triglyceride levels and non-HDL cholesterol compared with placebo.^[4]

• Abstract-only inspection: the tables, supplementary appendix and protocol were not read, and the abstract gives no per-group participant counts.
• The cardiometabolic improvements are reported in the abstract as significant relative to placebo without effect sizes, so their magnitude cannot be stated here.
• These are 72-week results in adults with obesity and without diabetes, in a trial funded by the manufacturer. They do not describe longer treatment, other populations or clinical outcomes such as cardiovascular events.
• Doses appear here only because they identify the randomized groups whose results are reported. They describe the trial, not a recommendation.

ACHIEVE-1 studied orforglipron in a condition for which it is not approved. In this phase 3 trial, 559 adults with type 2 diabetes managed by diet and exercise alone were randomized to one of three daily doses or placebo for 40 weeks. Mean baseline glycated hemoglobin was 8.0%. At week 40 the estimated mean change from baseline was -1.24, -1.47 and -1.48 percentage points across the three orforglipron groups, compared with -0.41 percentage points with placebo; the estimated differences from placebo were -0.83 (95% confidence interval -1.10 to -0.56), -1.06 (-1.33 to -0.79) and -1.07 (-1.33 to -0.81) percentage points. Body weight changed by -4.5%, -5.8% and -7.6% across the orforglipron groups and by -1.7% with placebo. The abstract reports no episodes of severe hypoglycemia.^[5]

• Type 2 diabetes is not an approved indication for this product in the United States. These trial results describe what was measured in a trial and are not a statement about approved use.
• Abstract-only inspection: tables, supplementary appendix and protocol were not read, and no per-group participant counts are given.
• Participants were treated with diet and exercise alone at entry, so this does not describe people already taking other glucose-lowering medicines.
• Forty weeks of glycated-hemoglobin change is a laboratory measure. It is not a measure of diabetes complications, cardiovascular events or survival.

An earlier randomized, double-blind trial that its own abstract describes as phase 2 enrolled 272 adults with obesity, or with overweight plus at least one weight-related coexisting condition and without diabetes, and compared four daily doses of orforglipron with placebo over 36 weeks. Mean baseline body weight was 108.7 kg. At week 26, the primary end point, mean change in body weight ranged from -8.6% to -12.6% across the orforglipron dose cohorts and was -2.0% with placebo; at week 36 the range was -9.4% to -14.7% with orforglipron and -2.3% with placebo. A reduction of at least 10% by week 36 occurred in 46% to 75% of participants across the orforglipron cohorts, compared with 9% of those receiving placebo.^[6]

• This is dose-finding development context, not confirmatory evidence. The later phase 3 obesity trial is the larger and longer study and is recorded separately.
• The trial's own abstract calls it a phase 2 trial while PubMed indexes it as Clinical Trial, Phase I. The discrepancy is recorded rather than resolved; the protocol was not inspected.
• Abstract-only inspection, with results given as ranges across dose cohorts and no per-cohort participant counts, so the denominators cannot be checked.
• Doses appear here only because they identify the randomized cohorts whose results are reported.

The approved United States label records interactions in both directions. Table 2 states that CYP3A4 inhibitors increase orforglipron exposure, which may increase the risk of adverse reactions, and that strong CYP3A4 inhibitors which also clinically inhibit OATP1B are expected to increase plasma concentrations significantly; the label directs prescribers to avoid using the product together with strong CYP3A4 inhibitors of that kind, naming ritonavir as an example, and sets a ceiling on use with other strong CYP3A4 inhibitors. The same table states that induction of CYP3A4 decreases orforglipron exposure and may reduce its effectiveness, that strong CYP3A4 inducers should be avoided, and that effectiveness should be monitored with moderate inducers. Table 3 states that taking the product with simvastatin increased exposure to the active metabolite simvastatin acid two-fold, which the label says could be clinically meaningful at the highest simvastatin dose, and that because the drug stimulates insulin release when blood glucose is elevated it could increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue such as a sulfonylurea. Section 7.3 states that the drug delays gastric emptying and so may affect the absorption of other medicines taken by mouth, and advises people using oral hormonal contraceptives to switch to a non-oral method or add a barrier method around the start of treatment and after each dose increase.^[2]

• These are label statements about the approved product. The label does not report the studies behind each entry in these tables, so the size, design and population of the supporting pharmacokinetic work were not inspected here.
• An exposure change is not the same as a clinical harm. Only the simvastatin entry carries a numerical exposure change, and the label itself qualifies when that change might matter.
• The hypoglycemia entry describes a class mechanism for GLP-1 receptor agonists combined with insulin or insulin secretagogues. It is not a measured event rate for any particular combination.
• This reference records what the label says an interaction is and does. It does not reproduce the label's dosage instructions, which are directions to a prescriber rather than educational content.