{"id":"orforglipron","name":"Orforglipron","aliases":["Foundayo","LY3502970","oral GLP-1","small-molecule GLP-1 receptor agonist"],"url":"https://lyoresearch.com/compounds/orforglipron","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Orforglipron (Foundayo) is a once-daily tablet that activates the GLP-1 receptor. It is not a peptide — it is a small molecule, which is why it survives digestion and needs no injection, refrigeration or food restriction. Its phase 3 programme is published: about 11% average weight loss over 72 weeks in obesity, and HbA1c reductions of roughly 1.5 points in early type 2 diabetes. The FDA approved it for weight management on 1 April 2026. The effect is smaller than injected tirzepatide or semaglutide; the delivery is far easier.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"Phase 3 programme published","regulatory_status":"Approved (Rx) — United States","molecule":{"formula":"C48H48F2N10O5","molecular_weight":"883.0","cas":"2212020-52-3","pubchem_cid":137319706,"note":null},"pharmacokinetics":{"basis":"label","route":"Oral tablet, once daily","half_life":"About 29-49 hours","licensed_regimen":"0.8 mg daily, then after ≥30 days 2.5 mg, then 5.5 mg, then 9, 14.5 or 17.2 mg daily with ≥30 days between escalations; maximum 17.2 mg daily","product":"Foundayo","source":{"title":"Foundayo prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8ac446c5-feba-474f-a103-23facb9b5c62"}},"outcomes":[{"outcome":"Body weight","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"Phase 3 RCT (n=3,127) + programme","evidence":"ATTAIN-1, 72 weeks in adults with obesity and no diabetes: −11.2% on the 36 mg dose versus −2.1% on placebo. 36.0% lost at least 15% of body weight, against 5.9% on placebo.","references":[{"citation":"Wharton S, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1).","where":"N Engl J Med, 2025;393:1796–1806","url":"https://pubmed.ncbi.nlm.nih.gov/40960239/"}],"verbatim":{"text":"The mean change in body weight from baseline to week 72 was -7.5% (95% confidence interval [CI], -8.2 to -6.8) with 6 mg of orforglipron, -8.4% (95% CI, -9.1 to -7.7) with 12 mg of orforglipron, and -11.2% (95% CI, -12.0 to -10.4) with 36 mg of orforglipron, as compared with -2.1% (95% CI, -2.8 to -1.4) with placebo (P<0.001 for all comparisons with placebo).","citation":"Wharton S, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1).","url":"https://pubmed.ncbi.nlm.nih.gov/40960239/"}},{"outcome":"Blood glucose (HbA1c)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Phase 3 RCT (n=559) + programme","evidence":"ACHIEVE-1, 40 weeks in type 2 diabetes managed by diet and exercise alone: HbA1c fell 1.24–1.48 points versus 0.41 on placebo, bringing the average to 6.5–6.7%.","references":[{"citation":"Rosenstock J, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist, in early type 2 diabetes (ACHIEVE-1).","where":"N Engl J Med, 2025;393:1065–1076","url":"https://pubmed.ncbi.nlm.nih.gov/40544435/"}],"verbatim":{"text":"At week 40, the estimated mean change from baseline in the glycated hemoglobin level was -1.24 percentage points with the 3-mg dose, -1.47 percentage points with the 12-mg dose, -1.48 percentage points with the 36-mg dose, and -0.41 percentage points with placebo.","citation":"Rosenstock J, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist, in early type 2 diabetes (ACHIEVE-1).","url":"https://pubmed.ncbi.nlm.nih.gov/40544435/"}},{"outcome":"Major cardiovascular events","grade":"B","grade_meaning":"probable, not settled","effect_size":"not measurable","adverse":false,"human_studies":"1 phase 3 safety RCT (ACHIEVE-4, n=2,749, median 2 yr)","evidence":"ACHIEVE-4, published in The Lancet on 30 September 2026: adults with type 2 diabetes, overweight or obesity and established cardiovascular or chronic kidney disease took orforglipron or insulin glargine, open label. A major cardiovascular event occurred in 4.2% on orforglipron and 5.0% on glargine (hazard ratio 0.84, 95% CI 0.59–1.20). That meets non-inferiority, so cardiovascular safety is confirmed; the interval crosses 1, so a reduction in events is not shown. Deaths were 1.4% against 3.2%, in a trial built to test safety, not that difference. Clinically significant hypoglycaemia: 6.8% vs 19.2%.","references":[{"citation":"Klein KR, et al. Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial.","where":"Lancet, 2026 (online 30 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42815506/"}],"verbatim":{"text":"Over a median follow-up of 2 years, the primary outcome occurred in 57 (4·2%) of 1358 orforglipron participants and 67 (5·0%) of 1343 insulin glargine participants, showing non-inferiority to insulin glargine for MACE-4 (HR 0·84; 95% CI 0·59-1·20; p<0·0001 for non-inferiority).","citation":"Klein KR, et al. Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial.","url":"https://pubmed.ncbi.nlm.nih.gov/42815506/"}},{"outcome":"GI side effects","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":true,"human_studies":"Phase 3 programme","evidence":"The familiar incretin profile. In ATTAIN-1, adverse events caused 5.3–10.3% of participants to stop, against 2.7% on placebo. In ACHIEVE-4, gastrointestinal events were reported in 62.1% on orforglipron against 14.2% on insulin glargine.","references":[{"citation":"Wharton S, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1).","where":"N Engl J Med, 2025;393:1796–1806","url":"https://pubmed.ncbi.nlm.nih.gov/40960239/"},{"citation":"Klein KR, et al. Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial.","where":"Lancet, 2026 (online 30 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42815506/"}],"verbatim":{"text":"The most common adverse events with orforglipron were gastrointestinal effects, which were mostly mild to moderate.","citation":"Wharton S, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1).","url":"https://pubmed.ncbi.nlm.nih.gov/40960239/"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"No EMA marketing authorisation. Under regulatory review following the phase 3 programme."},{"region":"United States","status":"Approved, prescription-only","note":"Foundayo approved by the FDA on 1 April 2026 to reduce excess body weight and maintain weight reduction in adults with obesity, or with overweight and at least one weight-related condition. Anything sold as orforglipron without a prescription is not the licensed product."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence."},{"region":"Australia","status":"Not on the ARTG","note":"Investigational only."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Not prohibited","note":"GLP-1 receptor agonists are not on the 2026 Prohibited List."}],"faq":[{"q":"Is orforglipron as good as Ozempic or Mounjaro?","a":"For weight, no. About 11% average loss at 72 weeks compares with roughly 15% for semaglutide and 21% for tirzepatide in their own trials. Cross-trial comparison is unreliable, but the gap is consistent. The trade is that it is a daily tablet with no injection and no food timing."},{"q":"Is orforglipron a peptide?","a":"No. It is a small synthetic molecule that happens to hit the same receptor. That is precisely why it works as a pill."},{"q":"Can I buy it?","a":"In the United States it is a prescription medicine: the FDA approved it as Foundayo on 1 April 2026 for weight management. LYO has not verified an approval in the other regions on this page. Products sold under the name without a prescription are not the licensed drug."}],"references":[{"cite":"Wharton S, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1).","where":"N Engl J Med, 2025;393:1796–1806","url":"https://pubmed.ncbi.nlm.nih.gov/40960239/","note":"3,127 adults, 72 weeks."},{"cite":"Rosenstock J, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist, in early type 2 diabetes (ACHIEVE-1).","where":"N Engl J Med, 2025;393:1065–1076","url":"https://pubmed.ncbi.nlm.nih.gov/40544435/","note":"559 participants, 40 weeks."},{"cite":"Horn DB, et al. Orforglipron for obesity in people with type 2 diabetes (ATTAIN-2): a phase 3 randomised trial.","where":"Lancet, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/41275875/"},{"cite":"Wharton S, et al. Hepatic safety of orforglipron: a pooled analysis of the phase 3 clinical trials.","where":"Diabetes Obes Metab, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42338042/"},{"cite":"Klein KR, et al. Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial.","where":"Lancet, 2026 (online 30 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42815506/","note":"2,749 randomised, 317 sites, median follow-up 2 years; MACE-4 hazard ratio 0.84 (95% CI 0.59–1.20), non-inferiority margin 1.8. NCT05803421."},{"cite":"FDA. Novel Drug Approvals for 2026 (Foundayo, orforglipron, approved 1 April 2026).","where":"FDA, read 7 Oct 2026","url":"https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2026","note":"Approved use on the approval date: chronic weight management in adults with obesity, or overweight with a weight-related condition."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"ACHIEVE-4 (Lancet, 30 Sep 2026) added as a cardiovascular row: safety confirmed against insulin glargine, no reduction in events shown, graded B at effect 0. Status corrected to approved in the United States (Foundayo, FDA, 1 April 2026), which this page had not yet recorded. Other grades unchanged."},{"date":"2026-09-03","note":"Initial publication from the published phase 3 programme (ATTAIN-1, ACHIEVE-1, ATTAIN-2)."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}