Orforglipron (LY3502970)
Eli Lilly’s once-daily, small-molecule ORAL GLP-1 receptor agonist (Foundayo, FDA-approved Apr 2026). Not a peptide – an oral alternative to injectable GLP-1 RAs (semaglutide, liraglutide) for chronic weight management.
WHAT IS ORFORGLIPRON (LY3502970)?
Detailed overview
Orforglipron (LY3502970) is Eli Lilly’s once-daily, small-molecule oral GLP-1 receptor agonist, FDA-approved on 1 April 2026 as Foundayo for chronic weight management (obesity, or overweight with at least one weight-related comorbidity, alongside diet and exercise). Structurally it is not a peptide – a small organic molecule that activates the GLP-1 receptor, so it resists gastric digestion and is taken once daily without food or water restrictions. The Phase 3 ATTAIN-1 trial (Wharton 2025 NEJM) showed ~12.4% body-weight reduction at 72 weeks in the highest-dose group versus ~0.9% for placebo (3,127 participants without diabetes). Oral bioavailability is ~77% and the long half-life (~29-49 h) allows once-daily dosing. A type-2-diabetes indication (ACHIEVE program) and EU authorisation are still in progress.
ATC code
None yet (not in the WHO ATC index)
Prescription
Prescription only (Rx), FDA 2026 (Foundayo)
Mechanism
Oral small-molecule GLP-1 receptor agonist
Half-life
29-49 h (once-daily dosing)
Onset
Tmax 4-8 h; full weight effect over months
Data console
Lab data
Safety
Side effects, stop signs, contraindications
Side effects · 7
- Gastrointestinal effects (nausea, vomiting, diarrhea, abdominal discomfort), especially during dose titration; these are dose-dependent and the most common adverse events, though with somewhat lower incidence than injectable peptide GLP-1 RAs.
- Decreased appetite and early satiety with associated weight loss; this is partly mechanism-related but can also lead to unwanted degree of weight and lean-mass loss.
- Risk of hypoglycemia when combined with insulin or a sulfonylurea (on its own the GLP-1 RA glucose-dependent action makes hypoglycemia risk low).
- Headache, fatigue, and dizziness in the early phase of treatment.
- Acute pancreatitis is a rare but potentially serious risk, as with GLP-1 receptor agonists generally; persistent, severe abdominal pain radiating to the back requires immediate medical evaluation.
- Gallbladder disease (gallstones, acute cholecystitis), which may be related both to rapid weight loss and to the GLP-1 effect.
- Marked fullness, reflux, and occasionally altered absorption of orally taken medicines due to slowed gastric emptying.
Contraindications · 3
- History of medullary thyroid carcinoma (MEN-2 syndrome) – class effect for all GLP-1 RAs
- History of pancreatitis (relative)
- Severe gastroparesis
Studies
Related research and clinical findings
Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment.
Wharton S, Aronne LJ, Stefanski A
Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study.
Frías JP, Hsia S, Eyde S, Liu R, Ma X, Konig M, Kazda C, Mather KJ, Haupt A, Pratt E, Dunn J, Robins D, Karanikas C, Thomas MK
Small-Molecule Oral Versus Injectable Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists: Comparative Efficacy, Safety, and Cost.
Patel D
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Educational drug info from official sources (PubMed, FDA, EMA). Does NOT replace medical consultation or the SmPC. Talk to your doctor!
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The information here is for educational and scientific purposes only. Medication use requires medical consultation and a prescription. The indications, dose ranges, and side effects listed here do NOT replace the official Summary of Product Characteristics (SmPC) or consultation with a physician. Do not start or stop any medication on your own. In an emergency, call your local emergency number.