Mechanism
How Orforglipron Works: Small Molecule GLP-1 Explained
Why a pill that mimics GLP-1 is such a pharmaceutical breakthrough — and how it survives the digestive system.
Orforglipron is Eli Lilly's once-daily oral GLP-1 pill — no injections, no food restrictions, no refrigeration. The NDA is submitted. FDA approval could be weeks away.
Orforglipron (code name LY3502970) is an investigational once-daily oral medication developed by Eli Lilly and Company. It is a small-molecule, non-peptide GLP-1 receptor agonist — meaning it mimics the GLP-1 hormone to suppress appetite and improve blood sugar, but in a form that can survive the digestive system and be taken as a simple pill.
This is the key breakthrough: existing injectable GLP-1 drugs (like Ozempic and Wegovy) are peptide-based and would be destroyed by stomach acid if swallowed. Orforglipron's unique chemical structure bypasses this problem entirely — and critically, it requires no food or water restrictions, unlike existing oral semaglutide (Rybelsus).
Eli Lilly has submitted a New Drug Application (NDA) to the FDA and received a Commissioner's National Priority Review Voucher, which could compress the review timeline to weeks rather than months.
Read Full Overview →Small-molecule oral GLP-1 receptor agonist (non-peptide)
Eli Lilly (licensed from Chugai Pharmaceutical, 2018)
NDA submitted · Priority Review Voucher granted · Decision expected 2026
Estimated 25–30% of people with obesity avoid GLP-1 therapy due to needle phobia. A daily pill removes this barrier entirely.
Unlike oral semaglutide (Rybelsus), orforglipron can be taken at any time of day with or without food — no 30-minute fasting window required.
Injectable GLP-1 drugs require cold storage. A stable oral pill dramatically improves access in rural areas and lower-income countries.
Under agreements with the US government, orforglipron's starting dose is expected to be priced at $149/month upon approval — well below injectable alternatives.
Small-molecule pills are far cheaper and easier to manufacture at scale than peptide injectables, with huge implications for global access.
ATTAIN-MAINTAIN trial showed orforglipron can maintain weight loss after stopping injectable Wegovy or Zepbound — a first-of-its-kind finding.
Eli Lilly licenses worldwide development and commercialization rights for orforglipron from Chugai Pharmaceutical Co., Ltd., a Roche subsidiary based in Japan.
Phase 2 data demonstrated meaningful weight loss in adults with obesity and type 2 diabetes, validating the oral small-molecule approach and triggering Phase 3 investment.
ATTAIN-1 results published in the New England Journal of Medicine showed 12.4% weight loss at the highest dose over 72 weeks in 3,127 participants. ATTAIN-2 confirmed results in type 2 diabetes.
Eli Lilly submits NDA to the FDA for obesity indication. Orforglipron is granted the FDA Commissioner's National Priority Review Voucher — the first drug selected for this new program — dramatically accelerating the review timeline.
With the Priority Voucher, FDA review could be completed in weeks to months rather than the standard 6–10 months. Approval and commercial launch could follow quickly, with a starting dose priced at $149/month.
Oral pill vs. the world's most prescribed GLP-1 injection. How close is the weight loss gap?
Read comparison →Daily pill vs. weekly dual-agonist injection — convenience vs. maximum weight loss.
Read comparison →Oral convenience vs. injectable triple agonist — two very different approaches from the same company.
Read comparison →Every approved and investigational weight loss drug side by side in one complete 2026 table.
See full table →Why a pill that mimics GLP-1 is such a pharmaceutical breakthrough — and how it survives the digestive system.
What adverse events were reported across 4,500+ trial participants, and how they compare to injectable GLP-1 drugs.
When will it be available? Who qualifies? What will it cost? How does it compare to injections? All your questions answered.