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Orforglipron
GLP-1 Analogs

Orforglipron

Foundayo (Eli Lilly)

Orforglipron (LY3502970) is a small-molecule, non-peptide GLP-1 receptor agonist taken as a tablet once a day. Unlike oral semaglutide (Rybelsus), which is a peptide that needs an absorption enhancer and a fasting window, orforglipron is a small molecule: the US label says to take it once daily with or without food, and its absolute oral bioavailability was about 77% after a 0.8 mg dose. Regulatory status: the FDA approved orforglipron as FOUNDAYO on April 1, 2026 (NDA 220934), as an adjunct to a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity, or with overweight plus at least one weight-related condition. It was the first new molecular entity approved under the FDA's Commissioner's National Priority Voucher pilot. The US label carries a boxed warning about thyroid C-cell tumors and is contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. In the UK, the MHRA authorised it on August 10, 2026 for weight management and for glycaemic control in insufficiently controlled type 2 diabetes, as a prescription-only medicine. In the US it is not approved for type 2 diabetes as of the current label. Evidence: in the phase 3 ATTAIN-1 trial (3,127 adults with obesity, no diabetes, 72 weeks), mean weight change was -7.5%, -8.4% and -11.2% with the 6, 12 and 36 mg investigational doses versus -2.1% with placebo; in ATTAIN-2 (adults with obesity and type 2 diabetes) it was -5.1% to -9.6% versus -2.5%. The label expresses these as the equivalent tablet doses of 5.5, 9 and 17.2 mg. In type 2 diabetes, ACHIEVE-1 lowered HbA1c by 1.24 to 1.48 percentage points versus 0.41 with placebo over 40 weeks, ACHIEVE-3 showed superiority over oral semaglutide for HbA1c at 52 weeks, and ACHIEVE-4 showed cardiovascular non-inferiority to insulin glargine. Gastrointestinal adverse events (nausea, constipation, diarrhea, vomiting) were the most common and mostly occurred during dose escalation. Approved GLP-1 therapies with long track records, including injectable semaglutide and tirzepatide, remain standard options; orforglipron should only be used under a prescriber's supervision.

Specifications

Origin / ManufacturerSynthetic small molecule
Regulatory Status
FDA-approved (FOUNDAYO, chronic weight management, 2026)MHRA-authorised (UK, 2026)
Active Components
Orforglipron (LY3502970)
StorageRoom temperature, 20–25°C (68–77°F); excursions 15–30°C permitted (US label)
Shelf LifeSee product packaging
Form FactorOral tablet, once daily (0.8, 2.5, 5.5, 9, 14.5 and 17.2 mg)

Clinical Evidence

Phase 2 (obesity, no diabetes, n=272, 36 weeks): mean weight change -9.4% to -14.7% across 12–45 mg doses versus -2.3% with placebo; gastrointestinal events led to discontinuation in 10–17% of participants across dose cohorts.

Clinical report reference

Phase 2 (type 2 diabetes, n=383, 26 weeks): HbA1c fell by up to 2.10% (1.67% placebo-adjusted) versus 0.43% with placebo and 1.10% with dulaglutide 1.5 mg; body weight fell by up to 10.1 kg.

Clinical report reference

ATTAIN-1 (phase 3, n=3,127, obesity without diabetes, 72 weeks): -7.5% (6 mg), -8.4% (12 mg) and -11.2% (36 mg) versus -2.1% with placebo; adverse events caused discontinuation in 5.3–10.3% versus 2.7% with placebo.

Clinical report reference

ATTAIN-2 (phase 3, n=1,613, obesity with type 2 diabetes, 72 weeks): -5.1%, -7.0% and -9.6% with 6, 12 and 36 mg versus -2.5% with placebo.

Clinical report reference

ACHIEVE-1 (phase 3, early type 2 diabetes, n=559, 40 weeks): HbA1c -1.24 to -1.48 percentage points versus -0.41 with placebo; no severe hypoglycemia.

Clinical report reference

ACHIEVE-3 (phase 3, n=1,698, 52 weeks, open label): orforglipron 12 and 36 mg were non-inferior and superior to oral semaglutide 7 and 14 mg on HbA1c, but GI events, discontinuations for adverse events and pulse-rate increase were higher with orforglipron.

Clinical report reference

ACHIEVE-4 (phase 3, n=2,749, type 2 diabetes with high cardiovascular risk, median 2 years): MACE-4 occurred in 4.2% with orforglipron versus 5.0% with insulin glargine (HR 0.84; non-inferiority met).

Clinical report reference

ATTAIN-MAINTAIN (phase 3b): after switching from tirzepatide or semaglutide, participants on orforglipron kept about 75–79% of their prior weight reduction at 52 weeks versus 38–49% on placebo.

Clinical report reference

Frequently Asked Questions

Sources & References

Every clinical claim on this page traces to a primary peer-reviewed source.

  1. 1Wharton S, Blevins T, Connery L, et al.. Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. New England Journal of Medicine. 2023;389(10):877-888. doi:10.1056/NEJMoa2302392 PMID:37351564
  2. 2Frias JP, Hsia S, Eyde S, et al.. Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study. Lancet. 2023;402(10400):472-483. doi:10.1016/S0140-6736(23)01302-8 PMID:37369232
  3. 3Wharton S, Aronne LJ, Stefanski A, et al.. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. New England Journal of Medicine. 2025;393(18):1796-1806. doi:10.1056/NEJMoa2511774 PMID:40960239
  4. 4Horn DB, Ryan DH, Kis SG, et al.. Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. Lancet. 2026;406(10522):2927-2944. doi:10.1016/S0140-6736(25)02165-8 PMID:41275875
  5. 5Rosenstock J, Hsia S, Nevarez Ruiz L, et al.. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes. New England Journal of Medicine. 2025;393(11):1065-1076. doi:10.1056/NEJMoa2505669 PMID:40544435
  6. 6Rosenstock J, Yabe D, Cox D, et al.. Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial. Lancet. 2026;407(10534):1147-1160. doi:10.1016/S0140-6736(26)00202-3 PMID:41765029
  7. 7Klein KR, Wysham C, Tuttle 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. Lancet. 2026. doi:10.1016/S0140-6736(26)01865-9 PMID:42815506
  8. 8Aronne LJ, Horn DB, le Roux CW, et al.. Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. Nature Medicine. 2026;32(7):2679-2687. doi:10.1038/s41591-026-04386-7 PMID:42120723
  9. 9Pratt E, Ma X, Liu R, et al.. Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1a, blinded, placebo-controlled, randomized, single- and multiple-ascending-dose study in healthy participants. Diabetes, Obesity and Metabolism. 2023;25(9):2634-2641. doi:10.1111/dom.15184 PMID:37344954
  10. 10U.S. Food and Drug Administration. FOUNDAYO (orforglipron) tablets, for oral use: Prescribing Information (NDA 220934, revised 07/2026). U.S. Food and Drug Administration. 2026.
  11. 11U.S. Food and Drug Administration. FDA Approves First New Molecular Entity Under National Priority Voucher Program. U.S. Food and Drug Administration. 2026.
  12. 12Medicines and Healthcare products Regulatory Agency. UK first in Europe to authorise orforglipron for weight management and type 2 diabetes. Medicines and Healthcare products Regulatory Agency (GOV.UK). 2026.

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Editorial Team

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