# Orforglipron > The first small-molecule (non-peptide) GLP-1 receptor agonist to reach approval — a once-daily pill with no food or water restrictions, FDA-approved as Foundayo for chronic weight management in April 2026. - Also known as: Foundayo, LY3502970, OWL833 - Class: Metabolic - FDA approved: Yes - Canonical page: https://americanpeptide.com/catalog/orforglipron ## Overview Orforglipron is not a peptide. It is a small organic molecule (~883 Da) that activates the same GLP-1 receptor as semaglutide, which is why it belongs in this reference: it is the non-peptide answer to the problems peptides create — injection, cold chain, and complex synthesis. Discovered by Chugai and developed by Eli Lilly, it is taken once daily by mouth without the fasting rules oral semaglutide requires. The FDA approved it as Foundayo for chronic weight management on April 1, 2026, on Phase 3 ATTAIN-1 data showing 12.4% mean weight reduction at 72 weeks on the highest dose versus 0.9% on placebo. Every other GLP-1 agonist in this catalog is a peptide — a chain of amino acids that the gut digests, which is why they are injected (or, for oral semaglutide, co-formulated with an absorption enhancer and taken fasting with a sip of water). Orforglipron takes a different route entirely: it is a conventional small molecule, made by organic synthesis rather than peptide synthesis, that happens to switch on the GLP-1 receptor. It survives digestion, is absorbed like an ordinary tablet, and has a half-life of roughly 29–49 hours, supporting once-daily dosing at any time of day. It was discovered at Chugai Pharmaceutical (as OWL833) and licensed to Eli Lilly in 2018. The Phase 3 program ran on two tracks. ATTAIN-1 (Wharton et al., NEJM 2025) randomized 3,127 adults with obesity or overweight and reported mean weight change at 72 weeks of −12.4% on the 36 mg dose versus −0.9% on placebo. ACHIEVE-1 (Rosenstock et al., NEJM 2025), in early type 2 diabetes, reported HbA1c reductions of 1.3–1.6 percentage points at 40 weeks. Those weight figures are below injectable semaglutide 2.4 mg and well below tirzepatide — the case for orforglipron is convenience and manufacturing scale, not peak efficacy. The FDA approved orforglipron as Foundayo on April 1, 2026 for chronic weight management in adults with obesity, or overweight with a weight-related condition — the first new molecular entity cleared under the Commissioner’s National Priority Voucher pilot, after an unusually short review. The label carries the class boxed warning about thyroid C-cell tumors. A type 2 diabetes indication was being pursued separately on the ACHIEVE program; check the current label before relying on its status. ## Mechanism Non-peptide agonist of the GLP-1 receptor that binds within the transmembrane domain rather than at the peptide-binding site. Signaling is biased toward G-protein / cAMP activation with little β-arrestin recruitment. Downstream effects match the class: glucose-dependent insulin secretion, slowed gastric emptying, reduced appetite. ## Chemistry | Property | Value | | --- | --- | | Molecular formula | C48H48F2N10O5 | | Molecular weight | 883 Da | | CAS number | 2212020-52-3 | | PubChem CID | [137319706](https://pubchem.ncbi.nlm.nih.gov/compound/137319706) | ## Research areas Studied in: Obesity, Type 2 diabetes, Oral incretin therapy, Weight maintenance. Guides on this site: - [Weight Loss & Metabolic Health](https://americanpeptide.com/research-areas/weight-loss): Incretin and metabolic peptides studied for glycemic control and fat loss. ## Key research - Non-peptide GLP-1 agonism — a small molecule that activates the GLP-1 receptor from within the transmembrane domain, with G-protein-biased signaling. - ATTAIN-1 (NEJM 2025, n=3,127, 72 weeks) — −12.4% mean weight change at 36 mg versus −0.9% placebo; basis for the obesity approval. - ACHIEVE-1 (NEJM 2025, 40 weeks) — HbA1c reduced by 1.3–1.6 percentage points in early type 2 diabetes versus ~0.1 on placebo. - Oral without restrictions — once daily, no fasting or water rules; unlike oral semaglutide, which needs the SNAC absorption enhancer and an empty stomach. - Regulatory — FDA-approved as Foundayo on April 1, 2026 for chronic weight management, under the National Priority Voucher pilot. ## Storage, handling & synthesis **Storage.** An oral tablet stored at controlled room temperature in its original packaging — no refrigeration or reconstitution, unlike the injectable peptide agonists. **Handling.** Not a lyophilized peptide: there is no vial, diluent, or reconstitution step. As a reference standard it is handled as a conventional small-molecule solid, protected from moisture. ## FAQs ### What is orforglipron? Orforglipron (Foundayo) is a once-daily oral GLP-1 receptor agonist from Eli Lilly. Unlike semaglutide or tirzepatide it is a small molecule, not a peptide. The FDA approved it for chronic weight management in April 2026. ### Is orforglipron a peptide? No. It is a small organic molecule (C48H48F2N10O5, about 883 Da) that activates the GLP-1 receptor. It is included in this peptide reference because it is the direct non-peptide counterpart to the GLP-1 peptides — same receptor, entirely different chemistry. ### How much weight do people lose on orforglipron? In ATTAIN-1 (NEJM 2025), adults on the highest dose lost a mean of 12.4% of body weight at 72 weeks versus 0.9% on placebo. That is less than injectable semaglutide 2.4 mg (~14.9% in STEP-1) or tirzepatide (~22.5% in SURMOUNT-1); the trials were not head-to-head. Population means, not individual predictions. ### How is it different from oral semaglutide (Rybelsus)? Oral semaglutide is a peptide co-formulated with the absorption enhancer SNAC and must be taken on an empty stomach with a small amount of water. Orforglipron is a small molecule absorbed like an ordinary tablet, with no food or water restrictions. ### What are the side effects of orforglipron? The same pattern as the injectable class — nausea, vomiting, diarrhea and constipation, mostly during dose escalation. The label carries the class boxed warning about thyroid C-cell tumors seen in rodents and advises against combining it with other GLP-1 therapies. This page is a research reference, not medical advice. ### Why does a small-molecule GLP-1 matter? Peptide GLP-1 drugs need long solid-phase or recombinant synthesis, fatty-acid acylation, sterile injectable manufacturing and cold storage. A small molecule is made by conventional chemical synthesis and pressed into room-temperature tablets — far easier to scale. ## Latest research Recent trials and publications mentioning Orforglipron, pulled automatically from ClinicalTrials.gov and PubMed (unfiltered search results, refreshed daily). ### Recent trials - [A Study of Orforglipron in Participants With Overweight at Risk of Development of Obesity-Related Complications or Progression to Class 1 Obesity](https://clinicaltrials.gov/study/NCT07794579) — RECRUITING · PHASE3 · NCT07794579 - [A Study of Orforglipron (LY3502970) Compared With Dulaglutide in Pediatric Participants With Type 2 Diabetes](https://clinicaltrials.gov/study/NCT07668336) — RECRUITING · PHASE3 · NCT07668336 - [A Platform Trial for Pediatric Participants With Obesity or Overweight (LY900040)](https://clinicaltrials.gov/study/NCT06672549) — RECRUITING · PHASE3 · NCT06672549 - [A Study of Orforglipron (LY3502970) on Cardiovascular Outcomes in Adults With Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease (ATTAIN-Outcomes)](https://clinicaltrials.gov/study/NCT07241390) — RECRUITING · PHASE3 · NCT07241390 - [Efficacy and Safety of Orforglipron in Participants With Peripheral Artery Disease](https://clinicaltrials.gov/study/NCT07223593) — RECRUITING · PHASE3 · NCT07223593 - [A Study of Orforglipron in Female Participants With Stress Urinary Incontinence Who Have Obesity or Overweight](https://clinicaltrials.gov/study/NCT07202884) — RECRUITING · PHASE3 · NCT07202884 --- Source: AmericanPeptide.com — https://americanpeptide.com/catalog/orforglipron Data license: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Attribution: AmericanPeptide.com. Research reference only — computational and educational content, not medical advice.