Orforglipron
Eli Lilly's once-daily ORAL non-peptide GLP-1 receptor agonist (LY3502970). The first oral small-molecule GLP-1 with no food/water restrictions (unlike Rybelsus). Phase 3 ACHIEVE program for diabetes and ATTAIN for obesity both ongoing.
Educational only — not medical advice. SmartPeptide does not prescribe, diagnose, or treat. Always consult a licensed healthcare provider before using any peptide, supplement, medication, or protocol.
What the research shows
Phase 2 obesity (n≈272, 36 weeks): ~14.7% mean body weight reduction at the highest dose vs. ~2.3% placebo. Phase 2 diabetes trials showed HbA1c reductions comparable to injectable GLP-1s. Phase 3 ACHIEVE + ATTAIN programs ongoing; expected approval read-out late 2025 / 2026.
What's still experimental
Phase 3 data + FDA approval pending. Long-term safety, durability, and direct head-to-head vs. semaglutide / tirzepatide unknown.
Anecdotal / community reports
Some forum interest, but Orforglipron is a small-molecule (not a peptide) and is harder to access via grey-market routes than peptide GLP-1s. Most discussion is anticipatory — 'when will it ship.'
Anecdotal reports are NOT scientific evidence. They reflect personal experience and may not generalize.
FDA approval status
Source: openFDA + DailyMed (NIH/NLM)- Full label on DailyMedFOUNDAYO(ORFORGLIPRON) · Eli Lilly and CompanyIndications & usage
1 INDICATIONS AND USAGE FOUNDAYO TM is indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition. FOUNDAYO™ is a GLP-1 receptor agonist indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition. ( 1 ) Limitations of Use Concomitant use with another GLP-1 receptor agonist is not recommended. ( 1 ) Limitations of Use Concomitant use with another GLP-1 receptor agonist is not re…
Dosage & administration2 DOSAGE AND ADMINISTRATION Take FOUNDAYO orally once daily, with or without food. ( 2.1 ) Swallow tablets whole. Do not break, crush, or chew. ( 2.1 ) Do not take more than one tablet per day. ( 2.1 ) Starting dosage is 0.8 mg once daily. After at least 30 days, increase dosage to 2.5 mg once daily. ( 2.1 ) After at least 30 days on the 2.5 mg dosage, increase dosage to 5.5 mg once daily. ( 2.1 ) Dosage may be increased to the next dosage level (9 mg, 14.5 mg, or 17.2 mg once daily) after at least 30 days on the current dosage, based on treatment response and tolerability. ( 2.1 ) Maximum dosage is 17.2 mg once daily. ( 2.1 ) 2.1 Recommended Dosage and Administration Recommended Administration Take FOUNDAYO orally once daily, with or without food. Swallow tablets whole. Do not break, crus…
Warnings5 WARNINGS AND PRECAUTIONS Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including FOUNDAYO. Discontinue if pancreatitis is suspected. ( 5.2 ) Severe Gastrointestinal Reactions: Use has been associated with gastrointestinal adverse reactions, sometimes severe. FOUNDAYO is not recommended in patients with severe gastroparesis. ( 5.3 ) Acute Kidney Injury Due to Volume Depletion: Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. ( 5.4 ) Hypoglycemia: Concomitant use with insulin or an insulin secretagogue may increase the risk of hypoglycemia, including severe hypoglycemia. Reducing the dosage of insulin or insulin secretagogue may be necessary. Inform all patients of the risk of hypoglycemia and educ…
All current FDA labels (DailyMed)
FDA enforcement & recalls
Live · openFDA Drug Enforcement APIMechanism & targets
ChEMBL · UniProt · Open TargetsMolecule (ChEMBL)
View on ChEMBLProtein targets (UniProt)
- Glucagon-like peptide 1 receptorP43220gene: GLP1RHomo sapiens· 463 aaReviewed
G-protein coupled receptor for glucagon-like peptide 1 (GLP-1) (PubMed:19861722, PubMed:26308095, PubMed:27196125, PubMed:28514449, PubMed:7517895, PubMed:8216285, PubMed:8405712). Ligand binding triggers activation of a signaling cascade that leads to the activation of adenylyl cyclase and increased intracellular cAMP levels (PubMed:19861722, PubMed:26308095, PubMed:27196125, PubMed:28514449, PubMed:7517895, PubMed:8216285, PubMed:8405712). Plays a role in regulating insulin secretion in respon…
Live research
PubMed · ClinicalTrials.gov · Europe PMC · OpenAlexClinical trials (ClinicalTrials.gov)
- A Study of Orforglipron (LY3502970) in Adolescent Participants With Obesity, or Overweight With Related ComorbiditiesRECRUITINGNCT06672939 · PHASE3 · n=150 · 2024-11-18
- A Study of LY3502970 in Participants With Type 2 Diabetes MellitusCOMPLETEDNCT05048719 · PHASE2 · n=383 · 2021-09-15
- A Study of LY3502970 in Chinese Participants With Obesity or Are Overweight With Weight-related ComorbiditiesCOMPLETEDNCT06023095 · PHASE1 · n=24 · 2023-09-21
- A Multiple-Dose Study of LY3502970 in Healthy ParticipantsCOMPLETEDNCT05110794 · PHASE1 · n=34 · 2021-11-05
- A Drug-Drug Interaction (DDI) Study of Orforglipron With Carbamazepine in Healthy ParticipantsCOMPLETEDNCT06370728 · PHASE1 · n=30 · 2024-05-06
Europe PMC — 350 additional records
Includes EU/UK studies and PubMed Central full-text articles. Often surfaces research weeks before PubMed indexes it.
- GLP-1 receptor agonists in stroke prevention: a narrative review on emerging therapeutic frontiersChikatimalla R, Shah A, Shah T, et al. · 2026Open access
- 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 trialHorn DB, Ryan DH, Kis SG, et al. · 2026· cited 3×
- Oral Semaglutide 25 mg Versus Orforglipron 36 mg in Obesity: A Population-Adjusted Indirect Treatment ComparisonMichalak W, Bøg M, Bendixen T, et al. · 2026
- In T2D inadequately controlled with metformin, orforglipron reduced HbA<sub>1c</sub> more than oral semaglutide at 52 wkLau D, ACP Journal Club Editorial Team at McMaster University. · 2026
Research volume (OpenAlex topic graph)
Human clinical evidence
Semantic Scholar · AI TLDRs · influence-rankedMost influential human studies
- Orforglipron (LY3502970), a novel, oral non‐peptide glucagon‐like peptide‐1 receptor agonist: A Phase 1b, multicentre, blinded, placebo‐controlled, randomized, multiple‐ascending‐dose study in people with type 2 diabetesJournal articleOpen access3 influential / 44 citedE. Pratt, Xiaosu Ma, Rong Liu · Diabetes, obesity and metabolism · 2023
- 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 participantsJournal articleOpen access2 influential / 40 citedE. Pratt, Xiaosu Ma, Rong Liu · Diabetes, obesity and metabolism · 2023
- Orforglipron: A Comprehensive Review of an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity and Type 2 DiabetesReviewU. Kansakar, Stanislovas S. Jankauskas, Shivangi Pande · International Journal of Molecular Sciences · 2026
TLDR This comprehensive review integrates pharmacological, clinical, and mechanistic evidence, critically evaluates the data, identifies knowledge gaps, and outlines future directions for orforglipron in the treatment of type 2 diabetes and obesity.
- Effect of Food Consumption on the Pharmacokinetics, Safety, and Tolerability of Once-Daily Orally Administered Orforglipron (LY3502970), a Non-peptide GLP-1 Receptor AgonistJournal articleXiaosu Ma, Rong Liu, E. Pratt · Diabetes Therapy · 2024
TLDR Given the absence of prandial restrictions, orforglipron may emerge as a convenient oral treatment option for patients with type 2 diabetes or obesity.
- Effect of oral non-peptide GLP-1 receptor agonist orforglipron (LY3502970) in participants with obesity or overweight: A Phase 2 studyJournal articleSean Wharton, Thomas Blevins, L. Connery · Diabetes. Umwelt. Leben. Perspektiven aus allen Blickwinkeln · 2024
Research funding & verification
NIH RePORTER · CrossRef DOI registryPublication landscape
CrossRef · DOI registry- Eli Lilly and Company15 works
- National Natural Science Foundation of China1 works
- National Institutes of Health (NIH): National Heart, Lung, and Blood Institute1 works
- National Institute of Diabetes and Digestive and Kidney Diseases1 works
- NIH1 works
- Eli Lilly Japan1 works
Funder diversity is a credibility signal. Research concentrated in a single drug company's funding warrants more scrutiny than research funded across NIH, charities, and academic grants.
Preprints — cutting edge
bioRxiv · medRxiv · via Europe PMCPreprints have NOT been peer-reviewed. They are early research shared by authors before formal validation. Treat findings as preliminary.
- PreprintOral Small-Molecule GLP-1 Receptor Agonists: Mechanistic Insights and Emerging Therapeutic StrategiesSaldívar-Cerón HI, Vargas-Camacho JA, León-Cabrera S, et al. · 2025-05-13
- PreprintGLP-1R associates with VAPB and SPHKAP at ERMCSs to regulate β-cell mitochondrial remodelling and functionAustin G, Oqua AI, El Eid L, et al. · 2024-04-30 · cited 2×
- PreprintStructural basis of peptidomimetic agonism revealed by small molecule GLP-1R agonists Boc5 and WB4-24Cong Z, Zhou Q, Li Y, et al. · 2022-01-05 · cited 1×
- PreprintMolecular insights into ago-allosteric modulation of the human glucagon-like peptide-1 receptorCong Z, Chen L, Ma H, et al. · 2021-05-29
Known risks
GI side effects similar to injectable GLP-1s. Pancreatitis (rare class signal), gallbladder events, theoretical thyroid C-cell concerns (rodent finding). Cardiovascular and long-term safety still characterizing in Phase 3.
Reported side effects
Nausea, vomiting, diarrhea, constipation, decreased appetite, fatigue.
FDA adverse event reports (FAERS)
Updated quarterly by FDA- US1
Most-reported reactions
- Dyspepsia1
- Nausea1
Counts from FDA Adverse Event Reporting System (FAERS). Voluntary reports — they show what was reported, not whether the drug caused the event. Many reports lack confirmation. FAERS docs
What requires medical supervision
Investigational. Patients should use FDA-approved alternatives until Orforglipron is available via prescription.
Questions for your clinician
- Would I prefer oral over injectable GLP-1 if both were available?
- What's the timeline for Orforglipron approval?
- Is there a clinical trial site near me?