Orforglipron

Dosing from the Literature

Published for fat loss: the Foundayo label's 0.8 to 17.2 mg once a day, built up monthly; the Phase 3 weight-loss trials used 6–36 mg of the trial formulation. Not published: nothing missing; the dose is on the label.

The three placebo-controlled Phase 3 trials below each tested three once-daily doses, reached by raising the dose every 4 weeks from 1 mg (ClinicalTrials.gov NCT05971940, NCT05869903, NCT05872620). The Foundayo label, approved April 1, 2026, uses different tablet strengths (0.8, 2.5, 5.5, 9, 14.5 and 17.2 mg); its titration is summarized below the table.

What It Is

Orforglipron (development code LY3502970) is an oral, non-peptide, small-molecule agonist of the glucagon-like peptide-1 receptor (GLP-1R) developed by Eli Lilly and approved by the FDA on April 1, 2026 as Foundayo (NDA 220934). The molecule was originally discovered by Chugai Pharmaceutical in Japan and licensed to Eli Lilly in 2018. It is taxonomically distinct from every other GLP-1 receptor agonist currently approved or in advanced development: all other approved GLP-1 RAs (exenatide, liraglutide, dulaglutide, semaglutide) are peptides, and oral semaglutide (Rybelsus) depends on the absorption-enhancer SNAC plus a 30-minute fasting window with ≤120 mL of water to achieve any meaningful bioavailability. Orforglipron is a true small molecule — it survives the gastrointestinal environment and requires no food or water restriction at dosing (Ma et al., 2024).

Mechanistically, orforglipron activates GLP-1R from a non-peptide binding pocket structurally distinct from the orthosteric peptide-binding site. Kawai and colleagues (PNAS 2020) published the cryo-EM structure of the GLP-1R–orforglipron complex, revealing the molecular basis for small-molecule activation — the compound binds a pocket spanning the extracellular side of transmembrane helices 1, 2, 3, and 7, inducing conformational changes that propagate to the intracellular Gαs-coupling site. The pharmacodynamic signature at downstream effectors (cAMP, insulin secretion, gastric emptying, appetite) is functionally similar to the peptide agonist class, though biased-agonism differences at the β-arrestin arm produce distinct receptor-desensitization kinetics.

Orforglipron has advanced rapidly through the clinical development pathway. Phase 1 single- and multiple-ascending-dose studies in healthy volunteers (Pratt 2023, Diabetes Obes Metab 25:2634-2641) established the PK / PD foundation. Phase 1b in T2D (Pratt 2023, PMID 37264711) confirmed HbA1c and body weight reductions. Phase 2 dose-finding in T2D (Frias et al., Lancet 2023; 402:472-483) and obesity (Wharton et al., N Engl J Med 2023;389:877-888; PMID 37351564) established efficacy across a broad dose range with safety consistent with the injectable GLP-1 class. The Phase 3 program — ACHIEVE for type 2 diabetes and ATTAIN for obesity — reported pivotal positive results in 2025.

The FDA approved orforglipron on April 1, 2026 as Foundayo tablets (NDA 220934; original approval, new molecular entity, per openFDA Drugs@FDA). Eli Lilly's global regulatory submissions followed the ATTAIN-2 readout (August 26, 2025). Foundayo needs neither an injection nor the food / water restrictions of oral semaglutide.

Mechanism of Action

• Non-peptide GLP-1R agonism — In the cryo-EM structure, orforglipron binds high in the receptor's helical bundle, contacting its extracellular domain, extracellular loop 2 and transmembrane helices 1, 2, 3 and 7 but not 4, 5 or 6; native GLP-1 contacts every helix except TM4. It activates the receptor's Gαs–cAMP pathway as a partial agonist relative to native GLP-1 (Kawai et al., 2020).
• Glucose-dependent insulinotropic effect — Foundayo stimulates insulin release in the presence of raised blood glucose (Foundayo label). In anesthetized monkeys, intravenous orforglipron did not raise insulin before a glucose load and raised it after, about as much as exenatide (Kawai et al., 2020). With orforglipron as the only diabetes drug, ACHIEVE-1 reported no severe hypoglycemia (Rosenstock et al., 2025).
• Delayed gastric emptying — Foundayo delays gastric emptying; the delay is largest after the first dose and diminishes over time (Foundayo label). In healthy adults, gastric emptying was delayed on day 28 of daily dosing (Pratt et al., 2023; PMID 37344954).
• Central appetite effects — GLP-1 receptors are present in brain regions that regulate appetite; in animal studies orforglipron reached and activated neurons in those regions, and the label says Foundayo's lower food intake is likely due to decreased appetite (Foundayo label). In monkeys, oral orforglipron cut food intake about as much as injectable exenatide (Kawai et al., 2020).
• Pharmacokinetics — once-daily oral — Peak levels come 4 to 8 hours after a dose and the half-life is about 29 to 49 hours, with steady state after about a week of daily dosing (Foundayo label); the phase 1 investigators concluded that the long half-life allows once-daily dosing (Pratt et al., 2023; PMID 37344954). In two phase 1 studies, food lowered exposure by about 18–24%, a difference the authors judged unlikely to matter clinically (Ma et al., 2024).
• CYP metabolism — Orforglipron is broken down mainly by the liver enzyme CYP3A4 and leaves the body mostly in feces (87% of a dose), with under 1% in urine. Clarithromycin, a strong CYP3A4 inhibitor, raised its exposure 3.5-fold, and carbamazepine, a strong inducer, cut it by 82% (Foundayo label).
• Species cross-reactivity note — Orforglipron is inactive at mouse, rat, rabbit and dog GLP-1 receptors: its binding needs a tryptophan (Trp33) found in primate receptors, so its efficacy was tested in mice carrying the human receptor and in monkeys (Kawai et al., 2020). The label states it is not pharmacologically active in rats, mice or rabbits (Foundayo label).
• Biased-agonism profile — In cells, orforglipron was a partial agonist for cAMP with no detectable β-arrestin recruitment, yet in mice carrying the human receptor it lowered glucose as much as the full agonist exenatide; the authors proposed a large receptor reserve, and that its distinct receptor conformation may explain the partial, biased signaling (Kawai et al., 2020).
• No GIP receptor activity — In cell assays, orforglipron did not activate the human GIP receptor (Kawai et al., 2020).
• No glucagon receptor activity — The same assays showed no activity at the human glucagon or GLP-2 receptors (Kawai et al., 2020).
• Oral bioavailability — After a 0.8 mg dose, its absolute bioavailability was 77% (Foundayo label); oral semaglutide, which is formulated with an absorption enhancer, has an oral bioavailability under 1% (Kawai et al., 2020).

What the Research Shows

• Phase 1 healthy volunteers (Pratt 2023) — Single- and multiple-ascending-dose study establishing PK, safety, and pharmacodynamic effects in healthy adults (Diabetes Obes Metab 25:2634-2641).
• Phase 1b T2D (Pratt 2023, PMID 37264711) — Multiple-ascending-dose in T2D patients; meaningful HbA1c and body-weight reductions with AE profile consistent with the GLP-1 class.
• Phase 2 T2D dose-finding (Frias 2023, Lancet 402:472-483) — 26-week dose-response in adults with T2D; dose-dependent HbA1c reductions, body-weight reductions, and GI-predominant AE profile.
• Phase 2 obesity (Wharton 2023, NEJM 389:877-888; PMID 37351564) — 36-week Phase 2 in adults with obesity. Weight reductions scaled with dose; highest-dose cohort achieved body-weight reductions approaching injectable semaglutide benchmarks.
• Phase 3 ACHIEVE-1 (Rosenstock 2025, NEJM 393:11; PMID 40544435; NCT05971940) — Phase 3, double-blind, placebo-controlled trial in 559 adults with early T2D treated by diet / exercise alone. 1:1:1:1 randomization to orforglipron 3, 12, 36 mg or placebo once daily for 40 weeks. Significant HbA1c reduction across all three doses vs placebo; body-weight reductions (4.5–7.6% vs 1.7%) scaled with dose.
• Phase 3 ATTAIN-1 obesity (Wharton 2025, NEJMoa2511774) — 72-week multinational phase 3 in adults with obesity / overweight. Weight reductions of −7.5% (6 mg), −8.4% (12 mg), −11.2% (36 mg) vs −2.1% placebo (all p<0.001). 54.6% of the 36-mg cohort achieved ≥10% weight reduction; 36.0% achieved ≥15%; 18.4% achieved ≥20%.
• Phase 3 ATTAIN-2 obesity + T2D (NCT05872620) — 1,613 adults with obesity or overweight and type 2 diabetes, 72 weeks. On 36 mg once daily, weight fell 10.5% vs 2.2% on placebo and HbA1c 1.8 points vs 0.1, counting data while people stayed on treatment; 75% of the 36-mg group reached an HbA1c below 6.5%, vs 11% on placebo (ClinicalTrials.gov). Counting everyone randomized, weight fell 9.6% vs 2.5% (Foundayo label).
• Additional Phase 3 program — ACHIEVE-2 to -5 in T2D on background metformin or other oral drugs, or insulin glargine (ACHIEVE-5), and a trial of weight maintenance after switching from injectable tirzepatide or semaglutide (ClinicalTrials.gov NCT06584916).
• Structural biology (Kawai 2020, PNAS; PMID 33177239) — Cryo-EM structure of GLP-1R bound to orforglipron (LY3502970) defining the non-peptide binding pocket and mechanism of small-molecule receptor activation.
• Food-effect study (Ma 2024, Diabetes Ther; PMID 38402332) — No clinically meaningful food effect on orforglipron PK — distinct from oral semaglutide, which requires fasting administration.
• Cardiovascular signal — Consistent-with-class reductions in systolic blood pressure, triglycerides, and non-HDL cholesterol reported in ATTAIN-2. In ACHIEVE-4, a cardiovascular safety trial against insulin glargine in adults with type 2 diabetes and established cardiovascular or kidney disease, major cardiovascular events occurred in 4.2% on orforglipron and 5.0% on insulin glargine over a median of 2 years, within the trial’s non-inferiority margin (Klein et al., 2026); a placebo-controlled outcomes trial is still recruiting (ClinicalTrials.gov).

Human Data

• Phase 1 SAD/MAD healthy volunteers — Pratt 2023 (Diabetes Obes Metab 25:2634-2641). PK, safety, and pharmacodynamic foundation.
• Phase 1b T2D MAD (PMID 37264711) — Pratt 2023. Meaningful HbA1c and body-weight reductions.
• Phase 2 T2D (Frias 2023, Lancet 402:472-483) — Dose-response in T2D.
• Phase 2 obesity (Wharton 2023, NEJM; PMID 37351564) — 36-week obesity efficacy and safety.
• Phase 3 ACHIEVE-1 (Rosenstock 2025, NEJM; PMID 40544435; NCT05971940) — Early T2D, 40 weeks. Pivotal HbA1c data.
• Phase 3 ATTAIN-1 (Wharton 2025, NEJM; NEJMoa2511774) — Obesity, 72 weeks. Pivotal weight-loss data.
• Phase 3 ATTAIN-2 (2025 topline) — Obesity + T2D comorbidity.
• Phase 3 ACHIEVE-4 (Klein 2026, Lancet; PMID 42815506; NCT05803421) — Cardiovascular safety against insulin glargine: 2,749 adults with type 2 diabetes, a BMI of 25 or more and established cardiovascular or chronic kidney disease, on up to three glucose-lowering drugs, randomized open-label at 317 sites in 16 countries and territories to once-daily oral orforglipron at the highest dose each tolerated (up to a 36 mg capsule, equivalent to a 17.2 mg tablet) or titrated insulin glargine. Over a median of 2 years, cardiovascular death, non-fatal heart attack, non-fatal stroke or hospitalization for unstable angina occurred in 57 of 1,358 on orforglipron (4.2%) and 67 of 1,343 on insulin glargine (5.0%), a hazard ratio of 0.84 (95% CI 0.59–1.20), within the trial’s non-inferiority margin of 1.8. Gastrointestinal adverse events: 62.1% against 14.2%; clinically significant or severe low blood sugar: 6.8% against 19.2%; deaths: 1.4% against 3.2%. Funded by Eli Lilly; the abstract was read, the full text is paywalled.
• Phase 3 ACHIEVE-2, -3 and -5 — T2D on background oral drugs (ACHIEVE-2 and -3) or insulin glargine (ACHIEVE-5) (ClinicalTrials.gov).
• Additional ATTAIN / ACHIEVE trials — Maintenance, cardiovascular outcomes, adolescent obesity, sleep apnea, hypertension and other groups (ClinicalTrials.gov).
• Pharmacokinetics across populations — PK characterization in Japanese, elderly, and renal / hepatic subpopulations to support global approval.

Reconstitution & Storage

Foundayo is a film-coated tablet taken by mouth, so there is nothing to reconstitute (Foundayo label).

• No injection supplies needed — Pens, needles, sharps disposal irrelevant.
• No food restriction — Taken with or without food (Foundayo label); oral semaglutide is taken at least 30 minutes before the first food of the day (Ma et al., 2024).
• No water restriction — The phase 2 diabetes trial gave it with no food or water restrictions (Frias et al., 2023); oral semaglutide is taken with no more than about 120 mL of water (Ma et al., 2024).
• Once-daily dosing — One tablet once a day, and no more than one a day; the label sets no time of day (Foundayo label).
• No cold-chain requirement — Stored at room temperature (Foundayo label).

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Side Effects & Risks

• GI adverse events (class effect) — In the two weight-loss trials behind the label, stomach and bowel side effects occurred in 60–69% of people on Foundayo vs 37% on placebo, more often at higher doses: nausea 26–35% (placebo 10%), constipation 20–27% (9%), diarrhea 21–25% (11%), vomiting 13–24% (4%) and dyspepsia 12–16% (4%). Most were mild or moderate; nausea, vomiting and diarrhea were most frequent during dose escalation and decreased over time; and 3–6% stopped the drug because of them, vs 0.7% on placebo (Foundayo label). ATTAIN-1's investigators found the side-effect profile consistent with other GLP-1 drugs (Wharton et al., 2025).
• Abdominal pain / discomfort — Abdominal pain was reported in 13–14% of people on Foundayo vs 7% on placebo, and a swollen belly (abdominal distension) in 7–9% vs 3% (Foundayo label).
• Decreased appetite / early satiety — Foundayo decreases food intake, which the label says is likely due to decreased appetite (Foundayo label).
• Hypoglycemia — With orforglipron as the only diabetes drug, ACHIEVE-1 reported no severe hypoglycemia (Rosenstock et al., 2025). In ATTAIN-2, blood glucose below 54 mg/dL occurred in 2% on orforglipron vs 0.2% on placebo, and in 7% of those also taking a sulfonylurea vs 0.5% of those not; the label lists a higher risk with insulin too, and notes that a lower insulin or sulfonylurea dose may reduce it (Foundayo label).
• Gallbladder adverse events — The label links Foundayo and GLP-1 receptor agonists to more acute gallbladder disease. In the two weight-loss trials, gallstones (cholelithiasis) were reported in 1% vs 0.7% on placebo and acute cholecystitis in 0.4% vs 0.3%; the events were associated with weight reduction (Foundayo label).
• Pancreatitis — Acute pancreatitis has been reported with Foundayo, and fatal and non-fatal hemorrhagic or necrotizing pancreatitis with GLP-1 receptor agonists. In the two weight-loss trials, adjudication confirmed it in 6 people on Foundayo (0.14 per 100 patient-years) vs 1 on placebo (0.04); the label directs stopping the drug if pancreatitis is suspected (Foundayo label).
• Thyroid C-cell tumors (boxed warning) — GLP-1 drugs that are active in rats and mice cause thyroid C-cell tumors in them; orforglipron is not active in rats or mice and did not produce tumors in rodent studies, and the human relevance of the rodent tumors has not been determined. Foundayo carries the boxed warning and is contraindicated in people with a personal or family history of medullary thyroid carcinoma (MTC) or with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) (Foundayo label).
• Diabetic retinopathy — The label reports temporary worsening of diabetic retinopathy with rapid improvement in glucose control, and calls for monitoring people with a history of retinopathy for progression (Foundayo label).
• Cardiovascular — In ATTAIN-1, systolic blood pressure, triglycerides and non-HDL cholesterol improved vs placebo (Wharton et al., 2025); in ATTAIN-2, blood pressure and triglycerides improved on all three doses and non-HDL cholesterol on the top dose, in analyses not controlled for multiplicity (Foundayo label). In the weight-loss trials, heart rate rose 4–5 beats per minute on average vs 0.5 on placebo, tachycardia was reported in 3% vs 0.9%, and low blood pressure in 2% vs 0.5% (Foundayo label). A placebo-controlled cardiovascular outcomes trial in adults with atherosclerotic cardiovascular disease or chronic kidney disease is recruiting, with primary completion estimated for August 2031 (ClinicalTrials.gov NCT07241390).
• CYP3A4 drug interactions — Strong CYP3A4 inhibitors raise orforglipron exposure and inducers lower it. The label caps the dose at 9 mg with a strong CYP3A4 inhibitor; says to avoid strong inhibitors that also block OATP1B, such as ritonavir, and strong CYP3A4 inducers; calls for watching effectiveness, and raising the dose as needed, with moderate inducers; and limits simvastatin to 20 mg a day, since Foundayo doubled exposure to its active form (Foundayo label).
• Pregnancy and lactation — The label says weight loss offers no benefit in pregnancy and may cause fetal harm, and to stop Foundayo when pregnancy is recognized; there are no adequate studies in pregnancy, and animal studies suggest there may be risks to the fetus. It advises effective contraception and, because slower stomach emptying may affect oral drugs, switching from an oral contraceptive to a non-oral method, or adding a barrier method, for 30 days after starting and after each dose increase. It does not recommend Foundayo while breastfeeding (Foundayo label).
• Renal / hepatic impairment — The label sets no dose change for kidney impairment (exposure was unchanged even in end-stage kidney disease) or for mild or moderate liver impairment, and does not recommend Foundayo in severe liver impairment (Child-Pugh C), where exposure rose 4.6-fold (Foundayo label).

Bloodwork & Monitoring

The Foundayo label sets no routine lab schedule. What it lists, and what the trials measured:

• HbA1c — The label, which is for weight management, sets no HbA1c schedule. In ATTAIN-2, in adults with type 2 diabetes, HbA1c fell 1.2–1.7 points over 72 weeks from a baseline of 8%, vs 0.4 on placebo (Foundayo label).
• Blood glucose — In people with diabetes, the label calls for monitoring blood glucose before starting and during treatment, and notes that a lower insulin or sulfonylurea dose may reduce the risk of hypoglycemia (Foundayo label).
• Kidney and liver function — The label calls for monitoring kidney function in people with side effects that could deplete fluids, such as vomiting or diarrhea, especially while the dose is started and raised. It sets no dose change for kidney impairment and does not recommend Foundayo in severe liver impairment (Foundayo label).
• Lipid panel — In ATTAIN-1, triglycerides fell 10–20% over 72 weeks vs 4% on placebo, and non-HDL cholesterol 5–8% vs 2%; these results were not controlled for multiplicity (Foundayo label).
• Body weight / body composition — Percent change in body weight was the weight-loss trials' primary end point (Wharton et al., 2025), and the label reports greater loss of fat mass than of lean mass (Foundayo label).
• Blood pressure and heart rate — In ATTAIN-1, systolic pressure fell 5.1–6.4 mmHg over 72 weeks vs 1.4 on placebo, and pulse rose 3.6–4.6 beats per minute vs 0.6. Low blood pressure was reported in 2% of people on Foundayo vs 0.5% on placebo, and in 4% of those also taking blood-pressure drugs (Foundayo label).
• Pancreas-related symptoms — The label calls for watching for signs of acute pancreatitis after starting, such as persistent or severe abdominal pain, sometimes spreading to the back, and stopping the drug if it is suspected. In the weight-loss trials, pancreatic amylase rose 16–20% and lipase 26–31% on average, vs 3% and 4% on placebo; the label calls their significance unknown without other signs of pancreatitis (Foundayo label).
• Gallbladder symptoms — If cholecystitis is suspected, the label calls for gallbladder diagnostic studies and clinical follow-up (Foundayo label).
• Thyroid — The label calls routine calcitonin or thyroid ultrasound monitoring of uncertain value for finding medullary thyroid cancer early, and says thyroid nodules found on examination or imaging, or a raised calcitonin, should be further evaluated (Foundayo label).
• Diabetic retinopathy — The label calls for monitoring people with a history of diabetic retinopathy for progression; Foundayo was not studied in people with retinopathy or macular edema needing acute treatment (Foundayo label).

Commonly Stacked With

Orforglipron is a prescription drug, not a research peptide. The cards below describe the diabetes drugs its trials enrolled people on, and what the Foundayo label says about combinations.

Stacking this? Read the receipt →

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What to Expect — Timeline (Phase 3 data)

What the label and the Phase 3 trials report at each stage, in the people they enrolled:

• Weeks 1–4 (titration start) — The Foundayo label starts at 0.8 mg once daily for at least 30 days. In the two weight-loss trials, nausea, vomiting and diarrhea were most frequent during dose escalation and decreased over time (Foundayo label).
• Weeks 4–12 — On the label, the dose rises to 2.5 mg after at least 30 days and to 5.5 mg after at least 30 more (Foundayo label). In ATTAIN-1 the dose rose every 4 weeks from 1 mg, reaching 36 mg at week 20 (ClinicalTrials.gov NCT05869903).
• Week 40 (ACHIEVE-1 endpoint) — In 559 adults with early type 2 diabetes, HbA1c fell 1.24, 1.47 and 1.48 points on 3, 12 and 36 mg vs 0.41 on placebo, all significantly more than placebo, and weight fell 4.5–7.6% vs 1.7% (Rosenstock et al., 2025).
• Week 72 (ATTAIN-1 endpoint) — In 3,127 adults with obesity or overweight, without diabetes, mean weight change was −7.5% on 6 mg, −8.4% on 12 mg and −11.2% on 36 mg vs −2.1% on placebo; 54.6% of the 36-mg group lost at least 10% of their weight, 36.0% at least 15% and 18.4% at least 20% (Wharton et al., 2025).
• Individual variability — Responses on 36 mg in ATTAIN-1 ranged widely: 18.4% lost at least 20% of their weight, while 45.4% lost less than 10% (Wharton et al., 2025).
• Non-responders — In ATTAIN-1, 28.5% of people on the top dose lost less than 5% of their weight at 72 weeks, vs 73.2% on placebo; the label raises the dose beyond 5.5 mg, up to 17.2 mg, based on treatment response and tolerability (Foundayo label).

Quick Compare — Orforglipron vs Oral Semaglutide vs Injectable GLP-1 Class

Orforglipron (Foundayo, approved April 1, 2026) enters a crowded GLP-1-class market. Comparing it to the closest clinical alternatives:

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References

1. Rosenstock J, Hsia S, Nevarez Ruiz L, Eyde S, Cox D, Wu WS, Liu R, Li J, Fernández Landó L, Denning M, Ludwig L, Chen Y; ACHIEVE-1 Trial Investigators. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes. N Engl J Med. 2025;393(11):1001-1013. PMID: 40544435. DOI: 10.1056/NEJMoa2505669. NCT05971940.
2. Wharton S, Aronne LJ, Stefanski A, Pratt E, Liu R, Hayes PS, Ahmad NN, Li B, Fernández Landó L, Nunes M, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. N Engl J Med. 2025. DOI: 10.1056/NEJMoa2511774 (ATTAIN-1, 72-week Phase 3 obesity).
3. Wharton S, Blevins T, Connery L, Rosenstock J, Raha S, Liu R, Ma X, Mather KJ, Haupt A, Robins D, Pratt E, Kazda C, Konig M; GZGI Investigators. Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. N Engl J Med. 2023;389(10):877-888. PMID: 37351564.
4. Frias JP, Hsia S, Eyde S, Liu R, Ma X, Konig M, Kazda C, Mather KJ, Haupt A, Pratt E, Robins D, Pyrah I, Hartman ML, Bumol TF. 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. PMID: 37369232.
5. Pratt E, Ma X, Liu R, Robins D, Coskun T, Sloop KW, Haupt A, Benson C. 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 diabetes. Diabetes Obes Metab. 2023;25(9):2642-2649. PMID: 37264711.
6. Pratt E, Ma X, Liu R, Robins D, Haupt A, Coskun T, Sloop KW, Benson C. 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 Obes Metab. 2023;25(9):2634-2641. PMID: 37344954.
7. Kawai T, Sun B, Yoshino H, Feng D, Suzuki Y, Fukazawa M, Nagao S, Wainscott DB, Showalter AD, Droz BA, Kobilka TS, Coghlan MP, Willard FS, Kawabe Y, Kobilka BK, Sloop KW. Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist. Proc Natl Acad Sci U S A. 2020;117(47):29959-29967. PMID: 33177239.
8. Ma X, Liu R, Pratt EJ, Benson CT, Bhattachar SN, Sloop KW. Effect of Food Consumption on the Pharmacokinetics, Safety, and Tolerability of Once-Daily Orally Administered Orforglipron (LY3502970), a Non-peptide GLP-1 Receptor Agonist. Diabetes Ther. 2024;15(4):819-832. PMID: 38402332.
9. Chow E, Yang A, Chung CHL, Chan JCN. A Clinical Perspective of the Multifaceted Mechanism of Metformin in Diabetes, Infections, Cognitive Dysfunction, and Cancer. Pharmaceuticals (Basel). 2022;15(4):442. PMID: 35455439. (Companion metformin pharmacology context for T2D combinations.)
10. Eli Lilly and Company. Lilly's oral GLP-1, orforglipron, is successful in third Phase 3 trial (ATTAIN-2), triggering global regulatory submissions this year for the treatment of obesity. Press release, Aug 26 2025.
11. ClinicalTrials.gov. ACHIEVE-1 (NCT05971940); ATTAIN-1 (NCT05869903); ATTAIN-2 and related Phase 3 protocols under the orforglipron program.
12. Luna Ceron E, Reddy SD, Kattamuri L, et al. Current insights, advantages and challenges of small-molecule glucagon-like peptide 1 receptor agonists: a scoping review. J Brown Hosp Med. 2025;4:19-32. PMID: 40191699.
13. U.S. Food and Drug Administration. FOUNDAYO (orforglipron) tablets, prescribing information; label effective July 29, 2026 (SPL set ID 8ac446c5-feba-474f-a103-23facb9b5c62). openFDA drug label API: https://api.fda.gov/drug/label.json?search=openfda.application_number:NDA220934
14. U.S. Food and Drug Administration. Drugs@FDA, NDA 220934 (FOUNDAYO, Eli Lilly and Company): original approval April 1, 2026. openFDA: https://api.fda.gov/drug/drugsfda.json?search=application_number:NDA220934
15. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (503A categories list), versions updated April 15, April 22 and May 14, 2026. fda.gov/media/94155/download. Read October 3, 2026. (Notice that 12 peptides would leave Category 2 because their nominations were withdrawn; their removal; GHK-Cu, except injectable, back in Category 1.)
16. Klein KR, Wysham C, Tuttle KR, Davies MJ, Cox D, Chen J, Wu WS, Denning M, Liu R, Ludwig L, Meskimen ER. 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 (published online September 30, 2026). PMID: 42815506. DOI: 10.1016/S0140-6736(26)01865-9. NCT05803421. (The abstract was read; the full text is paywalled.)

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