Orforglipron: research

A daily GLP-1 pill approved in the US for adult weight management.

Also called: LY3502970, LY-3502970, OWL833, Foundayo.

Oral GLP-1 agonists · Nonpeptide GLP-1 receptor agonist · Evidence: Approved drug.

47 started registry studies identified; pivotal ATTAIN and ACHIEVE results support weight and glucose effects. Long-term rare harms remain uncertain.

Studies

Orforglipron dosage

Typical reported dose: 0.8 mg once a day to start, up to 17.2 mg

  • FDA tablets: at least 30 days per step: 0.8 → 2.5 → 5.5 → 9 → 14.5 → 17.2 mg daily; at least 30 days per step. Steps above 5.5 mg depend on response and tolerability. once daily, by mouth. Drug label. Studied in: Adults with obesity, or overweight plus a weight-related condition. (source)
  • ATTAIN-1: 6 mg capsules: 1 mg once daily, then 3 mg once daily, then 6 mg once daily once daily, by mouth. Studied in a trial. Studied in: Adults in ATTAIN-1: weight without diabetes. (source)
  • ATTAIN-1: 12 mg capsules: 1 mg once daily, then 3 mg once daily, then 6 mg once daily, then 12 mg once daily once daily, by mouth. Studied in a trial. Studied in: Adults in ATTAIN-1: weight without diabetes. (source)
  • ATTAIN-1: 36 mg capsules: 1 mg once daily, then 3 mg once daily, then 6 mg once daily, then 12 mg once daily once daily, by mouth. Studied in a trial. Studied in: Adults in ATTAIN-1: weight without diabetes. (source)
  • ATTAIN-2: 6 mg capsules: 1 mg once daily, then 3 mg once daily, then 6 mg once daily once daily, by mouth. Studied in a trial. Studied in: Adults in ATTAIN-2: weight with diabetes. (source)
  • ATTAIN-2: 12 mg capsules: 1 mg once daily, then 3 mg once daily, then 6 mg once daily, then 12 mg once daily once daily, by mouth. Studied in a trial. Studied in: Adults in ATTAIN-2: weight with diabetes. (source)

These are doses reported in labels, trials or user reports, not a personal plan. Check the source behind each one.

Work out syringe units with the dosing calculator

Orforglipron side effects and risks

Reported side effects

  • US boxed warning: thyroid C-cell tumors: Other GLP 1 agonists caused thyroid C cell tumors in rodents; human relevance is unknown. Orforglipron itself is inactive in ordinary rodents and did not cause tumors in its rodent studies., serious. Do not use with personal or family medullary thyroid cancer or MEN2. Report a neck lump, swallowing difficulty or persistent hoarseness. (source)
  • Nausea: Two trials, up to 72 weeks: N=1051/1055/1049 at 5.5/9/17.2 mg equivalents; nausea 26%/34%/35%; placebo 10% (N=1576)., moderate (source)
  • Constipation: 5.5/9/17.2 mg: 20%/27%/24%; placebo 9%., moderate (source)
  • Diarrhea: 5.5/9/17.2 mg: 21%/23%/25%; placebo 11%., moderate (source)
  • Vomiting: 5.5/9/17.2 mg: 13%/21%/24%; placebo 4%., moderate (source)
  • Indigestion: 5.5/9/17.2 mg: 12%/16%/13%; placebo 4%., moderate (source)
  • Abdominal pain: 5.5/9/17.2 mg: 13%/14%/14%; placebo 7%., moderate (source)
  • Headache: 5.5/9/17.2 mg: 8%/9%/9%; placebo 7%., mild (source)
  • Bloating: 5.5/9/17.2 mg: 7%/9%/8%; placebo 3%., mild (source)
  • Fatigue: 5.5/9/17.2 mg: 6%/7%/9%; placebo 4%., moderate (source)
  • Burping: 5.5/9/17.2 mg: 6%/8%/8%; placebo 1%., mild (source)
  • Acid reflux: 5.5/9/17.2 mg: 6%/6%/7%; placebo 2%., moderate (source)
  • Gas: 5.5/9/17.2 mg: 5%/6%/6%; placebo 2%., mild (source)
  • Hair loss: 5.5/9/17.2 mg: 4%/4%/5%; placebo 2%., mild (source)

Stop and get help if

  • Persistent severe abdominal pain, especially into the back, with or without vomiting: Stop the drug and seek urgent care for possible pancreatitis.
  • Face or throat swelling, trouble breathing, or fainting with an allergic reaction: Stop the drug and get emergency care now.
  • Repeated vomiting, inability to keep fluids down, very little urine, or fainting: Seek urgent care for dehydration or kidney injury.
  • Sudden vision loss or a major new vision change: Get urgent eye care; do not wait for the next routine visit.
  • Confusion, seizure, or low blood sugar that does not improve: Get emergency help; severe low blood sugar needs immediate care.
  • Upper-right abdominal pain with fever, yellow eyes, or dark urine: Seek urgent assessment for gallbladder or liver disease.
  • Chest pain, fainting, or a sustained racing heartbeat: Seek urgent care; severe chest pain or collapse needs emergency help.
  • A new neck lump, trouble swallowing, or persistent hoarseness: Arrange prompt clinical assessment for a thyroid warning sign.
  • Severe bloating with vomiting, or inability to pass stool or gas: Seek urgent medical assessment for possible bowel blockage.

Who should avoid it

  • pregnant: Weight loss offers no pregnancy benefit and may harm the fetus. The label says to stop when pregnancy is recognized.
  • breastfeeding: Not recommended while nursing; human milk and infant-effect data are absent.
  • tryingToConceive: The US label gives no specific waiting period before conception.
  • under18: Pediatric safety and effectiveness are not established; registered pediatric trials do not authorize routine use.
  • mtcOrMen2: FDA contraindication: personal or family history of medullary thyroid cancer, or MEN2.
  • other: Known serious allergy to orforglipron or tablet ingredients is an FDA contraindication.
  • eatingDisorderHistory: This is a screening policy, not an FDA contraindication.
  • pancreatitisHistory: Discuss prior pancreatitis before use; stop and seek care for persistent severe abdominal pain.
  • gastroparesis: Not recommended with severe gastroparesis, where the stomach empties too slowly. The drug can worsen this.
  • gallbladderDisease: Gallstones and gallbladder inflammation occurred in trials.
  • diabeticRetinopathy: Rapid blood-sugar improvement can temporarily worsen diabetes-related eye damage. Eye disease needing urgent treatment was not studied.
  • kidneyDisease: The label requires no dose adjustment for kidney disease, including end-stage disease. Vomiting or diarrhea can still cause dehydration and kidney injury.
  • liverDisease: Not recommended with severe liver impairment (Child-Pugh C); no adjustment for mild or moderate impairment.
  • heartCondition: Heart rate rose about 4–5 beats/min. In high-risk type 2 diabetes, ACHIEVE-4 ruled out a large heart-risk increase versus insulin glargine, without proving lower risk.
  • diabetes: Review glucose-lowering medicines and glucose checks, especially insulin and sulfonylureas.
  • surgeryPlanned: Tell the anesthesia team about use. Delayed stomach emptying may leave food in the stomach despite fasting.

Interactions

  • Other GLP-1 medicines: The label does not recommend another GLP-1 agonist at the same time. Extra benefit is unproven and side effects may add.
  • Insulin: Low blood sugar risk rises. The prescriber may need to lower insulin and increase glucose checks.
  • Sulfonylureas and related secretagogues: Low blood sugar risk rises. Ask the prescriber to review these medicines and blood sugar checks.
  • Strong CYP3A4 inhibitors: These medicines slow Foundayo breakdown. The US label limits Foundayo to 9 mg once daily with a strong CYP3A4 inhibitor; avoid inhibitors that also inhibit OATP1B. Dose changes require the prescriber.
  • Strong CYP3A4 inhibitors that also inhibit OATP1B: Avoid this combination. The label gives ritonavir as an example of dual CYP3A4 and OATP1B inhibition.
  • Cyclosporine: Cyclosporine raised overall orforglipron exposure about 2.6-fold. Review the combination with a clinician.
  • Strong CYP3A4 inducers: The label says to avoid strong CYP3A4 inducers. Carbamazepine reduced orforglipron exposure by 82%.
  • Moderate CYP3A4 inducers: Monitor effectiveness; clinician-directed dose escalation may be needed. Efavirenz reduced modeled exposure by 61%.
  • Simvastatin: Foundayo raises exposure to active simvastatin. The US label limits concomitant simvastatin to 20 mg once daily; ask the prescriber to review the statin before combining them.
  • Oral hormonal contraceptives: Use a non-oral method or add a barrier method for 30 days after starting and 30 days after each dose increase.

Product quality risks

  • A research-use label or a claimed milligram amount does not establish identity, content or pharmaceutical quality.
  • FDA warns about unapproved GLP-1 products and dosing errors; these class warnings do not measure orforglipron counterfeit prevalence.
  • Trial capsules and approved tablets have different exposure per milligram. Copying a capsule dose onto an unverified tablet can misdose.
  • No independent test-purchase series or compound-specific poison-center dataset for online orforglipron was located.

How Orforglipron works

It mimics GLP-1, a gut hormone that reduces hunger and slows stomach emptying. It helps the pancreas release insulin when blood sugar is high.

  • GLP-1 receptor: Reduces appetite and food intake; supports glucose-dependent insulin release.

Half-life: About 29–49 hours after an oral dose.

Gaps: Some registered PK studies do not disclose all numeric dose levels. Those gaps are stated rather than filled with guessed schedules. Four phase 1b schedules remain incomplete. The Japanese supplement caption conflicts with its dose figure; no complete Japanese schedule is inferred. ATTAIN-J has registry results but no located primary results paper. It has no published-trial dosing protocol here. Published trial and registry estimands can differ. Primary pivotal estimates use the journal analysis; secondary registry records retain their own labels. No independent clinician-published alternative dose schedule was verified; clinical-practice protocols are therefore absent. No controlled evidence supports longevity microdosing, alternate-day maintenance, planned cycling or concurrent tirzepatide use. Community prevalence is unknown. Reports are a convenience sample; nMentions counts only specified actual-use accounts. Pregnancy, nursing, pediatric use and an exact preconception washout remain unresolved. Rare thyroid cancer, severe liver injury and longer-term cardiovascular or kidney benefit need continued study. ACHIEVE-4 established noninferiority to glargine with an HR margin of 1.8; it did not establish cardiovascular superiority. FDA required additional thyroid, pancreatic, aspiration, liver and lactation surveillance. Current completion or regulatory acceptance of every requirement was not verified. No orforglipron-specific PCAC vote or warning letter was located. FDA nomination categories were searched; absence is not a blanket ban after drug approval. No compound-specific analytical survey of unregulated products was located; contamination rates and counterfeit prevalence are unknown. Independent trials are counted by registry, excluding three umbrella/screening records and four not-yet-recruiting studies. Publications and meta-analyses overlap those trials. Some complex formulation and drug-probe schedules remain in the linked registries rather than being compressed into unsafe dosing instructions. No named orforglipron entry was found in the searched FDA 503A nomination categories or 503B nomination and bulks lists; approved-component rules are separate. The approved label flags thyroid C-cell tumors, but orforglipron itself did not produce rodent tumors and is inactive at ordinary rodent GLP-1 receptors.

Related to Orforglipron

Orforglipron: the short version

Sources

Sources checked: 2026-10-18.

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