Orforglipron dosing evidence
Orforglipron has a published human dose, and it comes from an approved label rather than from a trial someone reinterpreted. It is FDA-approved and prescription-only, sold as FOUNDAYO, indicated alongside a reduced-calorie diet and increased physical activity for adults with obesity, or adults with overweight plus at least one weight-related comorbidity. It is also the first orally dosed small-molecule GLP-1 receptor agonist: a non-peptide taken as one tablet once daily, with or without food. Nothing about it is reconstituted, diluted or injected, which is why this page carries no mixing calculator. The label directs swallowing tablets whole, never breaking, crushing or chewing them, and never taking more than one per day. Because this is a new formulation class, its tablet strengths bear no relationship to the milligram numbers used for injected GLP-1 peptides. The published range, and the label section it is quoted from, are below.
Curated by Dosavy from published literature and regulator labels. Published 11 September 2026, last reviewed 11 September 2026. No clinician reviews this page.
What the evidence says
| Experience | Route | Range | Frequency |
|---|---|---|---|
| Beginner | Oral | 0.8 mg[1]Label starting dosage: 'The starting dosage is 0.8 mg orally once daily.' Held for at least 30 days before the first increase. The escalation exists specifically 'to reduce the risk of gastrointestinal (GI) adverse reactions'. | Once daily |
| Intermediate | Oral | 2.5–5.5 mg[1]The two mandatory escalation steps. 'After at least 30 days on the 0.8 mg dosage, increase the dosage to 2.5 mg once daily. After at least 30 days on the 2.5 mg dosage, increase the dosage to 5.5 mg once daily.' Each step is a minimum of 30 days, so 5.5 mg is not reached before roughly week 9. | Once daily |
| Advanced | Oral | 9–17.2 mg[1]The optional higher dosage levels. 'The 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. The maximum dosage of FOUNDAYO is 17.2 mg once daily.' Reaching 17.2 mg from the 0.8 mg start takes a minimum of about 5 months. When a strong CYP3A4 inhibitor is taken concomitantly the maximum drops to 9 mg once daily. | Once daily |
- BeginnerOral
0.8 mg[1]
Once daily
Label starting dosage: 'The starting dosage is 0.8 mg orally once daily.' Held for at least 30 days before the first increase. The escalation exists specifically 'to reduce the risk of gastrointestinal (GI) adverse reactions'.
- IntermediateOral
2.5–5.5 mg[1]
Once daily
The two mandatory escalation steps. 'After at least 30 days on the 0.8 mg dosage, increase the dosage to 2.5 mg once daily. After at least 30 days on the 2.5 mg dosage, increase the dosage to 5.5 mg once daily.' Each step is a minimum of 30 days, so 5.5 mg is not reached before roughly week 9.
- AdvancedOral
9–17.2 mg[1]
Once daily
The optional higher dosage levels. 'The 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. The maximum dosage of FOUNDAYO is 17.2 mg once daily.' Reaching 17.2 mg from the 0.8 mg start takes a minimum of about 5 months. When a strong CYP3A4 inhibitor is taken concomitantly the maximum drops to 9 mg once daily.
Published ranges, reported as the literature states them and numbered to the sources at the foot of this page. Not a recommendation.
Orforglipron at a glance
- Category
- GLP-1
- Half-life
- 29–49 h
- Routes
- Oral
- Regulatory status
- Approved
- Also sold as
- Foundayo, LY3502970, oral GLP-1 receptor agonist, non-peptide GLP-1 agonist
Mechanism
A non-peptide, orally bioavailable small-molecule GLP-1 receptor agonist. It binds to and activates the human GLP-1 receptor; GLP-1 is a physiological regulator of appetite and caloric intake, and GLP-1 receptors are present in brain regions that regulate appetite. In animal studies orforglipron distributed to and activated neurons in those appetite-regulating regions. Because it is a small molecule rather than a peptide, it is absorbed orally without a permeation enhancer and without food or water restrictions, and it is cleared hepatically via CYP3A4, a metabolic route peptide GLP-1 agonists do not have.
Reconstitution
An oral tablet. Nothing is reconstituted, diluted or injected. Swallow tablets whole (the label directs that they must not be broken, crushed or chewed) and never take more than one tablet per day.
Storage
Store at room temperature, 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C and 30°C. Supplied in bottles with a desiccant and a child-resistant closure; keep in the original bottle.
Frequency in practice
One tablet orally once daily, with or without food.
Regulatory
FDA-approved and prescription-only, marketed as FOUNDAYO, indicated 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 in adults with overweight plus at least one weight-related comorbidity. This is a genuinely new formulation class (the first orally dosed small-molecule GLP-1 receptor agonist), so oral tablet strengths here have no relationship to the milligram numbers used for injected GLP-1 peptides.
What to know before anything else
BOXED WARNING: Thyroid C-cell tumors have been observed in rodents with GLP-1 receptor agonists that are pharmacologically active in rats and mice. Orforglipron itself is not pharmacologically active in rats or mice and did not produce tumors in rodents, but it is active at the human GLP-1 receptor and the human relevance of the class finding has not been determined. The boxed warning and the MTC/MEN 2 contraindication still apply.
Contraindicated with a personal or family history of medullary thyroid carcinoma (MTC) or with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
Contraindicated after a known serious hypersensitivity reaction to orforglipron or any excipient.
LIMITATION OF USE ON THE LABEL: concomitant use with another GLP-1 receptor agonist is not recommended. Stacking orforglipron with semaglutide, tirzepatide or any other incretin agonist is outside the approved use.
Acute pancreatitis has been observed with GLP-1 receptor agonists including orforglipron; discontinue if pancreatitis is suspected. Acute gallbladder disease has been reported in clinical trials.
Severe gastrointestinal reactions occur; not recommended in patients with severe gastroparesis. Acute kidney injury due to volume depletion has been reported. Monitor renal function if vomiting or diarrhoea occurs.
Combining with insulin or an insulin secretagogue increases the risk of hypoglycaemia, including severe hypoglycaemia.
CYP3A4 interaction is specific to this drug and clinically load-bearing: the maximum dosage is 9 mg once daily when taken with a strong CYP3A4 inhibitor, strong CYP3A4 inhibitors that also inhibit OATP1B (e.g. ritonavir) should be avoided entirely, and strong CYP3A4 inducers should be avoided.
Do not exceed simvastatin 20 mg once daily when taken with orforglipron.
Orforglipron delays gastric emptying and can affect absorption of other oral medications.
Pulmonary aspiration during general anesthesia or deep sedation has been reported with GLP-1 receptor agonists; tell any anesthetist about current use before an elective procedure.
If 7 or more consecutive doses are missed, the label directs restarting dosage escalation at a lower dosage rather than resuming the previous dose.
Reviewed interactions
These are the pairs Dosavy holds reviewed, cited data on. A combination that is not listed here has not been assessed, which is not the same as being safe.
- Dangerouswith Retatrutide
Do not combine. Orforglipron's label carries an explicit limitation of use (concomitant use with another GLP-1 receptor agonist is not recommended), and retatrutide is a GLP-1 receptor agonist among its three targets. Stacking two agents at the same receptor multiplies the gastrointestinal effects (nausea, vomiting, diarrhoea, dehydration) without a corresponding gain, and retatrutide has no approved label or dose of any kind.[1]
Both activate the GLP-1 receptor. Duplicating agonism at one receptor compounds the class's dose-limiting gastrointestinal and volume-depletion effects rather than adding a new mechanism.
- Dangerouswith Semaglutide
Do not combine. Both labels say so independently: orforglipron's states that concomitant use with another GLP-1 receptor agonist is not recommended, and semaglutide's states that coadministration with any other GLP-1 receptor agonist is not recommended. Switching between them requires stopping one first, not overlapping.[1][2]
Orforglipron is a non-peptide oral GLP-1 receptor agonist and semaglutide a peptide GLP-1 receptor agonist; together they duplicate agonism at the same receptor.
- Dangerouswith Survodutide
Do not combine. Survodutide is a dual glucagon/GLP-1 receptor agonist, so the GLP-1 arm duplicates what orforglipron does, and orforglipron's label explicitly advises against concomitant use with another GLP-1 receptor agonist. Survodutide is also unapproved, with no label defining a maximum dose to reason from.[1]
Both agonise the GLP-1 receptor; survodutide adds glucagon-receptor agonism on top, so the combination is duplicative at one receptor and uncharacterised at the other.
- Dangerouswith Tirzepatide
Do not combine: both labels prohibit it independently. Orforglipron's limitation of use rules out concomitant GLP-1 receptor agonists, and tirzepatide's says coadministration with any GLP-1 receptor agonist is not recommended. If you are switching from one to the other, stop the first before starting the second.[1][3]
Tirzepatide is a GIP and GLP-1 receptor agonist; orforglipron is a GLP-1 receptor agonist. The shared GLP-1 arm is duplicated, compounding gastrointestinal adverse effects and the risk of dehydration and acute kidney injury.
Orforglipron questions
Is there an established dose for orforglipron?
Yes, unusually for this library. Every figure in the range table below is quoted from one source: the FDA prescribing information for FOUNDAYO, dated 2026, sections 2.1 and 2.2. The recorded evidence level is randomised controlled trial, which is what an approval of this kind rests on. The label sets a starting dosage, two mandatory increases and a set of optional higher levels, each held at least 30 days before the next, and it says why the steps exist: to reduce the risk of gastrointestinal adverse reactions. Reaching the maximum from the start therefore takes a minimum of about five months. Two other sources appear at the foot of this page, the 2024 Wegovy label and the 2026 Zepbound label, cited only for what they say about combining GLP-1 receptor agonists.
How does orforglipron work, and why does being a small molecule matter?
It binds and activates the human GLP-1 receptor, the same receptor the injectable GLP-1 peptides act on. GLP-1 is a physiological regulator of appetite and caloric intake, and its receptors sit in brain regions that regulate appetite; in animal studies orforglipron distributed to and activated neurons in those regions. The difference from the injectables is chemical rather than pharmacological. Because it is a small molecule and not a peptide, it is absorbed orally with no permeation enhancer and no food or water restrictions, and it is cleared hepatically through CYP3A4, a route the peptide GLP-1 agonists do not have.
Does orforglipron need to be reconstituted?
No. It is an oral tablet: nothing about it is reconstituted, diluted or injected, and no vial, bacteriostatic water or syringe is involved at any point. The label directs that tablets be swallowed whole, never broken, crushed or chewed, and that no more than one be taken per day. Storage is at room temperature, 20°C to 25°C, in the original bottle with its desiccant.
Can orforglipron be taken with semaglutide, tirzepatide or another GLP-1?
No. The orforglipron label carries an explicit limitation of use: concomitant use with another GLP-1 receptor agonist is not recommended. The labels on the other side say the same independently, which is why they are cited here. Wegovy's advises against coadministration with any other GLP-1 receptor agonist, and Zepbound's says the same. Duplicating agonism at one receptor compounds the class's gastrointestinal effects and its dehydration risk without adding a mechanism, and that covers the unapproved dual and triple agonists too, because their GLP-1 arm is the same arm.
What is the boxed warning on orforglipron, and who should not take it?
The boxed warning is a class warning: thyroid C-cell tumors have been observed in rodents given GLP-1 receptor agonists that are pharmacologically active in rats and mice. Orforglipron itself is not pharmacologically active in rats or mice and produced no tumors in rodents, but it is active at the human GLP-1 receptor, so the human relevance of the class finding has not been determined and the warning still applies. It is contraindicated with a personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2, and after a known serious hypersensitivity reaction to it.
Which drug interactions and adverse effects are specific to orforglipron?
The CYP3A4 route is the one the injectable GLP-1 peptides do not have. The label caps the maximum daily dosage when a strong CYP3A4 inhibitor is taken alongside it, says strong inhibitors that also inhibit OATP1B such as ritonavir should be avoided entirely, says strong inducers should be avoided, and caps simvastatin at 20 mg once daily. Beyond that it records acute pancreatitis and acute gallbladder disease, severe gastrointestinal reactions with a recommendation against use in severe gastroparesis, acute kidney injury from volume depletion, and a higher risk of hypoglycaemia alongside insulin or an insulin secretagogue. It delays gastric emptying, which can change how other oral medicines are absorbed, and pulmonary aspiration during general anesthesia or deep sedation has been reported with this class.
What happens if you miss a week of orforglipron?
If seven or more consecutive doses are missed, the label directs restarting dosage escalation at a lower dosage rather than resuming the previous one. That is not caution for its own sake: the escalation exists to limit gastrointestinal adverse reactions, and tolerance to them is built by holding each step for at least 30 days. Any change to the schedule belongs with the prescriber who wrote it.
Every number above, and where it came from
3 sources, numbered where they are used. Each one links to the paper or the label itself, not to a summary of it.
- [1]FOUNDAYO (orforglipron) tablets, for oral use: FDA prescribing information
2026 · FDA approved label
- [2]WEGOVY (semaglutide) injection, for subcutaneous use: FDA prescribing information
2024 · FDA approved label
- [3]ZEPBOUND (tirzepatide) injection, for subcutaneous use: FDA prescribing information
2026 · FDA approved label
The rest of the math
- Reconstitution calculatorThe full version of the tool above, with syringe barrel sizes and IU conversion.
- Vial longevityHow many doses a vial holds and the date it runs out.
- Cost per doseVial price against doses drawn, so two vial sizes can be compared honestly.
- Half-life and decayFirst-order clearance, time to steady state, and what remains at a given hour.
- GLP-1 titration scheduleEscalation steps and week-by-week timing for GLP-1 receptor agonists.
You worked out the draw. Now log this dose.
A calculator answers once and forgets. Dosavy keeps the concentration you mixed, the doses you actually took, and a reminder for the next one, with the same evidence labels you see on this page.