Research information only. PrecisePep is an educational library. It is not medical advice and is not intended to assist, encourage or enable self-administration. The compounds documented here are research chemicals — most are not approved for human use. Read the full disclaimer.
PrecisePep/Peptide Library/Orforglipron
Metabolic & Adipose Regulation
Foundayo® · LY3502970 · oral small-molecule GLP-1
Not a peptide — and that is the entire reason it matters. The first oral small-molecule GLP-1 receptor agonist approved for weight management, made in a chemical plant rather than a peptide synthesiser, with no cold chain and no needle.
Every other GLP-1 agonist in this library is a peptide. That is why they are injected, why they need a cold chain, why they cost what they cost to manufacture, and — indirectly — why a grey market exists for them at all. Orforglipron is not a peptide. It is a small molecule that binds the same receptor, and it was approved on 1 April 2026 as Foundayo for chronic weight management.
The practical differences follow from the chemistry. It is a tablet taken once daily with no food or water restrictions — unlike oral semaglutide, which is a peptide smuggled past the gut with an absorption enhancer and has to be taken fasting, with a small sip of water, thirty minutes before anything else. It can be manufactured by ordinary organic synthesis at a scale and cost that peptide manufacturing does not reach. And it needs no refrigeration.
The trade-off is potency. ATTAIN-1 reported dose-dependent weight loss of 7.5% to 11.2% at 72 weeks against 2.1% on placebo.[1] That is a real effect and it is meaningfully less than injectable semaglutide (roughly 15%), oral semaglutide 25 mg (16.6%) or tirzepatide (roughly 21%). Orforglipron is a convenience and access proposition rather than a potency one, and reading it any other way misunderstands what was approved.
Its approval was also unusually fast — issued 50 days after filing under the FDA's Commissioner's National Priority Voucher programme, the fastest approval of a new molecular entity since 2002.
This site exists because peptides are difficult: they must be injected, they degrade, they need reconstituting, they are expensive to make, and the gap between what a licensed product costs and what a vial costs is what sustains the entire research-chemical market documented here.
Orforglipron is what happens when that difficulty is engineered away. A small molecule at the same receptor removes the needle, the cold chain and most of the manufacturing cost. If that class matures, it does more to change the economics of this market than any regulatory decision on this site — and it is worth watching for that reason rather than for its weight-loss number.
GLP-1 receptor agonism, by a completely different kind of molecule. The GLP-1 receptor is a class B G-protein-coupled receptor, and class B receptors have large extracellular domains evolved to bind peptide hormones. They were long considered poor targets for small molecules for exactly that reason — there is no obvious small pocket to occupy.
Orforglipron binds an allosteric site rather than reproducing the peptide's binding mode, activating the receptor through a different route to the same downstream signalling: glucose- dependent insulin secretion, glucagon suppression, slowed gastric emptying and central appetite suppression. Solving that binding problem is the actual scientific achievement here.
Oral bioavailability without tricks. Oral semaglutide requires the absorption enhancer SNAC, fasting administration and a strict water limit, and its absorption is still variable. A small molecule is absorbed the way small molecules are absorbed — which is why the label carries no food or fluid restriction and why the timing is flexible.
No cold chain, no reconstitution, no injection. Not pharmacology, but the properties that determine whether a drug reaches people at scale.
Effects that have been reported. A study-tier entry means a result was published — not that the effect is established, reproducible, or transferable from a rodent to a person.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Phase 3 in 3,127 adults with obesity or overweight and a weight-related condition, without diabetes. Dose-dependent mean weight reduction of 7.5% to 11.2% against 2.1% on placebo, alongside improvements in waist circumference, blood pressure and lipids. This is the trial the approval rests on.
Phase 3 in 1,613 adults with type 2 diabetes. Weight reduction of 5.1% to 9.6% against 2.5% on placebo, with significant improvements across pre-specified cardiometabolic endpoints including HbA1c. As across this class, weight loss is smaller in type 2 diabetes than in obesity alone.
The genuine differentiator. Oral semaglutide must be taken fasting, with no more than a small sip of water, at least 30 minutes before food, drink or other oral medicines — and absorption remains variable. Orforglipron has none of those constraints, which matters more for real-world adherence than a percentage point of weight loss.
Peptide manufacturing is a genuine global bottleneck — it is why shortages happened and why compounded copies filled the gap. A small molecule is made by conventional organic synthesis, without the capacity constraints or the cold chain. This is the property with the largest downstream consequences and it is not a clinical endpoint.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
The research-chemical market for incretins exists largely because licensed products are expensive and were, for a period, unavailable. A cheap, oral, non-refrigerated alternative attacks both conditions at once. Whether pricing follows manufacturing cost is a commercial question rather than a scientific one, and it has not been answered yet.
If a class B GPCR evolved to bind a peptide can be activated by a small molecule, the same may be true of other targets in this library — GIP, glucagon, amylin, GHRH. Small-molecule programmes exist across several. That would be a larger change to this field than any individual compound.
Oral dual and triple agonists are the obvious next step, and several are in development. Nothing has reported at the level required to say anything useful.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Early reporting emphasises not injecting rather than the amount of weight lost — consistent with a drug whose effect size sits below the injectables.
A small molecule sold as a cheap tablet has nothing to offer a market built on the cost and scarcity of injectable peptides. This is the first compound in this library where the honest expectation is that no research-chemical version will appear.
Adverse effects, contraindications and unknowns. The grey-market tier is where under-reporting is worst: uncontrolled use produces no systematic safety surveillance at all, so absence of a reported harm is not evidence of safety.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Nausea in 28.9–35.9% against 10.4% on placebo in ATTAIN-1. Vomiting was dose-ordered at 13%, 21% and 24% across the 5.5, 9 and 17.2 mg doses against 4% on placebo. Constipation, diarrhoea and dyspepsia follow. Being a small molecule changes the route, not the receptor — the gastrointestinal profile is a GLP-1 profile.
Dose-ordered at 3%, 6% and 6% across the three doses against 0.7% on placebo. Discontinuation for any adverse event ran from about 5% at the lowest dose to about 10% at the highest, against 2.7% on placebo — lower than retatrutide at its top dose, consistent with a smaller effect size.
Carried across from the GLP-1 class, and contraindicated in personal or family history of medullary thyroid carcinoma or MEN 2. The nuance is worth knowing: orforglipron is not pharmacologically active at the rodent GLP-1 receptor and did not produce tumours in rodents. The warning reflects the unresolved human relevance of a rodent class finding rather than a finding for this molecule. That is a more honest reading than either dismissing the warning or treating it as compound-specific evidence.
Pancreatitis, gallbladder disease, acute kidney injury secondary to dehydration, diabetic retinopathy complications with rapid glycaemic change, hypoglycaemia when combined with insulin or a sulfonylurea, and delayed gastric emptying relevant to any planned procedure requiring sedation.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Well characterised across this class and no reason to expect otherwise here. Benefit is contingent on continuation.
Delayed gastric emptying affects the absorption of narrow-therapeutic-index drugs. Levothyroxine is the recurring example across this library.
The receptor is familiar; this specific molecule is new, and small molecules can have off-target effects that peptides do not. Post-marketing surveillance is where that gets characterised, and it has barely begun.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
The dominant early complaint, as across the class.
A daily oral with a short half-life is more forgiving of a missed dose than a weekly depot injection.
Figures below are documented, not recommended. Study ranges come from published protocols in the stated model; grey-market ranges are what the research community reports using and carry no safety validation of any kind.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
The approved schedule steps 0.8 → 2.5 → 5.5 → 9 → 14.5 → 17.2 mg, advancing every 30 days. Slow escalation is what keeps the gastrointestinal events tolerable, and the discontinuation figures on this page were produced with it.
No fasting requirement, no water restriction, no timing relative to other oral medicines. The most practically significant sentence on the label.
| Step | Dose | Interval | Note |
|---|---|---|---|
| 1 | 0.8 mg | 30 days | Initiation |
| 2 | 2.5 mg | 30 days | |
| 3 | 5.5 mg | 30 days | Lowest dose studied in ATTAIN-1 |
| 4 | 9 mg | 30 days | |
| 5 | 14.5 mg | 30 days | |
| 6 | 17.2 mg | — | Maximum |
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Adverse events and discontinuation are dose-ordered while the weight difference between doses is modest — the same argument that applies across this class.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
This is a prescription tablet with no research-chemical equivalent. There is nothing to reconstitute, nothing to calculate, and no grey-market supply to document.
Combination effects. Almost no peptide combination has been studied as a combination in humans; stack logic is overwhelmingly mechanistic inference and community practice. Each linked compound has its own page.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Glucose-dependence limits intrinsic risk; adding insulin or a sulfonylurea removes that protection and requires the background agent to be reduced. The same rule that applies to every compound in this class.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Same receptor, additive adverse effects, no additional mechanism. That includes combining it with injectable semaglutide or tirzepatide, which is a thing people will try because one is a tablet.
Against oral semaglutide 25 mg, which reported 16.6% weight loss: orforglipron loses on effect size and wins on convenience, cost of manufacture and dosing flexibility. Against the injectables it loses by more on effect and wins by more on everything else. There is no version of this where it is the most potent option.
A meaningful fraction of incretin-driven weight loss is lean tissue, and nothing about the route changes that.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Discussed on convenience grounds. Anyone doing so should expect less weight loss, not more, and the titration restarts from the bottom.
Whole schedules — dosing, titration, cycle length, and off-time — as documented in trials, as proposed from mechanism, and as circulated in the research community. Reproduced for study and comparison only.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Randomised, double-blind, placebo-controlled, 72 weeks, with separate trials in obesity without diabetes and in type 2 diabetes, against dose-ranging arms and pre-specified cardiometabolic endpoints.
Six-step escalation at 30-day intervals, with contraindication screening for medullary thyroid carcinoma and MEN 2 before starting.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Weight regain on discontinuation is the class pattern. A drug that is easy to start and stop invites intermittent use, which is the use least likely to produce the trial result.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
The case for this compound rests on people actually taking it. Early reporting suggests the absence of injection and timing rules is what drives that, which is exactly what the label was designed around.
The approved indication is covered above. This section covers where the class is being looked at beyond it, and how much of that evidence belongs to this molecule rather than to its injectable relatives.
Approved for chronic weight management only. Every other use below is class inference. Orforglipron is new, and the phase 3 programme that supported approval was about weight, not about anything on this list.
Pathophysiology
Nicotine dependence is maintained by mesolimbic dopamine signalling. Quitting also produces an average weight gain of several kilograms, and fear of that gain is a measured barrier to attempting cessation and a measured cause of relapse.
Mechanistic rationale
The randomised evidence in this class is two small trials. Dulaglutide alongside varenicline did not improve abstinence — 63% against 65% — but prevented post-cessation weight gain, −4.6 kg against +0.5 kg. Exenatide alongside a nicotine patch did improve abstinence, 46.3% against 26.8%. Semaglutide has a large observational signal whose own investigators said it does not justify off-label use. Nothing has been tested for this agent, and in every trial the GLP-1 was added to a treatment that already works rather than replacing it.
Community reports
The consistent finding across the randomised literature is the weight, not the quitting. Post-cessation weight gain is real, specific and worth addressing; improved abstinence is not established, and the whole randomised evidence base is roughly 410 participants.
Components carrying the argument: GLP-1 receptor — class inference only
| Question | Position |
|---|---|
| Approved for | Chronic weight management, adults |
| Smoking cessation evidence for this agent | None |
| Class evidence | Two small RCTs, ~410 participants, divergent on abstinence |
| Consistent class finding | Prevention of post-cessation weight gain |
| In every trial | Added to varenicline or a nicotine patch, never alone |
For smoking cessation: varenicline has the largest effect size of any single agent, followed by combination nicotine replacement — a patch plus a fast-acting form — and bupropion. Behavioural support roughly doubles the odds of success on top of any of them, and cytisinicline is an option where varenicline is unavailable. Nothing in this drug class approaches those effect sizes, and no trial has tested a GLP-1 as a substitute for any of them.
For obesity: an energy deficit that can be maintained, resistance training to protect lean mass, sleep, and treatment of undiagnosed obstructive sleep apnoea. Bariatric surgery still produces the largest and most durable results.
Physical-chemistry reference for laboratory handling of the lyophilised material. Reproduced so that stability and concentration mathematics can be studied — see the calculator for the arithmetic and the reconstitution guide for sterile technique.
None. It is a film-coated tablet. There is no lyophilised form, no diluent, no sterile technique and nothing for the calculator to compute — which is itself the point of this page.
Room temperature, in the original container. No refrigeration and no cold chain, which is the property that most distinguishes it from every injectable in this library and the one with the largest consequences for global access.
Not applicable. Supplied as tablets across the six titration strengths.
A small molecule in a tablet has a shelf life measured in years and tolerates ordinary shipping and storage. Peptides do not.
Regulatory status changes and differs by country. This is a summary for orientation, not legal advice — check your own jurisdiction.
Approved prescription medicine. Approved by the FDA on 1 April 2026 as Foundayo, in combination with a reduced-calorie diet and increased physical activity, to reduce excess body weight and maintain weight reduction in adults with obesity, or with overweight and at least one weight-related comorbid condition.
Notable for the route as well as the result: it was the fifth approval under the FDA Commissioner's National Priority Voucher pilot, issued 50 days after filing — the fastest approval of a new molecular entity since 2002.
Carries a boxed warning for thyroid C-cell tumours and is contraindicated in personal or family history of medullary thyroid carcinoma or MEN 2. See the adverse effects section for why that warning is a class carry-over rather than a finding for this molecule.
Regulatory and trial claims re-checked against primary sources on 16 August 2026. Checked: FDA approval 1 April 2026; ATTAIN-1 and -2; label and boxed warning. Approvals, trial readouts and compounding decisions move faster than anything else on this page — a date here means someone looked, not that nothing has changed since.
Metabolic modulators are addressed under the WADA Prohibited List. Verify against the current list.
Links resolve to PubMed records, trial registries, publisher pages or primary documents. Where a body of work rather than a single paper is cited, the link opens a PubMed query so the full result set — including newer papers than this page — can be reviewed. Verify every claim against the primary source before relying on it.
For educational and research reference only. Nothing on this site is medical advice, a recommendation, or an instruction to administer any substance to a human being. Every figure on this page is a record of what has been reported, not a recommendation. Full disclaimer.
