What the human research shows
The trade the whole obesity field is watching: less weight loss than the injections, in a pill that anyone can take anywhere. The evidence is unusually strong for something this new because Lilly published the full phase 3 programme rather than announcing it.
Evidence profile0–5
- Metabolic & weightA5.0
- CardiovascularB0.0
- Muscle & growth—0.0
- Healing & repair—0.0
- Neuro & sleep—0.0
- Immune & inflammation—0.0
- Sexual & hormonal—0.0
- Skin & appearance—0.0
- Ageing & longevity—0.0
| Outcome | Grade | Effect size | Human studies | Where the evidence comes from |
|---|---|---|---|---|
| Body weight | AEstablished | Moderate | Phase 3 RCT (n=3,127) + programme | ATTAIN-1, 72 weeks in adults with obesity and no diabetes: −11.2% on the 36 mg dose versus −2.1% on placebo. 36.0% lost at least 15% of body weight, against 5.9% on placebo.1 |
| Blood glucose (HbA1c) | AEstablished | Large | Phase 3 RCT (n=559) + programme | ACHIEVE-1, 40 weeks in type 2 diabetes managed by diet and exercise alone: HbA1c fell 1.24–1.48 points versus 0.41 on placebo, bringing the average to 6.5–6.7%.2 |
| Major cardiovascular events | BProbable | Not measurable | 1 phase 3 safety RCT (ACHIEVE-4, n=2,749, median 2 yr) | ACHIEVE-4, published in The Lancet on 30 September 2026: adults with type 2 diabetes, overweight or obesity and established cardiovascular or chronic kidney disease took orforglipron or insulin glargine, open label. A major cardiovascular event occurred in 4.2% on orforglipron and 5.0% on glargine (hazard ratio 0.84, 95% CI 0.59–1.20). That meets non-inferiority, so cardiovascular safety is confirmed; the interval crosses 1, so a reduction in events is not shown. Deaths were 1.4% against 3.2%, in a trial built to test safety, not that difference. Clinically significant hypoglycaemia: 6.8% vs 19.2%.5 |
| GI side effectsadverse | AEstablished | Moderate | Phase 3 programme | The familiar incretin profile. In ATTAIN-1, adverse events caused 5.3–10.3% of participants to stop, against 2.7% on placebo. In ACHIEVE-4, gastrointestinal events were reported in 62.1% on orforglipron against 14.2% on insulin glargine.15 |
Literature searched to 7 October 2026. Human studies only; animal and cell work informs the mechanism section and nothing else.
Registered trials
ClinicalTrials.gov lists 52 interventional studies naming Orforglipron as an intervention — 32 completed, 8 recruiting, and 27 with results posted to the registry.
A registration is not a result. Anyone can register a study, and many never report — so this list shows what has been attempted, not what has been shown. The graded evidence above is the answer to whether something works.
44 further studies are registered. Participant counts marked * are the sponsor's estimate, not a final enrolment. Source: ClinicalTrials.gov, read directly from the registry and refreshed weekly.
What it is
Orforglipron does the same job as semaglutide at the same receptor, but it is a small synthetic molecule rather than a peptide. That distinction is the entire point: peptides are digested, which is why GLP-1 drugs are normally injected, and why the one oral peptide version needs a special absorption enhancer and an empty stomach.
It is included here because it competes directly with the peptides on this site and because the search traffic treats it as one. It is not a peptide.
How it is thought to work
It binds and activates the GLP-1 receptor, producing the same downstream effects as the injectables: more insulin when glucose is high, slower gastric emptying, reduced appetite. Being a small molecule, it can be manufactured by chemical synthesis rather than biological production — the reason it is expected to be cheaper and easier to supply at scale than any injected GLP-1.
What is still unknown
- Whether it prevents cardiovascular events: ACHIEVE-4 confirmed safety against insulin glargine but did not show a reduction, and there is no placebo-controlled outcomes trial.
- How much of the weight loss is kept after stopping, as with every drug in this class.
- Long-term safety beyond the phase 3 window.
The molecule and how long it lasts
- Formula
- C48H48F2N10O5
- Molecular weight
- 883.0 g/mol
- CAS number
- 2212020-52-3
- PubChem
- CID 137319706
PubChem record, read 23 September 2026.
- Route
- Oral tablet, once daily
- Half-life
- About 29-49 hours
- Licensed regimen (Foundayo)
- 0.8 mg daily, then after ≥30 days 2.5 mg, then 5.5 mg, then 9, 14.5 or 17.2 mg daily with ≥30 days between escalations; maximum 17.2 mg daily
From the approved product's prescribing information: Foundayo prescribing information (DailyMed) The regimen is the label's own wording, reproduced as a regulatory fact.
Regulatory status
No EMA marketing authorisation. Under regulatory review following the phase 3 programme.
Foundayo approved by the FDA on 1 April 2026 to reduce excess body weight and maintain weight reduction in adults with obesity, or with overweight and at least one weight-related condition. Anything sold as orforglipron without a prescription is not the licensed product.
No MHRA licence.
Investigational only.
No Drug Identification Number.
GLP-1 receptor agonists are not on the 2026 Prohibited List.
Questions people actually ask
Is orforglipron as good as Ozempic or Mounjaro?
Is orforglipron a peptide?
Can I buy it?
One page per claimed effect
- ADoes Orforglipron help with body weight?Phase 3 RCT (n=3,127) + programme
- ADoes Orforglipron help with blood glucose?Phase 3 RCT (n=559) + programme
- BDoes Orforglipron help with major cardiovascular events?1 phase 3 safety RCT (ACHIEVE-4, n=2,749, median 2 yr)
- AHow common is GI side effects with Orforglipron?Phase 3 programme
References
- 1Wharton S, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1).N Engl J Med, 2025;393:1796–18063,127 adults, 72 weeks.
- 2Rosenstock J, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist, in early type 2 diabetes (ACHIEVE-1).N Engl J Med, 2025;393:1065–1076559 participants, 40 weeks.
- 3
- 4Wharton S, et al. Hepatic safety of orforglipron: a pooled analysis of the phase 3 clinical trials.Diabetes Obes Metab, 2026
- 5Klein KR, et al. 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 (online 30 Sep)2,749 randomised, 317 sites, median follow-up 2 years; MACE-4 hazard ratio 0.84 (95% CI 0.59–1.20), non-inferiority margin 1.8. NCT05803421.
- 6FDA. Novel Drug Approvals for 2026 (Foundayo, orforglipron, approved 1 April 2026).FDA, read 7 Oct 2026Approved use on the approval date: chronic weight management in adults with obesity, or overweight with a weight-related condition.
Change log
- 2026-10-07ACHIEVE-4 (Lancet, 30 Sep 2026) added as a cardiovascular row: safety confirmed against insulin glargine, no reduction in events shown, graded B at effect 0. Status corrected to approved in the United States (Foundayo, FDA, 1 April 2026), which this page had not yet recorded. Other grades unchanged.
- 2026-09-03Initial publication from the published phase 3 programme (ATTAIN-1, ACHIEVE-1, ATTAIN-2).