Reviewed & approved by Dr. Nova Reyes · Last checked 2026-10-25. ← Back to Evidence Library

Orforglipron: what the evidence says

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

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About the evidence

Orforglipron is not a peptide, so it is an unusual fit for this Library. We include it because it competes directly with the GLP-1 peptides people are buying. Nearly every trial was designed, funded and partly written by Eli Lilly. "Treatment-regimen" results count everyone, whether or not they kept taking the drug, which gives a more realistic picture.

Where it's approved

• US: FDA approved Foundayo on April 1, 2026 as a new molecular entity, for weight reduction and long-term weight maintenance with diet and exercise in adults with obesity, or overweight plus at least one weight-related condition. The label says not to combine it with another GLP-1 drug. ^{R13, R14}
• Elsewhere: a review article says it has been submitted in the EU (weight and type 2 diabetes), Japan (weight) and Canada (type 2 diabetes). ^R12 [UNVERIFIED: not checked against EMA, PMDA or Health Canada.]

The approved medicine: what its trials showed

• Human Obesity without diabetes (ATTAIN-1, phase 3): in 3,127 adults, average weight change was −7.5%, −8.4% and −11.2% on the three orforglipron arms vs −2.1% on placebo (treatment-regimen). On the highest arm, 54.6% lost at least 10% of their weight vs 12.9% on placebo. Waist size, blood pressure and some blood fats also improved. ^R1
• Human Obesity with type 2 diabetes (ATTAIN-2, phase 3): in 1,613 adults, weight change was −5.1% to −9.6% vs −2.5% on placebo. People with diabetes usually lose less weight on these drugs. ^R2
• Human Keeping weight off after injections (ATTAIN-MAINTAIN): in 376 people who had already lost weight on tirzepatide or semaglutide, those switched to orforglipron kept more of their lost weight than those switched to placebo (about 75% to 79% kept vs 38% to 49%). The trial did not include a group that stayed on the injections. ^R7
• Human Earlier phase 2 trial: in 272 adults with obesity, weight change ranged from −9.4% to −14.7% vs −2.3% on placebo. ^R10
• Unknown How it compares head-to-head with injectable semaglutide or tirzepatide for weight.

Does it help type 2 diabetes?

Not an FDA-approved use as of Oct 24, 2026. ^R13

• Human Early diabetes on diet and exercise (ACHIEVE-1, phase 3): in 559 adults, HbA1c (average blood sugar) fell 1.24 to 1.48 points vs 0.41 on placebo, and weight fell 4.5% to 7.6% vs 1.7%. No severe low blood sugar was reported. ^R3
• Human Versus oral semaglutide (ACHIEVE-3, phase 3, open-label): in 1,698 adults on metformin, HbA1c fell 1.71 and 1.91 points vs 1.23 and 1.47 on oral semaglutide, and both orforglipron arms beat both semaglutide arms. Stomach side effects (58% to 59% vs 37% to 45%) and stopping for side effects (9% to 10% vs 4% to 5%) were more common on orforglipron. ^R4
• Human Versus dapagliflozin (ACHIEVE-2, phase 3, open-label): in 962 adults on metformin, HbA1c fell 1.23 to 1.56 points vs 0.81 on dapagliflozin. ^R5
• Human Added to insulin glargine (ACHIEVE-5): in 546 adults, HbA1c fell 1.58 to 1.88 points vs 0.79 on placebo, without more clinically significant low blood sugar. ^R6
• Human Earlier phase 2 trial: in 383 adults with type 2 diabetes, HbA1c fell by up to 2.10 points on orforglipron vs 0.43 on placebo and 1.10 on dulaglutide (Trulicity), and weight fell by up to 10.1 kg vs 2.2 kg on placebo and 3.9 kg on dulaglutide. ^R11
• Human Heart safety (ACHIEVE-4, phase 3, open-label): in 2,749 adults with diabetes at high heart risk, major heart events occurred in 4.2% on orforglipron vs 5.0% on insulin glargine, which met the goal of showing it was not worse. Low blood sugar was less common on orforglipron (6.8% vs 19.2%). ^R8

Is it safe?

The FDA label is the most complete safety source. ^R14

• Caution Boxed warning (thyroid C-cell tumors): this is the class warning for GLP-1 drugs. The label notes orforglipron does not act in rats or mice and caused no tumors in rodents, but its relevance to humans is not determined. People with a personal or family history of medullary thyroid cancer or MEN 2 (multiple endocrine neoplasia type 2, a rare inherited tumor syndrome) should not take it. ^R14
• Caution Label warnings: pancreatitis, severe stomach reactions (not recommended with severe gastroparesis, or delayed stomach emptying), kidney injury from dehydration, low blood sugar with insulin or sulfonylureas (older blood-sugar-lowering pills), serious allergic reactions, worsening diabetic eye disease, gallbladder disease, and inhaling stomach contents during anesthesia. ^R14
• Caution Stomach side effects were the most common problem in every trial and caused more people to stop than placebo (5.3% to 10.3% vs 2.7% in ATTAIN-1). ^R1
• Caution Heart rate: pulse rose a few beats per minute more than on oral semaglutide. ^R4
• Caution Drug interactions: it can lower how well birth-control pills work, so the label advises a non-pill or backup method around starting and increasing treatment. Some other medicines change its blood levels; check the label with a pharmacist. ^R14
• Human Liver: a pooled look at seven phase 3 trials (11,220 people) found no sign of drug-induced liver injury. ^R9
• Unknown Long-term safety beyond a few years and rare harms.

Compounded and gray-market orforglipron: extra risks

• Caution Use the real product. Because Foundayo is an FDA-approved pill, there is no medical reason to use an unapproved "research" version. Unknown We have not found published lab tests of gray-market orforglipron.
• Caution Don't stack with other GLP-1 drugs. The label says not to combine it with another GLP-1 drug. ^R14
• Caution Pill strengths in trials and on the label differ (see Study details). Don't assume a trial arm matches a product strength. Unknown The reason is not stated in the abstracts we reviewed.

What we don't know

• Unknown Whether it lowers heart attacks and strokes in people with obesity (a heart-outcomes trial is recruiting) ^R15
• Unknown Head-to-head results against injectable semaglutide or tirzepatide
• Unknown Long-term safety, and whether weight comes back after stopping
• Unknown Whether and when it will be approved for type 2 diabetes in the US

Is it legal?

FDA-approved as Foundayo (NDA 220934) for chronic weight management in adults, approved April 1, 2026, prescription only; label revised July 2026. ^{R13, R14} Checked on Drugs@FDA and openFDA, Oct 24, 2026. Using it for type 2 diabetes would be off-label in the US. EU, Japan, Canada: submissions reported [UNVERIFIED: not checked against EMA, PMDA or Health Canada]. China: UNVERIFIED not checked against NMPA. WADA: not named on the 2026 Prohibited List, and S0 covers only substances with no current approval anywhere ^R17. As of Oct 24, 2026.

What's in the vial?

Real orforglipron is a tablet sold by prescription under the name Foundayo. ^R13 It is not supplied in vials. We have not found published lab tests of gray-market orforglipron powders or capsules. See results at /tests/. A passing test covers one batch, tested on one date. It does not mean the compound itself is safe.

What do users report?

Self-report, not evidence.

Unknown TBD. We'll only list this once we can cite a public source.

Study details

These are doses researchers used, not recommendations. All trials sponsored by Eli Lilly (ClinicalTrials.gov records; funding statement quoted in ATTAIN-1). All arms oral, once daily. Trial doses (up to 36 mg, plus 45 mg in phase 2) differ from the FDA label strengths (0.8 to 17.2 mg, stated as base); the abstracts reviewed do not explain the difference (possibly formulation or salt form, Unknown).

R1, R2, R7, R10 Human: Weight trials (ATTAIN)

Study	People	Route	Dose used	Follow-up	Reported	Side effects / dropouts	Citation
ATTAIN-1 (Wharton 2025), obesity, no diabetes, NCT05869903	3,127 (3:3:3:4)	Oral	6, 12 or 36 mg once daily vs placebo	72 wk	−7.5%, −8.4%, −11.2% vs −2.1% (treatment-regimen); 36 mg: ≥10% loss 54.6% vs 12.9%	Stopped for AEs 5.3–10.3% vs 2.7%; mostly GI	PMID 40960239
ATTAIN-2 (Horn 2026), obesity + T2D, NCT05872620	1,613 (329/332/322 vs 630)	Oral	6, 12 or 36 mg once daily vs placebo	72 wk	−5.1%, −7.0%, −9.6% vs −2.5%	Stopped for AEs 6.1–9.9% vs 4.1%; 10 deaths (6 vs 4), 1 per arm possibly related	PMID 41275875
ATTAIN-MAINTAIN (Aronne 2026), after SURMOUNT-5, NCT06584916	376 (205 ex-tirzepatide, 171 ex-semaglutide)	Oral	Orforglipron once daily vs placebo	52 wk	Weight loss kept: 74.7% vs 49.2% (ex-tirzepatide); 79.3% vs 37.6% (ex-semaglutide)	Mostly GI; no continued-injection arm	PMID 42120723
Phase 2 obesity (Wharton 2023)	272	Oral	12, 24, 36 or 45 mg once daily vs placebo	36 wk	−9.4% to −14.7% vs −2.3%	GI-related stopping 10–17%	PMID 37351564

R3–R6, R8, R11 Human: Type 2 diabetes trials (ACHIEVE)

Study	People	Route	Dose used	Follow-up	Reported	Side effects / dropouts	Citation
ACHIEVE-1 (Rosenstock 2025), diet/exercise only	559	Oral	3, 12 or 36 mg once daily vs placebo	40 wk	HbA1c −1.24, −1.47, −1.48 vs −0.41; weight −4.5%, −5.8%, −7.6% vs −1.7%	Stopped for AEs 4.4–7.8% vs 1.4%; no severe hypoglycemia	PMID 40544435
ACHIEVE-3 (Rosenstock 2026), vs oral semaglutide, open-label, NCT06045221	1,698	Oral	12 or 36 mg vs oral semaglutide 7 or 14 mg, once daily	52 wk	HbA1c −1.71, −1.91 vs −1.23, −1.47; superiority met	GI 59%, 58% vs 37%, 45%; stopped for AEs 9%, 10% vs 4%, 5%; pulse +3.7/+4.7 vs +1.0/+1.5 bpm	PMID 41765029
ACHIEVE-2 (Welch 2026), vs dapagliflozin, open-label	962	Oral	3, 12 or 36 mg once daily vs dapagliflozin 10 mg	40 wk	HbA1c −1.23, −1.50, −1.56 vs −0.81	GI 47%, 46%, 54% vs 12%; stopped 15%, 18%, 20% vs 6%	PMID 42259339
ACHIEVE-5 (Giorgino 2026), + insulin glargine	546	Oral	3, 12 or 36 mg once daily vs placebo	40 wk	HbA1c −1.58, −1.88, −1.82 vs −0.79; weight −2.6%, −4.8%, −5.4% vs +0.2%	No increase in clinically significant hypoglycemia	PMID 42251769
ACHIEVE-4 (Klein 2026), CV safety vs insulin glargine, open-label	2,749 (1,371 vs 1,378)	Oral	Orforglipron once daily vs insulin glargine	Median 2 years	MACE-4 4.2% vs 5.0% (HR 0.84, 95% CI 0.59–1.20; non-inferiority met)	GI 62.1% vs 14.2%; hypoglycemia 6.8% vs 19.2%; deaths 1.4% vs 3.2%	PMID 42815506
Phase 2 T2D (Frias 2023), NCT05048719	383	Oral	3, 12, 24, 36 or 45 mg once daily vs dulaglutide 1.5 mg weekly vs placebo	26 wk	HbA1c up to −2.10% vs −0.43% placebo and −1.10% dulaglutide; weight up to −10.1 kg vs −2.2 kg placebo and −3.9 kg dulaglutide	GI events 44.1–70.4% vs 18.2% placebo and 34.0% dulaglutide; 3 vs 0 placebo (1 dulaglutide) level 2 hypoglycemia; 0 severe hypoglycemia	PMID 37369232

R9 Human: Pooled liver safety

Wharton 2026: 11,220 people across seven phase 3 trials (6,920 on orforglipron), up to 104 wk. ALT/AST fell on average; 6 (0.1%) vs 6 (0.1%) met lab criteria for possible liver injury, all orforglipron cases with other causes; no Hy's Law cases. PMID 42338042

R12–R15 Regulatory and background (as of Oct 24, 2026)

• R13 Drugs@FDA: FOUNDAYO (orforglipron calcium), NDA 220934, Eli Lilly; original approval April 1, 2026 (Type 1, new molecular entity); labeling supplement 3, Aug 4, 2026. Tablet strengths 0.8, 2.5, 5.5, 9, 14.5 and 17.2 mg (as base). Checked via openFDA Oct 24, 2026.
• R14 FDA label, Foundayo prescribing information, revised 07/2026 (S-003): indication chronic weight management; boxed warning for thyroid C-cell tumors; limitation of use with another GLP-1 receptor agonist; oral contraceptive and CYP3A4 interactions.
• R12 Shirley M, "Orforglipron: First Approval," Drugs 2026 (review; not a regulator): submissions in the EU, Japan and Canada. UNVERIFIED
• R15 ClinicalTrials.gov NCT07241390: cardiovascular outcomes trial in adults with atherosclerotic disease, recruiting (source index, Oct 21, 2026).
• EMA, PMDA, NMPA: UNVERIFIED not checked directly.

Full reference list (all PMIDs verified on PubMed, Oct 24, 2026)

1. Wharton S, et al. N Engl J Med. 2025;393(18):1796-1806. doi:10.1056/NEJMoa2511774. PMID 40960239
2. Horn DB, et al. Lancet. 2026;406(10522):2927-2944. doi:10.1016/S0140-6736(25)02165-8. PMID 41275875
3. Rosenstock J, et al. N Engl J Med. 2025;393(11):1065-1076. doi:10.1056/NEJMoa2505669. PMID 40544435
4. Rosenstock J, et al. Lancet. 2026;407(10534):1147-1160. doi:10.1016/S0140-6736(26)00202-3. PMID 41765029
5. Welch M, et al. Lancet. 2026;408(10550):125-140. doi:10.1016/S0140-6736(26)00800-7. PMID 42259339
6. Giorgino F, et al. JAMA. 2026;336(5):389-399. doi:10.1001/jama.2026.9512. PMID 42251769
7. Aronne LJ, et al. Nat Med. 2026;32(7):2679-2687. doi:10.1038/s41591-026-04386-7. PMID 42120723
8. Klein KR, et al. Lancet. 2026;408(10564):1557-1570. doi:10.1016/S0140-6736(26)01865-9. PMID 42815506
9. Wharton S, et al. Diabetes Obes Metab. 2026;28(9):8347-8358. doi:10.1111/dom.71032. PMID 42338042
10. Wharton S, et al. N Engl J Med. 2023;389(10):877-888. doi:10.1056/NEJMoa2302392. PMID 37351564
11. Frias JP, et al. Lancet. 2023;402(10400):472-483. doi:10.1016/S0140-6736(23)01302-8. PMID 37369232
12. Shirley M. Drugs. 2026;86(10):1735-1745. doi:10.1007/s40265-026-02363-5. PMID 42479349
13. FDA. Drugs@FDA: Foundayo, NDA 220934. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=220934
14. FDA. Foundayo prescribing information (rev. 07/2026). https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220934s003lbl.pdf
15. ClinicalTrials.gov. NCT07241390. https://clinicaltrials.gov/study/NCT07241390
16. WADA. World Anti-Doping Code International Standard: Prohibited List 2026 (in force Jan 1, 2026). https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf (text read Oct 24, 2026)

Disclaimer

This page is for education and harm reduction. It is not medical advice and not a recommendation to use orforglipron outside a prescription. Please talk to a clinician you trust before making medical decisions, seek care right away for severe stomach pain or repeated vomiting, and report problems to FDA MedWatch (https://www.fda.gov/safety/medwatch).