Orforglipron (LY3502970) — what it does, evidence, and safety

What it is

Orforglipron is best known as the first GLP-1 pill for weight loss — sold as Foundayo, it's a once-daily tablet that works the same way as injectable GLP-1 drugs, increasing fullness and helping control blood sugar, but as a small, non-peptide molecule it survives digestion without the food or water timing rules oral semaglutide requires. The FDA approved it for chronic weight management on April 1, 2026. It has also been studied in adults with type 2 diabetes, but that use is not yet FDA-approved.

What the research found

Orforglipron is an oral (non-injected) GLP-1 pill studied for obesity and type 2 diabetes. In the Phase 3 ATTAIN-1 obesity trial, once-daily orforglipron was associated with average weight reductions of about 7.5%, 8.4%, and 11.2% at 72 weeks versus about 2.1% on placebo, and in ATTAIN-2 (obesity with type 2 diabetes) the dose reached about 9.6% alongside HbA1c improvements. A separate Phase 3 diabetes program (ACHIEVE) reported HbA1c reductions versus placebo and several comparators. Gastrointestinal effects (nausea, diarrhea) were the most common side effects, mostly mild to moderate. The research attributes these weight and blood-sugar changes largely to reduced appetite and food intake (greater satiety via the gut-hormone pathway these agents act on), an appetite and energy-intake mechanism measured across the trials.

Status and regulatory position

FDA-approved (Foundayo, April 1, 2026, NDA 220934) for chronic weight management only; the type 2 diabetes indication is not FDA-approved (a T2D regulatory filing is underway as of July 2026) although the phase 3 ACHIEVE program in T2D is published. WADA: not specifically named on the Prohibited List (GLP-1 receptor agonists are not prohibited); now an approved drug. Not DEA-scheduled.

Safety

Orforglipron is FDA-approved as Foundayo for chronic weight management; it is a prescription medication, not a research-only compound. As a GLP-1 receptor agonist it carries the class boxed warning about thyroid C-cell tumors and is contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN2. The most commonly reported effects in trials were gastrointestinal. As an approved drug, orforglipron is not specifically named on the WADA Prohibited List (GLP-1 receptor agonists are not prohibited). VialWise is a research and educational reference, not medical advice — consult a licensed professional.

Disclosures

⚠️ For research and educational purposes only. Orforglipron is an FDA-approved prescription medication (Foundayo). Information in this entry is informational, not medical advice. Always confirm any dose figures with the in-app calculator and consult appropriate professional guidance before any decisions.

⚠️ This is an oral tablet — there is no reconstitution. Orforglipron is a swallowed pill, not an injectable peptide. The reconstitution and syringe-draw workflow used elsewhere in this library does not apply. Dose figures below are reported from published trials and the approved product, not protocol recommendations.

Quick reference

Form	Oral tablet (small-molecule, non-peptide) — no reconstitution
Approved tablet strengths	Foundayo is supplied as and tablets — not the trial dose numbers; the tablet is reported as bioequivalent to the trial dose[³][¹⁵]
Frequency	Once daily, oral
Food/water restrictions	None — can be taken any time of day without food or water timing restrictions[³][⁴]
Half-life	~25–35 hours after a single dose; ~48–68 hours at steady state (Day 28)[⁵]
Oral bioavailability	~79% (reported in a 2025 review)[⁴]
Route	Oral
Regulatory status	FDA-approved April 1, 2026 as Foundayo for chronic weight management only; type 2 diabetes is not an approved indication (filing underway as of July 2026)[⁶]

In depth

Orforglipron (development code LY3502970, brand name Foundayo) is an oral, small-molecule, non-peptide GLP-1 receptor agonist developed by Eli Lilly. Its defining feature is that it is a small chemical molecule rather than a peptide, so it survives digestion well enough to be taken as a once-daily tablet — and, unlike oral semaglutide (which requires fasting and specific water/timing rules), it can be taken any time of day without food or water restrictions.[³][⁴] A 2025 review reported oral bioavailability of approximately 79%.[⁴]

The U.S. FDA approved orforglipron as Foundayo on April 1, 2026 for chronic weight management in adults with obesity, or overweight with at least one weight-related condition, as an adjunct to a reduced-calorie diet and increased physical activity.[⁶] This makes it the first oral small-molecule GLP-1 receptor agonist approved for weight management. Weight management is the only approved indication — type 2 diabetes is not an FDA-approved use of orforglipron as of July 2026, although the Phase 3 ACHIEVE program in T2D is published and a regulatory filing for that indication is underway.[³][⁶] Note for the VialWise audience: although orforglipron is now an approved prescription drug, it appears in this library because it is a heavily-discussed metabolic compound; this entry is educational reference, not a sourcing or self-administration guide.

A note on dose numbers. The / / / figures reported throughout the trial literature are *trial doses*, not the strengths of the approved product. Foundayo is supplied as and tablets.[³] A 2026 network meta-analysis reported that the commercial tablet is bioequivalent to the dose used in the trials.[¹⁵] Trial dose numbers and label strengths should not be used interchangeably.

Phase 3 efficacy. According to PubMed, the Phase 3 ATTAIN-1 obesity trial (Wharton et al., NEJM 2025; NCT05869903, n=3127, adults with obesity without diabetes) reported mean body-weight change from baseline to week 72 of −7.5%, −8.4%, and −11.2%, versus −2.1% with placebo.[¹] In the group, 54.6% achieved ≥10% weight reduction, 36.0% achieved ≥15%, and 18.4% achieved ≥20%.[¹] A separate Phase 3 trial in adults with obesity and type 2 diabetes (ATTAIN-2; Horn et al., Lancet 2025; NCT05872620, n=1613) reported mean weight change of −5.1%, −7.0%, and −9.6% versus −2.5% with placebo at 72 weeks, alongside statistically significant HbA1c improvements.[²]

Phase 3 type 2 diabetes program (ACHIEVE). Orforglipron's T2D evidence base is the ACHIEVE program, now published as primary trial reports. In ACHIEVE-1 (Rosenstock et al., NEJM 2025; NCT05971940), a placebo-controlled trial in early type 2 diabetes, participants taking once-daily orforglipron had 40-week HbA1c changes of −1.24, −1.47 and −1.48 percentage points versus −0.41 with placebo, with body-weight changes of −4.5%, −5.8% and −7.6% versus −1.7%.[¹⁰] In ACHIEVE-2 (Welch et al., Lancet 2026; NCT06192108), an open-label non-inferiority trial versus dapagliflozin, 40-week HbA1c changes were −1.23%, −1.50% and −1.56% versus −0.81% with dapagliflozin.[¹¹] In ACHIEVE-3 (Rosenstock et al., Lancet 2026; NCT06045221), an open-label non-inferiority trial versus oral semaglutide, 52-week HbA1c change on the treatment-regimen estimand was −1.71% and −1.91% for orforglipron versus −1.23% and −1.47% for oral semaglutide; orforglipron met non-inferiority and was reported as superior to both semaglutide doses on HbA1c, while gastrointestinal events and pulse-rate increase were more frequent with orforglipron.[¹²] In ACHIEVE-5 (Giorgino et al., JAMA 2026; NCT06109311), orforglipron added to titrated insulin glargine produced 40-week HbA1c changes of −1.58%, −1.88% and −1.82% versus −0.79% with placebo, without an increase in clinically significant hypoglycemia.[¹³] These are trial-reported outcomes in enrolled study populations, not expected individual results.

Mechanism nuance. A 2025 review reported that orforglipron stimulates cyclic AMP without strong β-arrestin recruitment, which the authors suggested may limit receptor desensitization.[⁷]

Reported side effects

Commonly reported

Nausea
Diarrhea
Vomiting
Constipation
Decreased appetite
Mild-to-moderate gastrointestinal effects, predominantly during dose escalation[¹][²]

Serious

A small number of mild pancreatitis cases were reported with orforglipron in the Phase 3 program[⁹]
Non-dose-dependent heart-rate increase reported in review of the program[⁷]
Thyroid C-cell tumor risk — the approved Foundayo label carries a boxed warning about thyroid C-cell tumors, consistent with the GLP-1 receptor agonist class[⁶]
Gallbladder-related symptoms (class effect across incretins)

Contraindications and warnings

Boxed warning — thyroid C-cell tumors. The FDA-approved Foundayo label carries a boxed warning regarding the risk of thyroid C-cell tumors, in line with the GLP-1 receptor agonist class.[⁶]

Contraindicated in people with a personal or family history of medullary thyroid carcinoma (MTC) or in those with Multiple Endocrine Neoplasia syndrome type 2 (MEN2).[⁶]

History of pancreatitis

Severe gastrointestinal disease

Concurrent use of other GLP-1 / incretin agonists

Pregnancy and lactation — discuss with a clinician; weight-management drugs of this class are generally not used in pregnancy

Key terms

GLP-1 receptor agonist: A compound that switches on the GLP-1 receptor, the same target a natural gut hormone uses to signal fullness and help regulate blood sugar.
Small molecule / non-peptide: A drug built from a small chemical structure rather than a chain of amino acids (a peptide). Small molecules can often survive digestion, which is what allows orforglipron to work as a swallowed pill.
Oral bioavailability: The fraction of a swallowed dose that actually reaches the bloodstream. Higher oral bioavailability means more of a pill is absorbed.
Half-life: Roughly how long the body takes to clear half of a dose. A long enough half-life is why some compounds can be taken just once a day.
Titration: Gradually increasing a dose over weeks, which research with this class uses to reduce stomach-related side effects.

Sources

Related entries

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CagriSema — same mechanism class
Dulaglutide — same mechanism class
Exenatide — same mechanism class
Liraglutide — same mechanism class
Mazdutide — same mechanism class