Orforglipron
Orforglipron — the first oral small-molecule GLP-1: evidence & status

Class: small_molecule
Synonyms: orforglipron (or-for-GLIP-ron)
Lilly code LY3502970
Chugai code OWL833
Function tags: metabolic
obesity / weight
type-2 diabetes (investigational)
Overall evidence grade: B
WADA prohibited: no
WADA note: Sport: GLP-1 agonists are not currently on the WADA Prohibited List.
Last updated: 2026-07-13

In brief: Orforglipron is the first oral small-molecule GLP-1 — a non-peptide pill, taken anytime without food/water restrictions, that in Phase 3 delivered semaglutide-level weight loss (~11–12%) and solid glycemic control. Its significance is less about the size of the effect than about manufacturing and access: a cheaply mass-produced oral GLP-1 that Lilly says it can supply worldwide without constraint. Lilly filed the obesity NDA in December 2025; it is not yet approved.

## Identity an investigational, **once-daily small-molecule (non-peptide) oral GLP-1 receptor agonist** — and, critically, one that can be taken **any time of day with no food or water restrictions.** Discovered by **Chugai Pharmaceutical (Japan)** and **licensed by Lilly in 2018**; the two published its preclinical pharmacology together. ## Mechanism (as proposed) a **small-molecule agonist of the GLP-1 receptor** (with biased/partial-agonist pharmacology distinct from the peptide full agonists) → the familiar GLP-1 effects (glucose-dependent insulin, glucagon suppression, slowed gastric emptying, reduced appetite). The novelty is not the target but the **chemistry** — a non-peptide that survives oral dosing without absorption enhancers or a dosing ritual, and that can be manufactured like a conventional tablet.

Evidence grades by outcome:
outcome: Weight loss (obesity)
grade: B
base: Phase 3 ATTAIN-1 (NEJM 2025, ~11–12%); NDA filed Dec 2025
effect: Meaningful; semaglutide-like
caveat: Strong Phase 3 and FDA-filed, but not yet approved; efficacy is semaglutide-level, not tirzepatide-level
outcome: Type-2 diabetes glycemic control
grade: B
base: Phase 3 ACHIEVE programme (5 trials, superior A1C; NEJM 2025)
effect: Robust, foundational
caveat: Phase 3 complete/near-complete; T2D filing 2026; not yet approved
outcome: Weight maintenance after injectables
grade: B
base: ATTAIN-MAINTAIN (Dec 2025)
effect: Maintained (switch from Wegovy/Zepbound)
caveat: First-of-its-kind; topline
outcome: Manufacturing / access advantage
base: Small-molecule chemistry
effect: Cheap, scalable, no cold chain, no food/water ritual
caveat: The reason it may matter more than its weight-loss number
outcome: Safety
base: Phase 3 (GI-predominant)
effect: Consistent with the GLP-1 class
caveat: Class-typical GI effects; investigational

Legal status:
region: INT
status: See note
note: - Everywhere — investigational, not approved. Obesity NDA submitted to the FDA (Dec 2025); T2D filing expected 2026. A potential 2026 approval would make it the first oral small-molecule GLP-1.
- Gray market: because it is a small molecule (easier to synthesise than a peptide), unregulated "research orforglipron" copies may proliferate faster than peptide knock-offs — and are just as unapproved and unverified.
- Sport: GLP-1 agonists are not currently on the WADA Prohibited List.
- This venture: not a sellable lane — an investigational drug.

Cosmetic claims:

Note: Reference entry — NOT a sellable lane, NOT yet approved. Potentially the most consequential drug in this whole register — not because it's the strongest, but because it's the first oral small-molecule GLP-1, which could solve the class's cost-and-supply problem. NDA for obesity submitted Dec 2025. No dosing published here.
Status note: fast-moving — re-check the FDA obesity decision and T2D filing

Sources:
Eli Lilly — ACHIEVE-1 (NEJM, 2025); ATTAIN-1 (NEJM, Sept 2025); ATTAIN-MAINTAIN topline (Dec 2025); ACHIEVE-2/-5 (Oct 2025); head-to-head vs oral semaglutide.
Chugai / Lilly — preclinical pharmacology of orforglipron (OWL833 / LY3502970).
Lilly — obesity NDA submission and Commissioner's National Priority Voucher (Dec 2025).