Orforglipron Tablet

Product Overview

Orforglipron (development codes LY3502970 / OWL-833) is the world’s first approved oral non-peptide small-molecule GLP-1 receptor agonist. With a rigid polycyclic heteroaromatic scaffold, it binds allosterically to the transmembrane helical bundle pocket of the GLP-1 receptor, preferentially activating the G protein–cAMP signaling pathway while recruiting almost no β-arrestin, thereby reducing receptor desensitization. The molecule contains no peptide bonds at all, is not degraded by proteases in the gastrointestinal tract, requires no absorption enhancer for oral absorption, can be taken with or without food, and has no water restrictions.

Formulation highlights: The marketed tablet is a film-coated tablet whose core contains microcrystalline cellulose, crospovidone, copovidone (Copovidone K25-31), anhydrous sodium carbonate and magnesium stearate; the film coating contains polyvinyl alcohol, titanium dioxide, polyethylene glycol 4000 and talc, with iron oxide colorants added by strength (0.8 mg and 9 mg contain red and yellow iron oxide; 2.5 mg and 14.5 mg contain yellow iron oxide; 5.5 mg and 17.2 mg contain black and red iron oxide). Each tablet contains ≤10 mg of sodium. Strengths are labeled as orforglipron free acid, with the corresponding orforglipron calcium salt amount also stated on the label.

Relationship to other forms in the series: The CAS 2212020-52-3 on this card corresponds to orforglipron free acid; the hemicalcium salt monohydrate is 3008544-96-2. In the marketed formulation the oxadiazolone exists in the deprotonated calcium salt form, and tablet strengths are expressed as free-acid equivalents.

Technical Specifications

• Standards: CHP / USP / EP
• Specification: 30–40 (tablet intermediate / dosage form, as marked on the image; the publicly disclosed strengths of the FDA-approved tablets are 0.8, 2.5, 5.5, 9, 14.5 and 17.2 mg orforglipron, equivalent to 0.817, 2.554, 5.619, 9.194, 14.81 and 17.57 mg orforglipron calcium salt respectively)
• CAS No.: 2212020-52-3 (orforglipron free acid; hemicalcium salt monohydrate: 3008544-96-2)
• Molecular formula: C₄₈H₄₈F₂N₁₀O₅ (free acid; hemicalcium salt monohydrate: C₄₈H₄₈F₂N₁₀O₅·½Ca·H₂O)
• Molecular weight: 883.0 g/mol (PubChem, Cayman; MCE / Selleck list 882.96 / 882.97 respectively); monoisotopic mass 882.3777 Da; hemicalcium salt monohydrate 921.02 g/mol
• Appearance: Film-coated tablets, unscored, debossed on both sides — 0.8 mg pink round (approx. 6 mm, “L”/“G1”), 2.5 mg pale yellow round (approx. 6 mm, “L”/“G2”), 5.5 mg grayish-purple round (approx. 6 mm, “L”/“G3”), 9 mg pink modified oval (approx. 10×5 mm, “Lilly”/“G4”), 14.5 mg pale yellow modified oval (approx. 12×6 mm, “Lilly”/“G5”), 17.2 mg grayish-purple modified oval (approx. 12×6 mm, “Lilly”/“G6”)
• API purity (HPLC): ≥ 99.0%; the formulation is controlled for assay, content uniformity, dissolution and related substances in accordance with the general chapters of CHP / USP / EP
• Melting point: No melting point specification applies to the dosage form; neither orforglipron free acid nor its calcium salt has an official melting point recorded in CHP / USP / EP or in publicly available FDA / EMA documentation. The 268–275 °C cited in individual supplier COAs is single-source data and is not used as a release specification
• Chemical name: 3-[(1S,2S)-1-[5-[(4S)-2,2-dimethyltetrahydro-2H-pyran-4-yl]-2-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-1-methyl-1H-indazol-5-yl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl]-4-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-5-carbonyl]-1H-indol-1-yl]-2-methylcyclopropyl]-1,2,4-oxadiazol-5(4H)-one
• Chiral centers: (1S,2S) cyclopropane and two (4S) sites — four defined stereocenters in total
• API solubility: Freely soluble in DMSO, DMF and dichloromethane; soluble in methanol; orforglipron calcium salt is insoluble in water (a hygroscopic white to off-white / light brown solid)
• Dosage and administration: Oral, once daily, with or without food; swallow the tablet whole — do not split, crush or chew
• Storage: Store at room temperature 20–25 °C (short-term excursions to 15–30 °C permitted); the product is light-sensitive and must be kept in the original bottle and carton protected from light; the bottle contains a desiccant and is fitted with a child-resistant cap

Applications

• Long-term weight management (obesity / overweight): On April 1, 2026, the US FDA approved FOUNDAYO (orforglipron) film-coated tablets, in conjunction with a reduced-calorie diet and increased physical activity, for weight reduction and long-term maintenance in adults with obesity, or overweight adults with at least one weight-related comorbidity. Initiate at 0.8 mg once daily, increase to 2.5 mg after at least 30 days, then to 5.5 mg after a further 30 days; based on efficacy and tolerability the dose may be further escalated to 9 mg, 14.5 mg and 17.2 mg, with a maximum daily dose of 17.2 mg
• Type 2 diabetes (T2DM): The pivotal Phase III ACHIEVE and ATTAIN programs demonstrated dose-dependent HbA1c reduction and weight loss in T2DM and obesity populations; the labeling authorized by the UK MHRA in August 2026 already covers adults with inadequately controlled type 2 diabetes, the EMA’s committee has issued a positive opinion, and a marketing application has been submitted in China — the approved indications and status in each jurisdiction are subject to the latest official announcements
• Clinical pharmacology profile: Peak plasma concentrations are reached 4–8 hours after dosing; absolute bioavailability of the 0.8 mg dose is approximately 77%; plasma protein binding >99%; steady-state apparent volume of distribution approximately 285 L; half-life approximately 29–49 hours, supporting once-daily dosing; food has no clinically relevant effect on exposure
• Formulation development and manufacturing: For formulation and process development of oral solid dosage forms (direct compression / dry granulation + film coating), development and validation of content uniformity and dissolution methods, stability studies, packaging and light-protection strategy validation, and GMP scale-up from clinical to commercial stage with CMO / CDMO contract manufacturing; complements upstream/downstream solubilization technologies for BCS Class II poorly soluble APIs (e.g., SDD amorphous solid dispersions)

Safety notice: This product is a formulation intermediate / finished dosage form intended solely for compliant research, registration and pharmaceutical manufacturing use; it is not guidance for self-administration. The US prescribing information carries a boxed warning for thyroid C-cell tumors; it is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia syndrome type 2 (MEN 2); when co-administered with strong CYP3A4 inhibitors, the maximum dose is limited to 9 mg once daily; because it may delay gastric emptying, users of oral hormonal contraceptives should switch to a non-oral contraceptive method or add a barrier method for 30 days after initiation and after each dose escalation.

Product information: please contact us. This information is for reference only.