Orforglipron — compound monograph
Oral non-peptide GLP-1 receptor partial agonist. Phase 3. The Institute assesses 2 outcomes for this compound and grades the strongest at moderate certainty.
§1Identification and status
§1.1Nomenclature
- Preferred name
- Orforglipron
- Compound class
- Oral non-peptide GLP-1 receptor partial agonist
- Assessment series
- Incretin receptor agonists
- Synonyms and codes
- LY3502970 · OWL833 · orforglipron (INN)
- Route as evaluated
- Oral once daily, without regard to food or water restriction
§1.2Chemistry
Chemical identifiers are reproduced where they are public. Where a structure has not been published the monograph records not disclosed rather than constructing one.[1]
- CAS registry number
- 2212020-52-3
- Molecular formula
- C40H43F2N9O4
- Average mass
- 751.8
- Monoisotopic mass
- 751.34
- ATC classification
- not assigned
§1.3Sequence and structural notes
Orforglipron is a non-peptide biased partial agonist that binds the GLP-1 receptor extracellular domain at a site distinct from the native peptide orthosteric pocket. Because it is not a peptide it has no sequence, requires no injection, is not subject to peptide-specific degradation routes, and is analysed by conventional small-molecule chromatography rather than by peptide mapping.
§1.4Assessment status
The Institute assesses Orforglipron across 2 indications and grades the strongest of them at moderate certainty. In confirmatory clinical development; no marketing authorisation.
Table 1. Assessed outcomes for Orforglipron, ordered by certainty. Each row links to the per-indication evidence extract.
| Indication | Effect as recorded | Certainty | Trials |
|---|---|---|---|
| Obesity and overweight in adults | −14.7 % body weight at 36 weeks with 45 mg in the phase 2 trial versus −2.3 % with placebo | Moderate | 3 |
| Type 2 diabetes mellitus | −2.1 % HbA1c at 26 weeks with 45 mg versus −0.4 % with placebo | Moderate | 3 |
| Effects are reproduced as the contributing trials reported them. Where a confidence interval is held it appears on the per-indication extract rather than in this summary table. | |||
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products. ICH Harmonised Tripartite Guideline 1999;Step 4 version. identifier not held by the Institute
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.