Orforglipron

Anti-obesity medication From Wikipedia, the free encyclopedia

Orforglipron, sold under the brand name Foundayo, is an oral, non-peptide, small-molecule GLP-1 receptor agonist developed as a weight loss drug by Eli Lilly and Company.[4] It was discovered by Chugai Pharmaceutical Co., then was licensed to Lilly in 2018.[4]

Trade namesFoundayo
Other namesLY-3502970
License data
Quick facts Clinical data, Trade names ...
Orforglipron
Above: skeletal diagram
Below: 3D representation
Clinical data
Trade namesFoundayo
Other namesLY-3502970
AHFS/Drugs.comfoundayo
License data
Routes of
administration
Oral
Drug classAntidiabetic agent
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Elimination half-life29–49 hours
Identifiers
  • 3-[(1S,2S)-1-[5-[(4S)-2,2-dimethyloxan-4-yl]-2-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-4-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carbonyl]indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
Chemical and physical data
FormulaC48H48F2N10O5
Molar mass882.974 g·mol−1
3D model (JSmol)
  • Cc1cc(-n2nc3c(c2-n2ccn(-c4ccc5c(cnn5C)c4F)c2=O)[C@H](C)N(C(=O)c2cc4cc([C@H]5CCOC(C)(C)C5)ccc4n2[C@@]2(c4noc(=O)[nH]4)C[C@@H]2C)CC3)cc(C)c1F
  • InChI=1S/C48H48F2N10O5/c1-25-18-32(19-26(2)40(25)49)60-42(58-16-15-57(46(58)63)37-11-10-36-33(41(37)50)24-51-55(36)7)39-28(4)56(14-12-34(39)53-60)43(61)38-21-31-20-29(30-13-17-64-47(5,6)23-30)8-9-35(31)59(38)48(22-27(48)3)44-52-45(62)65-54-44/h8-11,15-16,18-21,24,27-28,30H,12-14,17,22-23H2,1-7H3,(H,52,54,62)/t27-,28-,30-,48-/m0/s1
  • Key:USUWIEBBBWHKNI-KHIFEHGGSA-N
Close

Orforglipron was approved for medical use in the United States in April 2026.[5][6]

Medical uses

Orforglipron is indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition.[1]

Mechanism of action

Orforglipron is a small-molecule, partial GLP-1 receptor agonist affecting the activity of cyclic adenosine monophosphate (cAMP); its effects are similar to the actions of glucagon-like peptide-1 (GLP-1) for reducing food intake and lowering blood glucose levels.[4][7]

Clinical trials

The results of Phase I safety and Phase II ascending-dose clinical trials enrolling people with obesity or type 2 diabetes were published in 2023.[8][9]

Orforglipron has a half-life of 29 to 49 hours across the doses tested.[7]

Safety and dosing trials showed that the incidence of adverse events in orforglipron-treated participants was 62–89%, mostly from gastrointestinal discomfort (44–70% with orforglipron, 18% with placebo) having mild to moderate severity.[10] The most common side effects of orforglipon are diarrhea, nausea, upset stomach, and constipation.[4][10]

The ability of orforglipron to reduce blood sugar levels and body weight was judged favorable compared to dulaglutide.[10]

Phase III ACHIEVE-1 trial

In April 2025, results from a phase III clinical trial involving 559 people with type 2 diabetes who took an oral orforglipron pill, injectable dulaglutide or a placebo daily for 40 weeks showed that orforglipron produced a reduction of hemoglobin A1C level by 1.3 to 1.6 percentage points from a starting level of 8%.[4][11]

More than 65% of participants taking the highest dose of orforglipron achieved a reduction of hemoglobin A1C level by more than or equal to 1.5 percentage points, bringing them into the non-diabetic range as defined by the American Diabetes Association.[4] People taking the highest dose of the pill lost 8% of their weight, or around 16 lb (7.3 kg), on average after 40 weeks.[4][12] In its press release, Lilly noted that the subjects' weight loss had not yet plateaued at the time the trial concluded, and suggested that this indicated that greater weight reduction would ultimately be achieved with extended therapy.[4]

Side effects were similar to those seen with other GLP-1 agonists, and no significant liver problems were observed.[4]

References

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