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Lexicon
Weight management

Orforglipron

An oral non-peptide GLP-1 agent that, unlike oral semaglutide, needs no sensitive intake rule.

1 min read 14 sources

To the product To the sources
White tablet bottle with a black TPD label for Orforglipron on a white podium, next to it a large, branched molecule model of blue and white glass spheres in a bright lab
Compound approved · in the US since 2026Lab tested in the shop

Summary

At a glance

Sources checked on 26 Oct 2026

Body weight in 72 weeks
-11.2 %

Highest level in a phase 3 trial with 3,127 adults with obesity without diabetes, placebo -2.1%2

At least 10% lighter
54.6 %

Share in the highest level after 72 weeks, 12.9% on placebo2

HbA1c in 40 weeks
-1.48 percentage points

Early type 2 diabetes, highest level, baseline 8.0%, placebo -0.411

Half-life
bis 49 hours

29 to 49 hours according to the US prescribing information, one tablet a day is enough12

Phase 3 in the registry
26 trials

10 of them completed, as of 26 Oct 202613

  • Orforglipron is not a peptide but a small molecule that activates the GLP-1 receptor. It binds there very tightly and is taken as a tablet once a day.108
  • Because it is not a peptide it needs no fasting rule: with food, uptake in studies was only about a fifth lower while half-life and onset stayed the same.912
  • In the large phase 3 obesity trial body weight fell by 7.5 to 11.2 percent over 72 weeks depending on the level, by 2.1 percent on placebo.2
  • In type 2 diabetes it clearly lowered long-term blood sugar and did better than oral semaglutide in a head-to-head trial. Gastrointestinal complaints were more frequent.14
  • Since April 2026 Orforglipron has been approved in the US for weight reduction, further applications are under review. Everything here is the state of research, not a recommendation.1211
Profile

Updated May 2026

Class
GLP-1 agonist

small molecule, oral

Use
Oral

in mg/day

Half-life
long

dosed daily

WADA
not specifically listed
Sizes
2 sizes

6mg/90tabs, 6mg/100tabs

Contents 13 sections
  1. At a glance
  2. What is Orforglipron?
  3. How it works
  4. How to take it
  5. Dosing
  6. What the research shows
  7. Research status
  8. Side effects
  9. Storage
  10. Related compounds
  11. FAQ
  12. Glossary
  13. Sources

What is Orforglipron?

Orforglipron is an oral GLP-1 receptor agonist, but unlike semaglutide not a peptide but a small molecule. That is the key difference: small molecules survive the stomach better and do not need the strict fasting rule like oral semaglutide.

Comparison

One, two or three receptors

Which receptors each compound targets and whether it is a peptide or a small molecule, as stated in the TPD lexicon. Tap a card to open its entry.

Small molecule, tablet Orforglipron GLP-1 GIP Glucagon 1 of 3 receptors
Peptide, tablet Semaglutide Oral GLP-1 GIP Glucagon 1 of 3 receptors Peptide, injection Semaglutide GLP-1 GIP Glucagon 1 of 3 receptors Dual agonist, injection Tirzepatide GLP-1 GIP Glucagon 2 of 3 receptors Triple agonist, injection Retatrutide GLP-1 GIP Glucagon 3 of 3 receptors

Simplified: more receptors does not automatically mean better, each path also brings its own effects. 1014

How it works

Orforglipron activates the same GLP-1 receptor as the GLP-1 peptides: more satiety, dampened appetite, better blood sugar control. Because it is a small molecule, absorption is more robust and intake more practical for everyday use.

Where it acts

One receptor, several organs

Tap a point or a card. Colour = receptor, grey = effect seen in trials.

  1. Brain

    Appetite dampened, binding in appetite centres shown in animal models10

    GLP-1
  2. Stomach

    Gastric emptying delayed after 4 weeks8

    GLP-1
  3. Pancreas

    Blood sugar lowered, HbA1c clearly lower in trials1

    GLP-1
  4. Body weight

    Up to 11.2 percent less in 72 weeks2

    Observed in trials
  5. Heart

    Pulse rose by up to 4.7 beats per minute on average4

    Observed in trials
  6. Liver

    Broken down mainly by the enzyme CYP3A412

    Observed in trials

Known targets10

Compound CHEMBL4446782: one described target, Agonist, direct binding, little beta-arrestin.

GLP-1 receptor
Gene
GLP1R
UniProt
P43220
ChEMBL
CHEMBL1784
Action
Agonist, direct binding, little beta-arrestin
Glass cell membrane with a receptor hollow where a blue molecule docks, a stream of light leading to a glass brain
As a small molecule Orforglipron acts on the GLP-1 receptor. Symbolic image.

How to take it

Oral, once daily. Unlike oral semaglutide, absorption is less sensitive, a strict fasting rule is not needed.

  • With some water, with or without food per instructions.
  • Once daily is enough given the long duration.
A glass of water, a white tablet bottle with a black TPD label for Orforglipron and a few white tablets on a white tray, a bowl of fruit beside them
Once a day, with or without food. Symbolic image.

Dosing

Dosing

Dosing, titration and syringe

Loading the dosing information …

  • Getting started and stepping up, drawn as a staircase
  • Units on the U-100 syringe for every step
  • How long one vial lasts

What the research shows

A phase 3 study (NEJM, 2025) tested orforglipron in early type 2 diabetes over 40 weeks: all three doses lowered long-term blood sugar markedly more than placebo. That makes orforglipron one of the most advanced oral GLP-1 agents with solid data.

Study results

What the trials measured

Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.

Body weight after 72 weeks23

Mean change in percent, two phase 3 trials with three levels each and placebo

Obesity without diabetes2 3,127 participants
Placebo -2.1%
Lowest level -7.5%
Middle level -8.4%
Highest level -11.2%
Obesity with type 2 diabetes3 1,613 participants
Placebo -2.5%
Lowest level -5.1%
Middle level -7.0%
Highest level -9.6%

Treatment-regimen analysis, so including all participants, also after stopping. With diabetes weight loss was smaller at every level, as with other GLP-1 drugs.

Long-term blood sugar after 40 weeks1

Change in HbA1c in percentage points, early type 2 diabetes without tablets, baseline 8.0%

Phase 3 trial, 559 participants1 40 weeks
Placebo -0.41 pp
Lowest level -1.24 pp
Middle level -1.47 pp
Highest level -1.48 pp

The lowest level in this trial was below the lowest level of the weight trials. At the end mean HbA1c on Orforglipron was 6.5 to 6.7 percent. There were no severe hypoglycaemias.

HbA1c after 52 weeks head to head4

Type 2 diabetes on metformin, 1,698 participants, open-label phase 3 trial, baseline 8.3%

Middle level against lower level4
Middle level -1.71 pp
Oral semaglutide, lower level -1.23 pp
Highest level against higher level4
Highest level -1.91 pp
Oral semaglutide, higher level -1.47 pp

Both Orforglipron levels were superior to both semaglutide levels. In return Orforglipron caused more gastrointestinal complaints, more discontinuations and a larger rise in pulse.

Share of previous weight loss maintained5

After 72 weeks of injected tirzepatide or semaglutide, then 52 weeks of tablet or placebo (model estimate)

Previously tirzepatide5 205 participants
Continued on Orforglipron 74.7%
Placebo 49.2%
Previously semaglutide5 171 participants
Continued on Orforglipron 79.3%
Placebo 37.6%

Counted were participants whose weight had reached a plateau on the injection. There was no arm that continued the injection and the trial ran for one year only.

Analytical balance in a glass enclosure with a small sample of fat tissue on one pan, racks of sample tubes beside it
Phase 3 in early type 2 diabetes: all doses lowered long-term blood sugar more than placebo. Symbolic image.

Research status

Where the research stands

Registered trials with status, participants and results. As of 26 Oct 2026. 13

  1. Preclinical Binding to the human GLP-1 receptor, animal models with an adapted receptor
  2. Phase 1 22 trials, 21 completed
  3. Phase 2 3 trials, 2 completed
  4. Phase 3 26 trials, 10 completed
  5. Approval in the US since 2026
24,871 participants in phase 3 Planned figures for running trials Approved: in the US since 1 April 2026 for long-term weight reduction in adults with obesity or overweight with a related condition. Applications in the EU, Japan and Canada are under review.12
Show all 29 phase 2 and 3 trials on a timelineHide timeline 12 completed 17 running 7 with results
Phase 2
Phase 3

Bar: start to primary endpoint (planned for running trials). Green = completed, blue = progress until 26 Oct 2026. Phase 1: 22 trials on safety and pharmacokinetics, not shown as bars.

Side effects

  • Mainly gastrointestinal: nausea, fullness, constipation or diarrhea, especially when dosing up.
  • A slow ease-in keeps this small.

Tolerability

Frequency compared with oral semaglutide

Out of 100 participants per group, how many had the event over 52 weeks. Comparison with oral semaglutide, no placebo.

59 of 100 Middle level
58 of 100 Highest level
37 of 100 Oral semaglutide, lower level
45 of 100 Oral semaglutide, higher level
Event Middle levelHighest levelOral semaglutide, lower levelOral semaglutide, higher level
Gastrointestinal events4 59%58%37%45%
Stopped due to adverse events4 9%10%4%5%

Values from the abstract, mostly mild to moderate complaints. In the large weight trial 5.3 to 10.3 percent stopped on Orforglipron and 2.7 percent on placebo because of adverse events.42

Storage

Store dry, cool and protected from light, out of reach of children. Keep the original container closed and mind the expiry date.

Three white tablet bottles of different sizes and a folded light blue towel on a white shelf
Dry, cool and protected from light in the closed original container. Symbolic image.

Related

Related compounds

Same receptors or a different path: all in the TPD lexicon.

Orforglipron
Semaglutide Oral GLP-1 as a peptide tablet, with a fasting rule Semaglutide Same receptor, as an injection Tirzepatide GLP-1 and GIP, as an injection Tirzepatide Oral GLP-1 and GIP, as a tablet Retatrutide Three receptors, as an injection Cagrilintide Different path: amylin Metformin (Glucophage) Different path: blood sugar tablet without GLP-1

FAQ

Common questions about Orforglipron

Short answers, each backed by the sources below.

How does Orforglipron differ from semaglutide as a tablet?

Semaglutide is a peptide and is poorly absorbed in the stomach, which is why a strict fasting rule applies. Orforglipron is a small molecule that acts on the same GLP-1 receptor. With food the absorbed amount was only about 18 to 24 percent lower in two studies, half-life and time to peak stayed the same. The US prescribing information states no clinically relevant food effect.912

Is Orforglipron approved?

Yes, in the US since 1 April 2026 for long-term weight reduction in adults with obesity or with overweight and at least one related condition. Applications were under review in the EU, Japan and Canada in 2026, also for type 2 diabetes. The approved tablets have different strengths than the capsules used in the trials, so the numbers are not directly comparable.1211

How much did weight drop in the trials?

In the phase 3 trial with 3,127 adults without diabetes weight fell by 7.5, 8.4 and 11.2 percent over 72 weeks depending on the level, by 2.1 percent on placebo. In the highest level 54.6 percent lost at least a tenth of their weight and 18.4 percent at least a fifth. With type 2 diabetes the loss was 5.1 to 9.6 percent. Waist size, systolic blood pressure and blood lipids improved.23

How does it perform in type 2 diabetes?

In early type 2 diabetes HbA1c fell by 1.24 to 1.48 percentage points over 40 weeks, by 0.41 on placebo. There were no severe hypoglycaemias. In a 52-week head-to-head trial both tested Orforglipron levels lowered HbA1c more than both levels of oral semaglutide, 1.91 against 1.47 percentage points comparing the higher levels.14

Which side effects were seen?

Mainly gastrointestinal complaints such as nausea, constipation, diarrhoea and vomiting, mostly mild to moderate and mainly during dose escalation. Compared with oral semaglutide 58 to 59 percent had such complaints against 37 to 45 percent. 9 to 10 percent stopped against 4 to 5 percent. Pulse rose by up to 4.7 beats per minute on average.4212

Why is one tablet a day enough?

Orforglipron stays in the blood for a long time. In the first human study the half-life after several weeks was 48 to 68 hours, the US prescribing information gives 29 to 49 hours. A steady level is reached after about a week. It is broken down mainly in the liver via CYP3A4, so interactions with drugs that slow down or speed up this enzyme matter.812

Does it help to keep weight off after injection therapy?

One trial tested this: people who switched to Orforglipron after 72 weeks of injected tirzepatide or semaglutide kept on average 74.7 and 79.3 percent of their previous loss after one year, 49.2 and 37.6 percent on placebo. There was no arm that continued the injection and the trial ran for one year only.5

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

Agonist
A compound that activates a receptor the way the body's own messenger does.
Beta-arrestin
Protein that switches off activated receptors and pulls them into the cell. Orforglipron hardly recruits it.
CYP3A4
Enzyme in the liver and gut that breaks down many drugs. Other drugs can slow it down or speed it up and so change the level.
Gastric emptying
How fast stomach contents move on into the gut. Slower means feeling full for longer.
GLP-1
Gut hormone released after eating. It dampens appetite, slows gastric emptying and promotes insulin release.
Half-life
The time after which only half of the compound is left in the blood.
HbA1c
Share of haemoglobin with sugar attached. It reflects average blood sugar over the past two to three months.
Peptide
Short chain of amino acids. It is easily broken down in the stomach, which is why most peptides are injected.
Placebo
Dummy preparation without active substance. Comparing against it shows what is due to the substance itself.
Small molecule
A compound much smaller than a peptide. It survives the stomach better and is easier to give as a tablet.
Trial phases
Phase 1 tests tolerability in a few people, phase 2 looks for the dose, phase 3 confirms benefit and safety in many.

Evidence

Sources

Show all 14 sourcesHide sources 11 Studies1 Trial registry2 Database checked 26 Oct 2026

Studies

  1. Early type 2 diabetes, 40 weeks (ACHIEVE-1, phase 3)

    Rosenstock et al., New England Journal of Medicine, 2025

    DOI 10.1056/NEJMoa2505669 PMID 40544435 NCT05971940
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  2. Obesity without diabetes, 72 weeks (ATTAIN-1, phase 3)

    Wharton et al., New England Journal of Medicine, 2025

    DOI 10.1056/NEJMoa2511774 PMID 40960239 NCT05869903
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  3. Obesity with type 2 diabetes, 72 weeks (ATTAIN-2, phase 3)

    Horn et al., The Lancet, 2025

    DOI 10.1016/S0140-6736(25)02165-8 PMID 41275875 NCT05872620
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  4. Head to head with oral semaglutide (ACHIEVE-3, phase 3)

    Rosenstock et al., The Lancet, 2026

    DOI 10.1016/S0140-6736(26)00202-3 PMID 41765029 NCT06045221
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  5. Keeping weight off after injection therapy (ATTAIN-MAINTAIN, phase 3b)

    Aronne et al., Nature Medicine, 2026

    DOI 10.1038/s41591-026-04386-7 PMID 42120723 NCT06584916
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  6. Obesity, dose finding over 36 weeks (phase 2)

    Wharton et al., New England Journal of Medicine, 2023

    DOI 10.1056/NEJMoa2302392 PMID 37351564 NCT05051579
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  7. Type 2 diabetes, dose finding over 26 weeks (phase 2)

    Frias et al., The Lancet, 2023

    DOI 10.1016/S0140-6736(23)01302-8 PMID 37369232 NCT05048719
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  8. First study in humans: half-life and gastric emptying (phase 1)

    Pratt et al., Diabetes, Obesity and Metabolism, 2023

    DOI 10.1111/dom.15184 PMID 37344954
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  9. Effect of food on absorption (phase 1)

    Ma et al., Diabetes Therapy, 2024

    DOI 10.1007/s13300-024-01554-1 PMID 38402332
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  10. How a small molecule activates the GLP-1 receptor

    Sloop et al., Science Translational Medicine, 2024

    DOI 10.1126/scitranslmed.adp5765 PMID 39693407
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  11. Overview of the first approval

    Shirley, Drugs, 2026

    DOI 10.1007/s40265-026-02363-5 PMID 42479349
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed

Trial registry

  1. All trials on ClinicalTrials.gov

    ClinicalTrials.gov, U.S. National Library of Medicine

    Checked 26 Oct 2026 via ClinicalTrials.gov API v2

Database

  1. US approval and prescribing information (Drugs@FDA)

    U.S. Food and Drug Administration, NDA 220934

    Checked 26 Oct 2026 via openFDA (drugsfda, label)
  2. Compound in ChEMBL

    ChEMBL, EMBL-EBI (CHEMBL4446782)

    Checked 26 Oct 2026 via ChEMBL

In the shop

Orforglipron in the catalog

Sizes, prices and shipping times are on the product page.

To the product