Orforglipron vs Tirzepatide: Pill vs Injection Compared
Orforglipron vs tirzepatide is a once-daily pill against a once-weekly shot, and no trial has tested them head to head. In the one like-for-like comparison, a 2026 BMJ network meta-analysis, weight change at one year beyond lifestyle change alone was -9.9% for orforglipron and -14.9% for tirzepatide.
Orforglipron is sold as Foundayo; tirzepatide as Zepbound and Mounjaro. They are different molecules: orforglipron acts on the GLP-1 receptor, while tirzepatide acts on both the GIP and GLP-1 receptors. Orforglipron doses are also written on two scales that must not be mixed.
Short answer
- Which lost more weight?
- Tirzepatide, in an indirect comparison: -14.9% vs -9.9% beyond lifestyle change alone at one year (BMJ 2026).
- Has a trial compared them directly?
- No. Only a switch study (ATTAIN-MAINTAIN) and network meta-analyses exist.
- The basic difference
- Orforglipron: a GLP-1 tablet taken daily. Tirzepatide: a GIP and GLP-1 injection taken weekly.
Sources: BMJ 2026 network meta-analysis; Foundayo FDA label; Zepbound FDA label
Orforglipron vs tirzepatide side by side
The two differ on almost every line of their records. This table lines up what the FDA labels, the Drugs@FDA records and the BMJ analysis say.
| Item | Orforglipron | Tirzepatide |
|---|---|---|
| Brand with an FDA label | Foundayo | Zepbound and Mounjaro |
| What it is | Small-molecule, nonpeptide GLP-1 receptor agonist | GIP receptor and GLP-1 receptor agonist |
| Form | Tablet, swallowed whole | Injection under the skin |
| How often | Once daily, with or without food | Once weekly |
| Label starting dose | 0.8 mg tablet once daily | 2.5 mg injection once weekly for 4 weeks |
| First FDA approval | 1 April 2026 (new molecular entity) | Mounjaro: 13 May 2022; Zepbound: 8 November 2023 |
| Weight vs lifestyle alone at one year (BMJ 2026) | -9.9% | -14.9% |
| Head-to-head trial | None found | None found |
Disclaimer: starting doses are label information, not a recommendation. Dose decisions belong with a licensed clinician.
Sources: Foundayo FDA label; Zepbound FDA label; Mounjaro FDA label; Drugs@FDA, Foundayo; Drugs@FDA, Zepbound; Drugs@FDA, Mounjaro; ATTAIN-1, NEJM 2025; BMJ 2026 network meta-analysis
Is orforglipron a pill form of tirzepatide?
No. Orforglipron is a different drug, not a tirzepatide pill. The New England Journal of Medicine ATTAIN-1 paper describes it as a small-molecule, nonpeptide oral GLP-1 receptor agonist, and the Foundayo label calls it a GLP-1 receptor agonist.
Tirzepatide works on two targets. The Zepbound label describes it as a GIP receptor and GLP-1 receptor agonist, given by injection under the skin. The Mounjaro label describes the same tirzepatide as a once weekly GIP receptor and GLP-1 receptor agonist.
Both now carry a weight use. The Foundayo label says it is used with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term. The Zepbound label uses the same aim for adults with obesity, or with overweight and at least one weight-related condition. Orforglipron reached the FDA later: its original application was approved on 1 April 2026 as a new molecular entity, against 8 November 2023 for Zepbound.
Sources: ATTAIN-1, NEJM 2025; Foundayo FDA label; Zepbound FDA label; Mounjaro FDA label; Drugs@FDA, Foundayo; Drugs@FDA, Zepbound
Orforglipron's two dose scales
Orforglipron numbers look different depending on the source, and mixing them causes errors. The trial papers (NEJM and Nature Medicine) use doses of 6, 12 and 36 mg. The FDA label expresses the marketed tablet from 0.8 to 17.2 mg, and presents trial data as equivalent doses of that tablet.
Every orforglipron dose on this page names its scale. On the label scale, the FDA label for Foundayo lists:
Starting dose: 0.8 mg tablet once daily. After at least 30 days, 2.5 mg once daily. After at least 30 days more, 5.5 mg once daily. The dose can then rise, at least 30 days apart, to 9 mg, 14.5 mg or 17.2 mg, based on response and tolerability. Maximum: 17.2 mg once daily.
For tirzepatide, the FDA label for Zepbound lists:
Starting dose: 2.5 mg injected under the skin once weekly for 4 weeks
Disclaimer: this is label information, not a recommendation. Dose decisions belong with a licensed clinician.
No source gives a way to convert a tirzepatide dose into an orforglipron dose. The tirzepatide dose steps are in our tirzepatide dosage guide.
Sources: ATTAIN-1, NEJM 2025; Foundayo FDA label; Zepbound FDA label
Which loses more weight, orforglipron or tirzepatide?
Tirzepatide came out ahead in the only like-for-like comparison, but it was indirect. The 2026 BMJ network meta-analysis compared each drug with lifestyle change alone at one year, pooling separate trials.
- Tirzepatide: -14.9% (95% confidence interval -16.0% to -13.9%), with moderate to high certainty evidence.
- Orforglipron: -9.9% (-12.4% to -7.5%).
- For scale: oral semaglutide -10.9%, and injected semaglutide -9.8%.
The ranges for tirzepatide and orforglipron do not overlap in this analysis. Still, no trial put the two drugs in the same study, so the gap is an estimate across trials, not a measured result. For tirzepatide against semaglutide, see tirzepatide vs semaglutide.
Sources: BMJ 2026 network meta-analysis
Do more people stop orforglipron because of side effects?
Orforglipron ranked among the drugs people most often stopped because of side effects. The BMJ analysis, with moderate to high certainty evidence, placed orforglipron among the drugs with the highest stopping rate for side effects, with naltrexone-bupropion, liraglutide, phentermine-topiramate, CagriSema and oral semaglutide.
| Drug and form | By dose | Placebo |
|---|---|---|
| Foundayo (orforglipron) tablet | 5.5 mg: 6%; 9 mg: 9%; 17.2 mg: 10% (8% overall) | 3% |
| Zepbound (tirzepatide) injection | 5 mg: 4.8%; 10 mg: 6.3%; 15 mg: 6.7% | 3.4% |
Each label rate comes from its own trials, with different people and designs, so the two rows are not a direct contest. The BMJ ranking is the comparison built for that. For the stomach effects behind most stopping on tirzepatide, see GLP-1 side effects.
Sources: BMJ 2026 network meta-analysis; Foundayo FDA label; Zepbound FDA label
Can you switch from tirzepatide to orforglipron?
One trial has tested a switch, and it found orforglipron held more of the weight loss than placebo. ATTAIN-MAINTAIN took people who had lost weight on tirzepatide (205 people) or semaglutide (171 people) in the SURMOUNT-5 study and randomized them to once-daily orforglipron or placebo.
In the tirzepatide group, among people who had reached a weight plateau, those on orforglipron kept a model-based estimate of 74.7% of their weight reduction, against 49.2% on placebo.
The authors note a limit: the trial had no group that stayed on the injection, and it lasted one year. So it cannot say whether switching holds weight as well as staying on tirzepatide. For how long people stay on tirzepatide, see how long can you stay on Zepbound.
Sources: ATTAIN-MAINTAIN, 2026
Orforglipron vs tirzepatide questions
Is orforglipron better than tirzepatide?+
No trial has tested them head to head. In the one like-for-like comparison, a 2026 BMJ network meta-analysis, weight change at one year compared with lifestyle change alone was -14.9% for tirzepatide and -9.9% for orforglipron. That is an indirect comparison across separate trials.
What med is the same as tirzepatide?+
Zepbound and Mounjaro both contain tirzepatide; the Mounjaro label calls it a once weekly GIP receptor and GLP-1 receptor agonist. Orforglipron is not the same: its trial paper describes it as a small-molecule, nonpeptide oral GLP-1 receptor agonist.
Has FDA approved tirzepatide for weight loss?+
Yes. The Zepbound label approves tirzepatide to reduce excess body weight and maintain weight reduction long term in adults with obesity, or with overweight and at least one weight-related condition. The Drugs@FDA record shows the first Zepbound approval on 8 November 2023.
Is orforglipron a pill version of tirzepatide?+
No. It is a different molecule that acts on the GLP-1 receptor only, while tirzepatide acts on both the GIP and GLP-1 receptors. No oral form of tirzepatide is approved. For more, see our tirzepatide pills vs injection guide.
Can you switch from tirzepatide to orforglipron?+
One trial tested it. ATTAIN-MAINTAIN moved 205 people who had lost weight on tirzepatide to once-daily orforglipron or placebo. Among those who had reached a weight plateau, the orforglipron group kept a model-based 74.7% of their weight reduction, against 49.2% on placebo. There was no group that stayed on the injection.
Is there a tirzepatide to orforglipron dose conversion?+
No label, trial or regulator source found gives one. The Foundayo label and the ATTAIN-MAINTAIN trial were checked and neither has a conversion table. Dose decisions belong with a licensed clinician.
More on the forms in tirzepatide pills vs injection.
Sources: BMJ 2026 network meta-analysis; Mounjaro FDA label; ATTAIN-1, NEJM 2025; Zepbound FDA label; Drugs@FDA, Zepbound; ATTAIN-MAINTAIN, 2026; Foundayo FDA label
Related guides
This guide is for educational purposes only and is not medical advice. It describes what FDA labels, FDA approval records and published studies report about orforglipron and tirzepatide. Questions about your own medicine belong with a licensed clinician.