Orforglipron vs tirzepatide: tirzepatide (Zepbound, Mounjaro) produced roughly twice the weight loss in its main trial: 20.9% at 72 weeks on the top dose, versus 11.2% for top-dose orforglipron (Foundayo) in ATTAIN-1.[2][1] Orforglipron’s advantages are that it is a daily pill with no food rules and costs less at its starting doses.[4][14] FDA approved Foundayo on April 1, 2026.[3]
Both drugs are made by Eli Lilly. See the orforglipron profile, the tirzepatide profile and our GLP-1 drugs hub.
Orforglipron vs tirzepatide at a glance
| Orforglipron (Foundayo) | Tirzepatide (Zepbound, Mounjaro) | |
|---|---|---|
| Approved | April 1, 2026[3] | Mounjaro 2022, Zepbound 2023 |
| Form | Daily tablet, with or without food[4] | Weekly injection[5] |
| Receptors | GLP-1 only[4] | GIP and GLP-1[5] |
| Molecule | Small molecule (not a peptide)[4] | Peptide[5] |
| Approved uses | Weight management (adults)[4] | Weight, sleep apnea (Zepbound); type 2 diabetes (Mounjaro)[5][6] |
| Main obesity trial | −11.2% at 72 weeks (ATTAIN-1)[1] | −20.9% at 72 weeks (SURMOUNT-1)[2] |
| Obesity with type 2 diabetes | −9.6% (ATTAIN-2)[7] | −14.7% (SURMOUNT-2)[8] |
| Doses | 0.8 mg up to 17.2 mg daily[4] | 2.5 mg up to 15 mg weekly[5] |
| Self-pay start | From $149/month[14] | From $299/month[15] |
How they work differently
Tirzepatide is an injected peptide that activates two gut-hormone receptors, GIP and GLP-1. It is often called a “dual agonist”.[5] Orforglipron activates only the GLP-1 receptor, the same target as semaglutide and liraglutide.[4]
The bigger practical difference is chemistry. Orforglipron is a small molecule, not a peptide, so stomach acid and enzymes do not break it down the way they would a peptide. That is why it can be swallowed as an ordinary tablet with or without food, unlike oral semaglutide, which needs an absorption enhancer and strict fasting.[4] Its half-life of roughly 29 to 49 hours suits once-daily dosing, while tirzepatide’s half-life of about 5 days suits weekly injections.[4][6]
Weight loss: ATTAIN vs SURMOUNT
No trial has compared the two directly. Their main obesity trials were similar in length and design:
| Trial | Dose | Weight change at 72 weeks | Placebo |
|---|---|---|---|
| ATTAIN-1 | Orforglipron low / middle / top dose | −7.5% / −8.4% / −11.2%[1] | −2.1% |
| SURMOUNT-1 | Tirzepatide 5 / 10 / 15 mg | −15.0% / −19.5% / −20.9%[2] | −3.1% |
| ATTAIN-2 (with diabetes) | Orforglipron top dose | −9.6%[7] | −2.5% |
| SURMOUNT-2 (with diabetes) | Tirzepatide 15 mg | −14.7%[8] | −3.2% |
In ATTAIN-1, 36.0% on the top orforglipron dose lost 15% or more and 18.4% lost 20% or more.[1] In SURMOUNT-1, 57% on tirzepatide 15 mg lost 20% or more.[2]
Type 2 diabetes: ACHIEVE vs SURPASS
Tirzepatide is approved for type 2 diabetes as Mounjaro. Orforglipron is not yet approved for diabetes in the US, but its trials are complete.[6][4]
| Trial | Who | HbA1c change | Weight change |
|---|---|---|---|
| ACHIEVE-1 (40 weeks) | Early diabetes, diet only | −1.24 to −1.48 (placebo −0.41)[9] | −4.5% to −7.6%[9] |
| SURPASS-1 (40 weeks) | Early diabetes, diet only | −1.87 to −2.07 (placebo +0.04)[10] | −7.0 to −9.5 kg[10] |
In ACHIEVE-3, orforglipron lowered HbA1c more than oral semaglutide (Rybelsus), with more stomach side effects.[13]
As of October 2026, orforglipron’s only US approval is for weight management, so for blood sugar control in type 2 diabetes, tirzepatide (as Mounjaro) is the only one of the two with an approved label.[4][6]
Switching from Zepbound to Foundayo
ATTAIN-MAINTAIN tested whether a pill could hold weight off after injections. People who had reached a weight plateau on tirzepatide were switched to orforglipron or placebo for a year:[11]
- On orforglipron: kept about 74.7% of their earlier weight loss.
- On placebo: kept about 49.2%.
The trial had no group that stayed on tirzepatide, so it cannot show whether the pill maintains weight as well as continuing the injection.[11] There is no official dose conversion; a clinician decides the starting dose.
Side effects
Both cause the typical GLP-1 stomach effects, mostly during dose increases.
- Foundayo label: nausea in 26% to 35% (placebo 10%), vomiting 13% to 24% (placebo 4%), constipation and diarrhea in about a fifth to a quarter. About 8% stopped because of side effects versus 3% on placebo. Heart rate rose 4 to 5 beats per minute.[4]
- SURMOUNT-1: side effects led 4.3% to 7.1% of people on tirzepatide to stop, versus 2.6% on placebo.[2]
- Both carry the boxed warning about thyroid C-cell tumors seen in rodents and are not for people with a personal or family history of medullary thyroid cancer or MEN 2.[4][5]
- Birth control pills: both labels advise backup contraception for a period after starting and after dose increases.[4][5]
Dosing compared
| Foundayo | Zepbound | |
|---|---|---|
| Start | 0.8 mg daily[4] | 2.5 mg weekly[5] |
| Steps | Every 30+ days: 2.5, 5.5, then optional 9, 14.5, 17.2 mg[4] | +2.5 mg every 4+ weeks[5] |
| Maximum | 17.2 mg[4] | 15 mg[5] |
| Food | With or without[4] | With or without[5] |
Trial papers report orforglipron doses as 6, 12 and 36 mg capsules; a bioequivalence study showed these match the marketed 5.5, 9 and 17.2 mg tablets.[17] A clinician sets the dose.
Practical differences day to day
Foundayo is one tablet a day, taken at any time and with or without food, with no needles.[4] If seven or more doses are missed in a row, the label says to restart at a lower dose.[4] Zepbound is one injection a week from a pen or vial, on the same day each week, and can be given with or without meals.[5] Some people find a weekly routine easier to remember; others prefer to avoid injections altogether. Both need dose increases every month or so at the start, which is when stomach side effects are most common.[4][5]
Cost and coverage
- Foundayo: at launch, Lilly’s self-pay price started at $149 a month for the lowest dose, with higher doses reported at up to $349.[14]
- Zepbound KwikPen: LillyDirect self-pay prices in 2026 were $299 (2.5 mg), $399 (5 mg), $499 (7.5 mg) and $699 (10 to 15 mg), with a savings offer bringing 7.5 mg and higher to $449 for eligible refills through December 31, 2026.[15]
- Medicare: both Foundayo and Zepbound KwikPen are included in the Medicare GLP-1 Bridge for weight management, at $50 a month for eligible people from July 2026 through December 2027.[16]
Prices checked October 2026. They change often; confirm with Lilly or your plan. See our Foundayo cost guide.
Which is right for you?
- Maximum weight loss: tirzepatide.
- No needles, no fasting rules, lower starting cost: orforglipron.
- Keeping weight off after injections: orforglipron has maintenance data, without a direct comparison to staying on the shot.[11]
For tirzepatide’s newer rival, see retatrutide vs semaglutide, and for an older daily GLP-1, see liraglutide vs semaglutide.
