Orforglipron vs tirzepatide

Orforglipron (Foundayo) is a daily pill that acts on one hormone receptor, GLP-1; tirzepatide (Zepbound, Mounjaro) is a weekly injection that acts on two, GIP and GLP-1. Both are Eli Lilly drugs and have never been compared directly, but tirzepatide’s trials report larger weight losses.

Orforglipron: Approved drugOnce daily
Tirzepatide: Approved drugOnce weekly
Head-to-head trials: None published

The short answer

Orforglipron is a small-molecule pill, not a peptide, that switches on one receptor: GLP-1, the target of a gut hormone that curbs appetite and raises insulin when blood sugar is high. Tirzepatide is a peptide that switches on GLP-1 and a second receptor, GIP, for another gut hormone that boosts insulin after meals. Orforglipron is one tablet a day, taken at any time with or without food, and is approved only for weight management, as Foundayo; tirzepatide is one injection a week, approved for weight management and sleep apnea (Zepbound) and for type 2 diabetes (Mounjaro).

No trial has compared them directly. In separate 72-week trials in adults with obesity, counting everyone randomized, the top dose of orforglipron lowered weight 11.1% vs 2.1% on placebo (ATTAIN-1) and the top dose of tirzepatide 20.9% vs 3.1% (SURMOUNT-1). The trials enrolled different people, so the gap is an estimate, not a measured difference. In ATTAIN-MAINTAIN, adults who had reached a weight plateau on tirzepatide and switched to orforglipron kept 74.7% of their weight loss over the next year, vs 49.2% of those switched to placebo.

At a glance

Field	OrforglipronFoundayo, LY3502970	TirzepatideActive ingredient in Mounjaro and Zepbound
Evidence	Approved drug	Approved drug
Class	Oral small-molecule GLP-1 receptor agonist	Dual GIP / GLP-1 receptor agonist
Approval	Approved in the US on April 1, 2026 as Foundayo tablets for weight management in adults with obesity, or overweight with a weight-related condition; it was the first new drug approved through FDA’s national priority voucher program. The UK’s MHRA authorized it in August 2026 for weight management and type 2 diabetes. Not approved for type 2 diabetes in the US as of early October 2026.	Approved in the US as Mounjaro (type 2 diabetes, including heart-risk reduction) and Zepbound (weight management and obstructive sleep apnea).
Sport (WADA 2026)	Not banned in sport	Not banned in sport
Common dose	0.8 → 17.2 mg daily	2.5 → 15 mg weekly
Frequency	Once daily	Once weekly
Cycle	Continuous	Continuous
Route	By mouth (tablet)	Subcutaneous injection
Half-life	about 29 to 49 hours Label	about 5 to 6 days Label
Typical draw	–	10 units50 mg with 2 mL, 2.5 mg
Vial sizes or form	0.8–17.2 mg tablets	5, 10, 20, 30, 40, 50, 60, 100 mg
Human studies	5 listedLargest: 3,127 people (2025)	5 listedLargest: 13,299 people (2025)
Main cautions	Boxed warning for thyroid C-cell tumors, as for other GLP-1 drugs (orforglipron doesn’t act on rat or mouse receptors, so rodent studies couldn’t test it). Not for anyone with a personal or family history of medullary thyroid carcinoma or MEN 2. Nausea, constipation, diarrhea and vomiting are common, mostly during step-ups; 10% stopped 17.2 mg because of side effects vs 3% on placebo. Pancreatitis, gallbladder disease and kidney injury from dehydration are listed risks. Tell the care team before anesthesia or sedation (aspiration risk).	Boxed warning for thyroid C-cell tumors (same as semaglutide). Can make birth-control pills less effective for 4 weeks after starting and after each dose increase. GI side effects, pancreatitis, gallbladder disease and dehydration-related kidney injury.
	Open Orforglipron	Open Tirzepatide

Doses shown are what labels, trials or community reports reference, not recommendations. Each compound’s page has the full detail and sources.

Key differences

How they work

Label

Orforglipron, a small molecule, activates only the GLP-1 receptor. Tirzepatide, a 39-amino-acid peptide, activates the GLP-1 and GIP receptors; a fatty-acid chain binds it to albumin, the main protein in blood, so it lasts long enough for weekly doses. Both reduce appetite and slow stomach emptying, most after the first doses.

How they’re taken

Label

Orforglipron: one tablet a day, any time, with or without food; 0.8 mg, then 2.5 and 5.5 mg after at least 30 days on each, and if needed 9, 14.5 or 17.2 mg. Tirzepatide: one injection a week; 2.5 mg, rising 2.5 mg after at least 4 weeks on each dose to 5, 10 or 15 mg. Half-lives: about 29 to 49 hours vs about 5 days.

Approved uses

Label

Tirzepatide: weight management and obstructive sleep apnea in adults (Zepbound), and type 2 diabetes in adults and children 10 and older, including lowering heart attack and stroke risk in high-risk adults (Mounjaro). Orforglipron: weight management in adults (Foundayo, approved April 1, 2026); approved for type 2 diabetes in the UK (August 2026) but not in the US as of early October 2026.

Weight loss in trials

Trial

Adults without diabetes, 72 weeks, counting everyone randomized: orforglipron 5.5, 9 and 17.2 mg lowered weight 7.4%, 8.3% and 11.1% vs 2.1% on placebo (ATTAIN-1); tirzepatide 5, 10 and 15 mg 15.0%, 19.5% and 20.9% vs 3.1% (SURMOUNT-1). Adults with type 2 diabetes: 9.6% on orforglipron 17.2 mg vs 2.5% (ATTAIN-2), and 14.7% on tirzepatide 15 mg vs 3.2% (SURMOUNT-2).

Blood sugar

Trial

HbA1c, a measure of average blood sugar over about 3 months, fell 1.24–1.48 points on orforglipron vs 0.41 on placebo over 40 weeks in early type 2 diabetes (ACHIEVE-1). In a similar 40-week trial, tirzepatide lowered it 1.7–1.8 points vs 0.1 on placebo (SURPASS-1, Mounjaro label). Average starting HbA1c was about 8% in both trials.

Side effects

Both cause nausea, diarrhea, vomiting and constipation, mostly during step-ups, and both carry a boxed warning for thyroid C-cell tumors. Stopping because of side effects: 5.3–10.3% on orforglipron vs 2.7% on placebo (ATTAIN-1), and 4.3–7.1% on tirzepatide vs 2.6% (SURMOUNT-1). Heart rate rose 4–5 beats per minute on orforglipron (Foundayo label) and up to 2.6 on tirzepatide (Zepbound label), vs 0.1–0.5 on placebo.

Interactions

Label

Orforglipron is cleared mainly by the liver enzyme CYP3A4: Foundayo’s label caps the dose at 9 mg with strong blockers of that enzyme, says to avoid strong drugs that speed it up, and limits simvastatin to 20 mg. Both labels warn that birth-control pills may work less well after starting and after each step up: for 30 days with orforglipron, 4 weeks with tirzepatide.

Head-to-head studies

None. No trial has randomized people to orforglipron or tirzepatide; the closest is ATTAIN-MAINTAIN, in which 205 adults who had lost weight on tirzepatide switched to orforglipron or placebo, with no group that stayed on tirzepatide.

Taking them together

Two GLP-1 drugsLabel

Orforglipron and tirzepatide both act on the GLP-1 receptor. The Wegovy and Zepbound labels say not to combine them with any other GLP-1 receptor agonist.

Source: Wegovy and Zepbound prescribing information, section 1

Open them in the stack check for sport status and one combined tracking checklist.

Questions

What is the difference between orforglipron and tirzepatide?

What happens when people switch from Zepbound to Foundayo?

One trial has tested it. In ATTAIN-MAINTAIN, 205 adults who had reached a weight plateau on tirzepatide in an earlier trial switched straight to daily orforglipron or a placebo pill. After 52 weeks they had kept 74.7% of their earlier weight loss on orforglipron vs 49.2% on placebo. No group stayed on tirzepatide, so the trial doesn’t show how switching compares with staying on the injection.

Is Foundayo as strong as Zepbound?

No trial has compared them. In separate 72-week trials of adults with obesity, counting everyone randomized, weight fell 11.1% on orforglipron 17.2 mg and 20.9% on tirzepatide 15 mg, vs 2.1% and 3.1% on placebo. The people and conditions differed, so the gap is an estimate. The practical differences: Foundayo is a daily pill kept at room temperature, with no food rules; Zepbound is a weekly injection stored in the fridge.

Can orforglipron and tirzepatide be taken together?

The stack check flags two GLP-1 drugs. Orforglipron and tirzepatide both act on the GLP-1 receptor. The Wegovy and Zepbound labels say not to combine them with any other GLP-1 receptor agonist. No published study has tested them together.

Which has more evidence in people, orforglipron or tirzepatide?

Orforglipron is approved in the US; its page lists 5 key human studies. Tirzepatide is approved in the US; its page lists 5 key human studies. They haven’t been compared directly in a published trial.

Are orforglipron and tirzepatide banned in sport?

Orforglipron and tirzepatide aren’t banned. This follows the WADA 2026 Prohibited List; athletes should confirm with their anti-doping organization.

Sources

Foundayo prescribing information, rev. 07/2026 (Eli Lilly)
Zepbound and Mounjaro prescribing information, rev. 08/2026 (Eli Lilly)
Wharton et al., orforglipron for obesity, ATTAIN-1 (NEJM 2025) PMID 40960239
Jastreboff et al., tirzepatide for obesity, SURMOUNT-1 (NEJM 2022) PMID 35658024
Rosenstock et al., orforglipron in early type 2 diabetes, ACHIEVE-1 (NEJM 2025) PMID 40544435
Aronne et al., orforglipron after tirzepatide or semaglutide, ATTAIN-MAINTAIN (Nat Med 2026) PMID 42120723
ATTAIN-MAINTAIN, orforglipron or placebo after tirzepatide or semaglutide in SURMOUNT-5: ClinicalTrials.gov registry entry NCT06584916

Each compound’s page lists its full sources: Orforglipron, Tirzepatide.

By Vial Guide editorsLast reviewed October 5, 2026

How we review

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