Semaglutide vs tirzepatide

Both are approved once-weekly injections for weight and type 2 diabetes. Tirzepatide also acts on a second hormone receptor, GIP, and in the one head-to-head obesity trial it lowered weight more.

Semaglutide: Approved drugOnce weekly
Tirzepatide: Approved drugOnce weekly
Head-to-head trials: 2

The short answer

Semaglutide (Wegovy, Ozempic) activates the GLP-1 receptor. Tirzepatide (Zepbound, Mounjaro) activates both the GIP and GLP-1 receptors. Both are injected once a week, stepped up every 4 weeks as tolerated, and carry the same boxed warning for thyroid C-cell tumors.

They have been compared directly twice. In SURMOUNT-5, adults with obesity lost 20.2% of body weight on tirzepatide vs 13.7% on semaglutide over 72 weeks. In SURPASS-2, every tirzepatide dose lowered HbA1c more than semaglutide 1 mg in type 2 diabetes. Both labels now include lowering heart risk: Wegovy from the placebo-controlled SELECT trial, Mounjaro from SURPASS-CVOT, where tirzepatide matched dulaglutide, another GLP-1 drug.

At a glance

Field	SemaglutideActive ingredient in Ozempic and Wegovy	TirzepatideActive ingredient in Mounjaro and Zepbound
Evidence	Approved drug	Approved drug
Class	GLP-1 receptor agonist	Dual GIP / GLP-1 receptor agonist
Approval	Approved in the US as Wegovy (weight management, heart risk, MASH) and as Ozempic and Rybelsus (type 2 diabetes), as weekly injections and daily tablets.	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	0.25 → 2.4 mg weekly	2.5 → 15 mg weekly
Frequency	Once weekly	Once weekly
Cycle	Continuous	Continuous
Route	Subcutaneous injection	Subcutaneous injection
Half-life	about 1 week Label	about 5 to 6 days Label
Typical draw	5 units10 mg with 2 mL, 0.25 mg	10 units50 mg with 2 mL, 2.5 mg
Vial sizes or form	10, 20 mg	5, 10, 20, 30, 40, 50, 60, 100 mg
Human studies	5 listedLargest: 17,604 people (2023)	5 listedLargest: 13,299 people (2025)
Main cautions	Boxed warning for thyroid C-cell tumors. Not for anyone with a personal or family history of medullary thyroid carcinoma or MEN 2. Nausea, vomiting and constipation are common, especially after each step up. Pancreatitis, gallbladder disease, and kidney injury from dehydration are listed risks.	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 Semaglutide	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

Semaglutide is a GLP-1 receptor agonist. Tirzepatide is one molecule that activates both the GIP and GLP-1 receptors.

Weight loss in trials

Trial

Semaglutide 2.4 mg: 14.9% at 68 weeks vs 2.4% on placebo (STEP 1); 7.2 mg: 18.7% at 72 weeks (STEP UP). Tirzepatide 15 mg: 20.9% at 72 weeks vs 3.1% (SURMOUNT-1). Head to head: 20.2% vs 13.7% (SURMOUNT-5, which used semaglutide 1.7 or 2.4 mg).

Doses

Label

Semaglutide starts at 0.25 mg and reaches 2.4 mg in week 17; the Wegovy label allows 7.2 mg for weight after 4 weeks at 2.4 mg. Tirzepatide starts at 2.5 mg and rises 2.5 mg every 4 weeks to a maintenance dose of 5, 10 or 15 mg.

Half-life

Label

Semaglutide about 1 week, tirzepatide about 5 days, so both are weekly. Tirzepatide’s label allows moving the dosing day as long as doses stay at least 3 days apart.

Side effects

Label

Both cause nausea, diarrhea, vomiting and constipation, mostly during step-ups, and both list pancreatitis, gallbladder disease and dehydration-related kidney injury. Tirzepatide’s label adds that birth-control pills may work less well for 4 weeks after starting and after each increase. Semaglutide’s 7.2 mg dose brings more skin sensitivity (dysesthesia: 22% vs 6% at 2.4 mg).

Other approved uses

Label

Semaglutide: type 2 diabetes with kidney and heart protection (Ozempic), heart risk and MASH liver disease (Wegovy), and daily tablets. Tirzepatide: obstructive sleep apnea (Zepbound) and type 2 diabetes in children 10 and older (Mounjaro).

Head-to-head studies

The 2 published trials that compared them directly.

2025751 people

Weight fell 20.2% with tirzepatide vs 13.7% with semaglutide in adults with obesity without diabetes.

Design
Randomized open-label trial vs semaglutide
Dose
10 or 15 mg weekly vs semaglutide 1.7 or 2.4 mg
Length
72 weeks

Aronne et al., N Engl J Med 2025 (SURMOUNT-5), PMID 40353578
20211,879 people

HbA1c fell 2.01 to 2.30 points vs 1.86 with semaglutide 1 mg in type 2 diabetes; all tirzepatide doses were superior.

Design
Randomized open-label trial vs semaglutide
Dose
5, 10 or 15 mg weekly vs semaglutide 1 mg
Length
40 weeks

Frías et al., N Engl J Med 2021 (SURPASS-2), PMID 34170647

Taking them together

Two GLP-1 drugsLabel

Semaglutide 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 semaglutide and tirzepatide?

Which causes more weight loss, semaglutide or tirzepatide?

Tirzepatide, in the one trial that compared them directly in obesity: 20.2% vs 13.7% of body weight over 72 weeks (SURMOUNT-5, 751 adults without diabetes). That trial used semaglutide at 1.7 or 2.4 mg; the 7.2 mg dose now on the Wegovy label wasn’t part of it.

Can semaglutide and tirzepatide be taken together?

The stack check flags two GLP-1 drugs. Semaglutide 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, semaglutide or tirzepatide?

Semaglutide 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 have been compared directly in 2 trials, described on this page.

Are semaglutide and tirzepatide banned in sport?

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

Sources

Aronne et al., tirzepatide vs semaglutide for obesity, SURMOUNT-5 (NEJM 2025) PMID 40353578
Frías et al., tirzepatide vs semaglutide in type 2 diabetes, SURPASS-2 (NEJM 2021) PMID 34170647
Wilding et al., semaglutide for obesity, STEP 1 (NEJM 2021) PMID 33567185
Jastreboff et al., tirzepatide for obesity, SURMOUNT-1 (NEJM 2022) PMID 35658024
Wegovy prescribing information, rev. 06/2026 (Novo Nordisk)
Zepbound and Mounjaro prescribing information, rev. 08/2026 (Eli Lilly)

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

By Vial Guide editorsLast reviewed October 5, 2026

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