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Tirzepatide vs Semaglutide: Complete Comparison (2026 Data)

Regulatory status

Editorially reviewed · Last updated September 8, 2026 · How we review

Tirzepatide and semaglutide are the two most widely prescribed GLP-1 class drugs for weight loss and type 2 diabetes. Tirzepatide (sold as Mounjaro for diabetes and Zepbound for weight loss) is a dual GLP-1/GIP agonist. Semaglutide (sold as Ozempic for diabetes, Wegovy for weight loss, and Rybelsus as an oral formulation) is a GLP-1 agonist.
In SURMOUNT-5, tirzepatide produced 20.2% mean weight loss versus 13.7% with semaglutide at 72 weeks in adults without diabetes. It compared maximum tolerated weekly doses of tirzepatide 10 or 15 mg with semaglutide 1.7 or 2.4 mg. It did not test the newer Wegovy HD 7.2 mg injection or oral Wegovy.
This page compares the molecules across diabetes and weight-management evidence. For a choice between the weight-management brands, including product and access questions, read Zepbound vs Wegovy.

Side-by-Side Comparison

TirzepatideSemaglutide
Brand namesMounjaro (T2D), Zepbound (weight loss)Ozempic (T2D), Wegovy (weight loss), Rybelsus (oral)
ManufacturerEli LillyNovo Nordisk
MechanismDual agonist: GLP-1 + GIPSingle agonist: GLP-1
Molecule typeModified GIP peptide with GLP-1 activityModified GLP-1 peptide
Max dose15 mg (injection)Depends on product: Wegovy HD 7.2 mg weekly; oral Wegovy 25 mg daily
DosingOnce weekly (injection only)Once weekly (injection) or once daily (oral)
Half-life~5 days~7 days
FDA approvalsT2D (2022), Weight loss (2023)T2D (2017), Weight loss (2021), CV risk reduction (2024)
Oral optionNoYes (Rybelsus, oral Wegovy)
CV outcomes trialSURPASS-CVOT completed; Mounjaro CV indication approved Aug 2026SELECT (completed — 20% MACE reduction)

The SURMOUNT-5 Head-to-Head Trial

SURMOUNT-5 is the landmark study that directly compares tirzepatide and semaglutide. Published in The New England Journal of Medicine in 2025, it was a randomized, open-label trial in adults with obesity or overweight without diabetes.

Trial Design

  • Participants: 751 adults with BMI 30+ (or 27+ with weight-related comorbidity)
  • Duration: 72 weeks
  • Doses: Tirzepatide escalated to max 15 mg; semaglutide escalated to max 2.4 mg
  • Primary endpoint: Percent change in body weight at 72 weeks

Key Results

OutcomeTirzepatideSemaglutide
Average weight loss-20.2%-13.7%
Difference6.5 percentage points more—
Lost at least 10%81.6%60.5%
Lost at least 15%64.6%40.1%
Lost at least 20%48.4%27.3%
Lost at least 25%31.6%16.1%

What This Means

The treatment-regimen estimates include the effects of treatment discontinuation. Tirzepatide produced greater mean weight loss at the doses studied, but the result does not tell a particular patient which drug they will tolerate or respond to best. It also does not compare tirzepatide with Wegovy HD 7.2 mg.

Weight Loss Across All Major Trials

These are separate studies with different populations, doses and follow-up. SURMOUNT-1 uses the treatment-regimen estimate. The oral semaglutide 50 mg research dose in OASIS 1 is not the approved 25 mg oral Wegovy dose. Use SURMOUNT-5 for the direct comparison at its studied doses.

Swipe sideways to see every column.

DrugTrialIndicationDurationWeight Loss
Tirzepatide 15 mgSURMOUNT-1Obesity72 weeks-20.9%
TirzepatideSURMOUNT-5Obesity (head-to-head)72 weeks-20.2%
Tirzepatide 15 mgSURMOUNT-2Obesity + T2D72 weeks-14.7%
Semaglutide 2.4 mgSTEP 1Obesity68 weeks-14.9%
Semaglutide 2.4 mgSURMOUNT-5Obesity (head-to-head)72 weeks-13.7%
Semaglutide 2.4 mgSTEP 2Obesity + T2D68 weeks-9.6%
Oral semaglutide 50 mgOASIS 1Obesity68 weeks-15.1%

Diabetes Management: SURPASS vs SUSTAIN

SURPASS-2 directly compared tirzepatide 5, 10 and 15 mg with semaglutide 1 mg in adults with type 2 diabetes treated with metformin. All three tirzepatide doses produced greater HbA1c and weight reductions at 40 weeks. This was not a comparison with Ozempic 2 mg or Wegovy.

Cardiovascular evidence has also advanced. SURPASS-CVOT found tirzepatide non-inferior to dulaglutide for major cardiovascular events in people with type 2 diabetes and established cardiovascular disease. On August 28, 2026, the FDA approved Mounjaro to reduce major cardiovascular event risk in adults with type 2 diabetes at high risk. SELECT studied a different population and comparator: semaglutide versus placebo in people with established cardiovascular disease and overweight or obesity without diabetes. These trials do not establish which drug offers better heart protection head-to-head.

Side Effects and Tolerability

Side EffectTirzepatide (SURMOUNT-5)Semaglutide (SURMOUNT-5)
Nausea43.6%44.4%
Diarrhea23.5%23.4%
Vomiting15.0%21.3%
Constipation27.0%28.5%
Discontinuation (AEs)6.1%8.0%

These are SURMOUNT-5 safety-population results. Gastrointestinal events were generally mild to moderate. Nausea rates were similar; vomiting and discontinuation due to adverse events were numerically higher with semaglutide. Greater weight loss does not imply more side effects.

Hair Loss

Hair loss was reported in 8.3% of tirzepatide participants and 6.1% of semaglutide participants in SURMOUNT-5. These reports do not establish the cause of shedding in an individual or prove that a direct drug effect can be ruled out. Discuss persistent or concerning shedding with a clinician rather than assuming it is temporary.

Cost and Access

Compare the price for your prescribed product, dose and insurance plan, including maintenance treatment. A starter offer or list price is not a reliable estimate of your continuing out-of-pocket cost. Check the current Zepbound savings terms and Wegovy manufacturer coverage information.
Since July 1, 2026, eligible Medicare beneficiaries can access certain products through the Medicare GLP-1 Bridge for $50 per month. Included products are Wegovy injections and tablets, Foundayo tablets, and Zepbound KwikPen only. Eligibility and prior authorization apply; this is not universal coverage.

Oral Options

Semaglutide comes in oral products, including Rybelsus for type 2 diabetes and oral Wegovy for weight management. Tirzepatide is an injection.

Lilly’s FDA-approved oral obesity drug is Foundayo (orforglipron), a different active ingredient. It is not oral tirzepatide. Foundayo was approved on April 1, 2026 and can be taken without fasting. See What Is Foundayo?.

Where Does Retatrutide Fit?

Retatrutide remains investigational. Lilly reported 28.7% mean weight loss at 68 weeks with 12 mg in TRIUMPH-4, which enrolled adults with obesity or overweight and knee osteoarthritis without diabetes. That is the efficacy estimand; the estimate regardless of treatment adherence was 23.7%. This placebo-controlled trial cannot establish superiority over tirzepatide or semaglutide. There is no confirmed FDA approval date.
See Retatrutide vs Tirzepatide and Retatrutide vs Wegovy.

Frequently Asked Questions

Is tirzepatide better than semaglutide?

Tirzepatide produced greater average weight loss in SURMOUNT-5 and greater HbA1c reduction in SURPASS-2 at the doses studied. Those trials did not test Wegovy HD 7.2 mg or Ozempic 2 mg. Cardiovascular indications, tolerability, oral options and coverage also matter to the choice.

What is the SURMOUNT-5 trial?

SURMOUNT-5 is a randomized, open-label trial comparing maximum tolerated tirzepatide (10 or 15 mg) with semaglutide (1.7 or 2.4 mg) in adults without diabetes. Published in 2025, it showed tirzepatide produced -20.2% weight loss vs -13.7% for semaglutide at 72 weeks.

Does tirzepatide or semaglutide cause more side effects?

In SURMOUNT-5, nausea occurred in 43.6% with tirzepatide and 44.4% with semaglutide. Discontinuation due to adverse events was 6.1% versus 8.0%. Individual tolerability varies; neither result guarantees how you will feel.

Can tirzepatide cause hair loss?

Yes. SURMOUNT-5 reported hair loss in 8.3% with tirzepatide and 6.1% with semaglutide. These trial reports do not determine the cause of an individual’s hair loss.

Is there an oral tirzepatide?

There is no approved oral tirzepatide. Lilly’s oral obesity medicine, Foundayo, contains orforglipron. Semaglutide is also available in oral products; these are different medicines, not interchangeable tablet versions of tirzepatide.

Which is better for type 2 diabetes — tirzepatide or semaglutide?

Tirzepatide demonstrated superior HbA1c reduction and weight loss in the SURPASS-2 head-to-head trial against semaglutide 1 mg (Ozempic). Both are effective, but tirzepatide produced greater glucose control across all dose levels.

Sources

How we keep this honest
What this is
Educational information, not medical advice. It reports published research — it doesn’t recommend that you use, obtain, or supply anything.
Regulatory status
Tirzepatide and semaglutide are available in FDA-approved products with different indications and formulations. Retatrutide remains investigational.
Our standard
Every claim traces to a primary source. We label the strength of evidence and flag estimates as estimates — never as clinical fact.
No commercial ties
We don’t sell, supply, or link to suppliers of any medicine, and aren’t affiliated with any manufacturer.

Do not make decisions about your health without consulting a qualified healthcare provider. For trial enrolment, see ClinicalTrials.gov. More on how we review.

Grounded in primary sources
NEJMThe LancetJAMAFDAClinicalTrials.gov

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